Insulin-producing cells grown in the lab could provide a possible cure for the age-long disease (diabetes).
Type 1 diabetes is an auto¬immune disease that wipes out insulin-producing pancreatic beta cells from the body and raises blood glucose to dangerously high levels. These high levels of Blood sugar level can be even fatal. Patients are being administered insulin and given other medications to maintain blood sugar level. To those who cannot maintain their blood sugar level, they are given beta-cell transplants but to tolerate beta cell transplants; patients have to take immunosuppressive drugs as well.
A report by a research group at Harvard University tells us that they used insulin-producing cells derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells to lower blood glucose levels in mice. Nowadays, many laboratories are getting rapid progress in human stem cell technology to develop those cells that are functionally equivalent to beta-cells and the other pancreatic cell types. Other groups are developing novel biomaterials to encapsulate such cells and protect them against the immune system without the need for immunosuppressant.
Major pharmaceutical companies and life sciences venture capital firms have invested more than $100 million in each of the three most prominent biotechnological industries to bring such treatments into clinical use:
- Massachusetts–based companies Semma Therapeutics
- Sigilon Therapeutics, and ViaCyte of San Diego
Researchers of UC San Francisco have transformed human stem cells into mature insulin-producing cells for the first time, a breakthrough in the effort to develop a cure for type-1 (T1) Diabetes. Replacing these cells, which are lost in patients with T1 diabetes, has long been a dream of regenerative medicine, but until now scientists had not been able to find out how to produce cells in a lab dish that work as they do in healthy adults.
What is T1 diabetes?
T1 diabetes is an autoimmune disorder that destroys the insulin-producing beta cells of the pancreas, typically in childhood. Without insulin’s ability to regulate glucose levels in the blood, spikes in blood sugar can cause severe organ damage and eventually death. The condition can be managed by taking regular shots of insulin with meals. However, people with type 1 diabetes still often experience serious health consequences like kidney failure, heart disease and stroke. Patients facing life-threatening complications of their condition may be eligible for a pancreas transplant from a deceased donor, but these are rare, and they are supposed to wait a long time.
Researchers have just made a breakthrough that might one day make these technologies obsolete, by transforming human stem cells into functional insulin-producing cells (also known as beta cells) – at least in mice.
“We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies,” explains one of the team, Matthias Hebrok from the University of California San Francisco (UCSF).
“This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”
Type-1 diabetes is characterized by a loss of insulin due to the immune system destroying cells in the pancreas – hence, type 1 diabetics need to introduce their insulin manually. Although this is a pretty good system, it’s not perfect.
Making insulin-producing cells from stem cells
Diabetes can be cured through an entire pancreas transplant or the transplantation of donor cells that produce insulin, but both of these options are limited because they rely on deceased donors. Scientists had already succeeded in turning stem cells into beta cells, but those cells remained stuck at an early stage in their maturity. That meant they weren’t responsive to blood glucose and weren’t able to secrete insulin in the right way.
Scientists at the University of California San Francisco made a breakthrough in the effort to cure diabetes mellitus type 1.
For the first time, researchers transformed human stem cells into mature insulin-producing cells, which could replace those lost in patients with the autoimmune. There is currently no known way to prevent type-1 (T1) diabetes, which destroys insulin production in the pancreas, limits glucose regulation, and results in high blood sugar levels. The condition can be managed with regular shots of insulin, but people with the disease often experience serious health complications like kidney failure, heart disease, and stroke.
“We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies,” according to Matthias Hebrok, senior author of a study published last week in the journal Nature Cell Biology.
“This is a critical step toward our goal of creating cells that could be transplanted into patients with diabetes,” Hebrok, director of the UCSF Diabetes Center, said in a statement.
Islets of Langerhans are groupings of cells that contain healthy beta cells, among others. As beta cells develop, they have to separate physically from the pancreas to form these islets.
The team artificially separated the pancreatic stem cells and regrouped them into these islet clusters. When they did this, the cells matured rapidly and become responsive to blood sugar. In fact, the islet clusters developed in ways “never before seen” in a lab. After producing these mature cells, the team transplanted them into mice. Within days, the cells were producing insulin similar to the islets in the mice. While the study has been successful in mice, it still needs to go through more rigorous testing to see if it would work for humans as well. But the research is up-and-coming. “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes,” He said.
“We’re finally able to move forward on several different fronts that were previously closed to us,” he added. “The possibilities seem endless.”
Basic research keeps elucidating new aspects of beta cells; there seem to be several subtypes, so the gold standard for duplicating the cells is not entirely clear. Today, however, there is “a handful of groups in the world that can generate a cell that looks like a beta cell,” says Hebrok, who currently acts as scientific advisor to Semma and Sigilon, and has previously advised ViaCyte. “Certainly, companies have convinced themselves that what they have achieved is good enough to go into patients.”
The stem cell reprogramming methods that the three companies use to prompt cell differentiation create a mixture of islet cells. Beta cells sit in pancreatic islets of Langerhans alongside other types of endocrine cells. Alpha cells, for example, churn out glucagon, a hormone that stimulates the conversion of glycogen into glucose in the liver and raises blood sugar. Although the companies agree on the positive potential of islet cell mixtures, they take different approaches to developing and differentiating their cells. Semma, which was launched in 2014 to commercialize the Harvard group’s work and counts Novartis among its backers, describes its cells as fully mature, meaning that they are wholly differentiated into beta or other cells before transplantation. “Our cells are virtually indistinguishable from the ones you would isolate from donors,” says Semma chief executive officer BastianoSanna
To get around the donor problem, researchers, including the team at UCSF has been working on nudging stem cells into becoming fully-functional pancreatic beta cells for the last few years. Still, there have been some issues in getting them all the way there.
“The cells we and others were producing were getting stuck at an immature stage where they weren’t able to respond adequately to blood glucose and secrete insulin properly,” Hebrok said.
“It has been a major bottleneck for the field.”
“We’re finally able to move forward on a number of different fronts that were previously closed to us,” Hebrok added. “The possibilities seem endless.”
Regardless of starting cell type, the companies say they are ready to churn out their cells in large numbers. Semma, for example, can make more islet cells in a month than can be isolated from donors in a year in the United States, Sanna says, and the company’s “pristine” cells should perform better than donor islets, which are battered by the aggressive techniques required for their isolation.
As these products, some of which have already entered clinical trials, move toward commercialization, regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency have expressed concern about the plasticity of the reprogrammed cells. All three firms subject their cells to rigorous safety testing to ensure that they don’t turn tumorigenic. Before successful trials, companies won’t know the dose of beta cells required for a functional cure, or how long such “cures” will last before needing to be boosted. There’ll be commercial challenges, too: while the companies are investing heavily to develop suitable industrial processes, all acknowledge that no organization has yet manufactured cell therapies in commercial volumes.
Nevertheless, there’s growing confidence throughout the field that these problems will be solved, and soon. “We have the islet cells now,” says Alice Tomei, a biomedical engineer at the University of Miami who directs DRI’s Islet Immuno-engineering Laboratory.
“These stem cell companies are working hard to try to get FDA clearance on the cells.”
Protecting stem cell therapies from the immune system
Whatever the type of cell being used, another major challenge is delivering cells to the patient in a package that guards against immune attack while keeping cells fully functional. Companies are pursuing two main strategies:
- Microencapsulation, where cells are immobilized individually or as small clusters, in tiny blobs of a biocompatible gel.
- Macroencapsulation, in which greater numbers of cells are put into a much larger, implantable device.
ViaCyte, which recently partnered with Johnson & Johnson, launched its first clinical trial in 2014. The trial involved a micro-encapsulation approach that packaged up the company’s partially differentiated, ESC-derived cells into a flat device called the PEC-Encapsulation. About the size of a Band-Aid, the device is implanted under the skin, where the body forms blood vessels around it. “It has a semipermeable membrane that allows the free flow of oxygen, nutrients, and glucose,” says ViaCyte’s chief executive officer, Paul Laikind. “And even proteins like insulin and glucagon can move back and forth across that membrane, but cells cannot.”
The trial showed that the device was safe, well-tolerated, and protected from the adaptive immune system—and that some cells differentiated into working islet cells. But most cells didn’t engraft effectively because a “foreign body response,” a variant of wound healing, clogged the PEC-Encap’s membrane and prevented vascularization. ViaCyte stopped the trial and partnered with W. L. Gore & Associates, the maker of Gore-Tex, to engineer a new membrane. “With this new membrane,” says Laikind, “we’re not eliminating that foreign body response, but we’re overcoming it in such a way that allows vascularization to take place.” The company expects to resume the trial in the second half of this year, provided it receives the green light from the FDA.
Semma is also developing macro¬-encapsulation methods, including a very thin device that in prototype form is about the size of a silver dollar coin. The device is “deceptively simple, but it allows us to put [in] a fully curative dose of islets,” Sanna says.
Semma is also investigating microencapsulation alternatives. At the same time, the company is advancing toward clinical trials using established transplantation techniques to administer donated cadaver cells to high-risk patients who find it particularly difficult to control their blood glucose levels. These cells are infused via the portal vein into the liver, and patients take immunosuppressive drugs to prevent rejection.
Sigilon is working on its microencapsulation technology. Launched in 2016 on the back of work by the labs of Robert Langer and Daniel Anderson at MIT, the company has created 1.5-millimeter gel-based spheres that can hold between 5,000 and 30,000 cells (Nat Med, 22:306–11, 2016). Each sphere is like a balloon, with the outside chemically modified to provide immune-protection, says Sigilon chief executive officer Rogerio Vivaldi. “The inside of the balloon is full of a gel that creates almost a kind of a matrix net where the cells reside.”
In 2018, shortly after partnering with Eli Lilly, Sigilon and collaborators published research showing that islet cells that were encapsulated in gel spheres and transplanted into macaques remained functional for four months. The company has not disclosed a time frame for a type 1 diabetes trial “but we’re moving pretty quickly,” says chief scientific officer David Moller.
To conclude, all three firms hope to extend their work to treat some of the 400 million people worldwide with type 2 diabetes, many of them eventually benefit from insulin injections. The recent endorsements from big Pharmaceutical underline the real progress in beta-cell transplants, says Aaron Kowalski, a molecular geneticist and chief executive officer at JDRF, a foundation based in New York that has funded research at ViaCyte and academic labs whose work has been tapped by Semma and Sigilon. “These companies all realize that if they don’t do it, somebody else will. It’s hard to predict exactly when, but somebody is going to make this work.”
The FDA Vs Stem Cell Treatments In The US
Stem cell therapy has become a popular type of treatment for a number of conditions, including to assist in the regeneration of injured tissue or diseases cells in the human body. This therapy is classified as regenerative medicine. Several advancements have already been made in this medical field, and many had experienced positive results when they underwent stem cell therapy to assist in the treatment of degenerative conditions.
While stem cell therapy has been proven to provide an effective protocol in the recovery of stroke, neurological issues, and even to assist in repairing the damage that was dealt by a heart attack, recent reports have caused many to view these treatments in a negative perspective. This is due to the warnings that were recently issued by the FDA. Even though some have experienced side-effects due to the use of stem cell therapy, it is important to note that there are facilities within the US that can provide professional services that help to minimize the risk of these adverse events.
The FDA On Stem Cell Therapy In The United States
The Food and Drug Administration of the United States is involved in the analyzing and approval of medications and medical procedures that may be offered to patients in the country. To date, the FDA has shown some interest in stem cell therapy, providing approval for several clinical trials that looked at how effective this treatment is in providing a regenerating effect on the impact that certain conditions has in the human body. Only one particular treatment that involves stem cell therapy has been officially approved by the Food and Drug Administration, however.
Within the last few months, we have seen several concerning publications made by the FDA regarding stem cell therapies, reducing the hope that some patients might have gained.
On the 25th of June, 2019, the FDA published a statement that described a permanent injunction that will occur with the many stem cell clinics in the country. The FDA has stated that the action taken from their side is to assist in providing a layer of protection for patients, due to the risks involved with undergoing treatments that utilize products that have not gone through any type of approval process.
The specific company that was targeted in this statement and by the actions that were taken by the FDA is known as US Stem Cell Clinic LLC. The court ruled in favor of the FDA and US government earlier in June, finding the defendants, being US Stem Cell Clinic LLC, guilty of the claims that were made against them.
An earlier publication also confirmed that the Federal court has decided to rule the misbranding of the stem cell products released by the US Stem Cell Clinics company as a violation of laws that have been implemented to protect the people of the country.
News publications have also announced that the regulations and guidelines that have now been set out by the FDA might cause a significant decline in the availability of stem cell treatments to patients in the United States. The companies that have been targeted through these particular actions that the FDA has taken are primarily those that have been marketing products that have not gone through approval phases – and these products have been found to put the patient’s health at risk.
The Role Of Stem Cell Therapy In Disease
While some companies have been found guilty of using unapproved and even misleading products on patients, promoted as stem cell therapy, it is important to consider the reality of the situation as well. Stem cell therapy often referred to simply as Cell therapy, has been proven as a successful regime in the treatment of several conditions. Many of the conditions that have shown improvement with the use of this therapy were previously considered difficult, or sometimes even impossible, to effectively treat.
By 2012, the Worldwide Network for Blood and Marrow Transplantation, also known as the WBMT, announced that a total of one million stem cell therapy procedures had been done throughout the world. This was a significant milestone, and these procedures have helped to save a countless number of lives. Just in this report, the WBMT refers back to a case of Marta, a girl from Madrid, who had received stem cell therapy at a young age. This treatment was provided to Marta after she was diagnosed with Leukemia. In 2002, Marta was able to overcome Leukemia, thanks to the cell therapy that was provided to her.
While lymphoma and leukemia are the conditions where patients most frequently seek a clinic that can perform stem cell therapy on them, there are many other conditions that are treated with this procedure today. The perfection of the therapy has led to a treatment that can assist in reducing the effects of over 70 diseases that may otherwise have a significant impact on the human body.
GSCG Expands To Cancun, Meets The Demands Of US Patients
The Global Stem Cells Group had recently announced the opening of a new office that they have decided to establish in Cancun, Mexico. The decision was driven by the increasing demand for cell therapy procedures by patients in the United States and by the fact that there is currently a lack of facilities that are able to provide these individuals with the professional and quality services needed. Doctors specializing in regenerative medicine are also having a hard time fulfilling the needs of patients who wish to consider cell therapy as a potential treatment option.
This is not the only local office that GSCG now operates in Cancun, as the company now has two facilities within this particular location. These offices include a stem cells laboratory, as well as a general medical facility.
Over the years, GSCG has become an established name in the stem cell field, providing thousands of doctors the opportunity to offer cell therapy as a treatment option for patients with degenerative diseases. The use of this therapy may assist in the regeneration of damaged and diseased tissues in the patient’s body.
Even though a previous office had established a presence for GSCG in Cancun, it should be noted that the company announced that the opening of the new office means they have now officially created a permanent presence for the brand in the area.
The GSCG’s new facility in Cancun is equipped with the latest advancements that have been made in the field and provide quality services that ensure patients have a trusted medical facility where their patients can undergo cell therapy as part of a regenerative medicine treatment plan.
At the moment, doctors who are in the field of regenerative medicine within the United States can turn to this facility to offer their patients an additional treatment option, apart from the standard pharmaceutical protocols that have been established. The stem cell laboratory can assist in the analyzing of patient data and also in the process of finding a matching donor for the person who is in need of stem cell treatment.
GSCG’s facility is able to assist with the culturing of expanded autonomous cells, as well as other types of cells that may be utilized in the process of stem cell therapy. A detailed approach is taken, considering the age of the donor, as this would also provide an overview of the autonomous stem cell age. The patient being treated is also taken into close consideration, as there are different methods of introducing these stem cells to the body for enhanced efficacy.
A more aggressive method is often needed in those patients with conditions such as autism, Alzheimer’s disease, and kidney-related conditions. Other conditions can also be treated, such as pulmonary diseases, Parkinson’s disease. In cases of a stroke, the vascular arteries, along with the carotid artery, is targeted with the therapy for a more effective approach to assisting with the regeneration of damaged structures in the patient’s brain. This ultimately leads to a significant improvement in the delivery of stem cells to the patient’s body, which could enhance the overall efficacy expressed by the treatment.
When these procedures are provided to the patient through the GSCG, an appropriate ICU unit is made available to ensure the patient is provided with adequate care during the operation and recovery of the procedure.
The utilization of recent technological advancements at laboratories facilitated by GSCG can also assist in providing a more economical approach to cell therapy. The utilization of allogenic stem cell procedures can be addressed using techniques that will essentially offer a reduction in the costs involved.
Planar technologies may be utilized when the demand is less than one billion cells per annum, which can significantly reduce the costs of the process and, in turn, make these treatments available to patients at a lower price.
The utilization of autologous stem cell transplantation also offers an opportunity for patients to undergo stem cell therapy when a sibling does not provide an ideal match. Cells can be cultivated from the bone marrow and treated with specific drugs in order to yield targeted results. In the case of malignant cells in the body, bone marrow can be treated with monoclonal antibodies or cytotoxic drugs to target such cells when transplanted back into the patient.
Appropriate storage solutions are also taken into consideration to assist with the cultivation process, and to reduce the risk of enzymatic treatment leads to the differentiation of cells into other types. The culture condition becomes crucial for the expansion of stem cells. A PA6 conditioned medium, along with an enclosure of semi-permeable hollow fiber membranes, is one example of how the laboratory can keep certain stem cells from differentiating, while also assuring successful cultivation and expansion.
The GSCG’s Role In The New FDA Warnings
The fact that the FDA has announced the warnings against stem cell therapy products and had even taken action against a relatively popular company in the United States have now caused a limitation in access to these treatments. With a seizure of the services provided by companies that have been affected by the FDA’s actions and the knowledge of the misleading marketing information that was used in the campaigns initiated by these companies, patients might not be sure where to turn to right now.
The same problem is faced by many doctors in the field of regenerative treatments and medicine. Doctors in these fields need to ensure a facility they utilize to allow patients to undergo a treatment like a cell therapy can offer a safe procedure.
This is where the GSCG comes into the bigger picture. With the establishment of a permanent presence in Mexico, doctors are now given access to a facility that has an established history for providing quality stem cell therapy services to patients with qualifying diseases. The company is not only trusted but have been performing stem cell therapy procedures on patients that had led to successful results.
These treatments may help to assist in repairing neurological problems caused by disorders like Parkinson’s disease, stroke, or an injury to the spinal cord. They may also offer new hope to people with diabetes, heart disease, and even those who had previously suffered damage to their cardiovascular system due to a heart attack.
Even though recent publications from the FDA has caused concerns to be raised regarding stem cell therapy, many patients are still interested in undergoing these treatment procedures. A significant number of studies have provided evidence on the efficacy of treating tissue damage caused by various conditions through stem cell therapy. Patients interested in undergoing stem cell treatment are now advised to turn their interest to Stem Cells Centers in Cancun and related regions, where highly specialized and experienced doctors are able to provide a professional service.
One major aims of regenerative medicine is to replace lost tissue with new cellular material or to improve the regeneration of damaged, malfunctioning, diseases tissue and organs using stem cell transplantation. In view of this, the discovery of Extracellular vesicles (EVs) in the twentieth century have being considered as significant factors in inflammation and immune responses, antigen presentation, immunomodulation, coagulation, tissue regeneration, organ repair, cell-cell communication, senescence, proliferation and differentiation in the body . Extracellular vesicles are believed to be involved in many biological processes and they can be modified to contain specific proteins, genetic lipids, and genetic materials including messenger RNA (mRNA), microRNA (mRNA), and other small non-coding RNAs, and genomic DNA (gDNA) from their progenitor cell.
Extracellular vesicles are classified into two groups which include; exosomes and ectosomes . Exosomes are characterized with cup-shaped morphology, appearred as flattened spheres with diameters ranging from 30 to 150 nm. Similarly, exosomes have a characteristic lipid bilayer which has an average thickness of ∼5 nm. . Thus, the lipid components of exosomes include ceramide (sometimes used to differentiate exosomes from lysosomes), cholesterol, sphingolipids, and phosphoglycerides with long and saturated fatty-acyl chains. The exosome is formed or derived from a multivesicular body (MVB) when the MVB fuses with the plasma membrane and is released into the extracellular environment.
Diagrammatic representation of a medium size Exosome.
Exosomes contain many types of biomolecule, including proteins, carbohydrates, lipids and nucleic acids which vary depending on the EV’s origin, its physiological and pathological state, and even the precise cellular release site. Thus, the protein composition within can also mark the existence of disease pathologies such as inflammatory diseases; however, exosomes also contain a number of common proteins as well as those that participate in vesicle formation and trafficking. Furthernore, exosome plays a role in intercellular communication by carrying proteins and RNAs between neighboring cells or even to distant organs, they also bind to cell membranes through receptor– ligand interaction and mediate antigen presentation, cancer progression etc.
Various techniques have being developed for the isolation of exosomes which includes; ultracentrifugation-based isolation techniques, size-based techniques, precipitation techniques, immune-affinity capture-based techniques, and some novel combination techniques . Exosomes primarily exist in pellets after centrifugation 100000–200000×g and the use of Ultracentrifugation and ultrafiltration can be used to obtain purified exosomes in the laboratory, but this technology is difficult to apply on a large scale .
Exosomes can be stored at 4°C for up to 1 week for short-term while it can be stored at -80°C for long-term by suspending it in phosphate buffered saline.
More importantly, growing evidence has also suggested that exosomes play a key role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes in body fluids and blood in particular are potentially non-invasive or minimally invasive biomarkers for early diagnosis and prognosis of various types of cancer. As the first step towards improving human health, exosomes have to be reliably and efficiently isolated from complex biological matrices like blood, urine, and cerebrospinal fluid since they are currently tested as next-generation biomarkers in those body fluids.
In conclusion, it is advantageous to use exosomes for cell based treatments because the use of exosomes can avoid problems associated with the transfer of cells, which may already have damaged or mutated DNA . Also, exosomes are small and can easily circulate through capillaries, whereas the cells used in other cell-based therapies, such as MSCs, are too large to go through capillaries, and thus cannot get beyond first pass capillary beds, such as the lungs.
The level of MSCs in cell-based therapies may quickly diminish after transplant while, exosomes can achieve a higher “dose” than the transplanted MSCs . Similarly, exosomes can also be utilized to tackle toxicity and immunogenicity problems resulting from such biomaterial treatments as nanoparticles .
Ø Immuno-modulatory and anti-inflammatory properties of Exosomes could be the potential biological mechanisms for clinical treatment to promote bone regeneration. 
Ø Adipose-derived stem cell-derived exosomes promote fracture healing in animals by binding to polylactic acid-glycolic acid scaffolds.
Ø Exosome can be used for the treatment of chronic kidney disease, type 1 diabetes mellitus, and skin damage .
Ø MSCs-derived exosomes have shown therapeutical benefits in stroke and intravenous administration of MSCs-derived exosomes induced an increase of neurogenesis, neurite remodeling, and angiogenesis. 
Ø Administration of MSCs-derived exosomes’ has being observed in a traumatic brain injury model by showing an inflammation reduction and good outcomes.
Ø The injection of MSCs-derived exosomes has also been shown to be a possible treatment for spinal cord injury (SCI), by reducing inflammation and by promoting neuro-regeneration in rats after injury .
Ø Exosomes can be used as a delivery system of therapeutic signals or drugs due to their low immunogenicity, ability to cross the blood-brain barrier (BBB), and long half-life in circulation.
Over the last decade, cellular therapy has developed quickly at the level of in vitro and in vivo preclinical research and in clinical trials. Thus, one of the types of adult stem cells that have provided a great amount of interest in the field of regenerative medicine due to their unique biological properties is Mesenchymal stem cells (MSCs).
Mesenchymal stem cells (MSCs) are known to be multipotent stromal cells that can differentiate into a variety of cell types which include osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue). Furthermore, MSCs are responsible for tissue repair, growth, wound healing and cell substitution resulting from physiological or pathological causes; they have various therapeutic applications such as in the treatment of central nervous system afflictions like spinal cord lesions (1). Similarly, they are characterized by an extensive capacity for self-renewal, proliferation, potential to differentiate into multiple lineages and their immune-modulatory role on various cells.
Mesenchymal stem cells have the ability to expand in many folds in culture while retaining their growth and multilineage potential. Also, they can be identified by the expression of many molecules including CD105 (SH2) CD73 and CD34, CD45. Thus, these properties of MSCs make these cells potentially ideal candidates for tissue technology.
In addition, it has been discovered that MSCs, when transplanted systemically, have the ability to transport to sites of physical harm or damage in animals, suggesting that MSCs have migratory capacity. This migration property of MSCs is important in regenerative medicine, where various injection routes are utilized depending on the damaged tissue or organ.
The first source of Mesenchymal stem cells was in the bone marrow and considered to be the gold standard for clinical research, although various other sources have being discovered which include: Adipose tissue, Dental pulp, Mobilised Peripheral blood, Amniotic fluid, Joint synovium, synovial fluid, Endosteum, Periosteum, Menstrual blood and birth-derived tissues.
Cohnheim (German Biologist) hypothesized in the late nineteenth century that fibroblastic cells derived from bone marrow were involved in wound healing throughout the body, while in 1970, Alexander Friedenstein described a population of plastic-adherent cells that emerged from long-term cultures of bone marrow and other blood-forming organs, and he showed to have colony forming capacity and osteogenic differentiation characteristics in vitro as well as in vivo upon re-transplantation.
Arnold Caplan (1991), coined the term “mesenchymal stem cell and stated that the cells as multipotent mesenchymal cell populations which can differentiate into several tissue types, and demonstrated roles for MSCs in the regeneration of bone, cartilage or ligaments in animal and clinical studies. However, the first clinical trials of MSCs were completed in 1995 when a group of 15 patients were injected with cultured MSCs to test the safety of the treatment.
According to International Society for Cellular Therapy, the proposed minimum criteria to define MSCs include the following:
(a) The cells should exhibits plastic adherence
(b) The cell should possess specific set of cell surface markers, i.e. cluster of differentiation (CD) 73, D90, CD105 and lack expression of CD14, CD34, CD45 and human leucocyte antigen-DR (HLA-DR).
(c) The cells should have the ability to differentiate in vitro into adipocyte, chondrocyte and osteoblast.
Thus, these characteristics are valid for all MSCs, although few differences exist in MSCs isolated from various tissue origins.
Mesenchymal stem/stromal cells (MSCs) can be isolated from neonatal tissues, most of which are discarded after birth, including placental tissues, fetal membranes, umbilical cord, and amniotic fluid. Placenta is an ideal starting material for the large-scale manufacture of multiple cell doses of allogeneic MSC. The placenta is a fetomaternal organ from which either fetal or maternal tissue can be isolated.
MSC derived from placenta have long-term proliferation and immunomodulatory capacity, superior to bone marrow-derived MSC. The placenta is a fetomaternal organ consisting of both fetal and maternal tissue, and thus MSC of fetal or maternal origin can be, theoretically isolated. Thus, neonatal tissues are easily available and they have biological advantages in comparison to adult sources that make them a useful source for stem cells including MSCs. They appear to be more primitive and have greater multipotentiality than their adult counterparts.
Ø MSCs have been widely used to treat immune-based disorders, such as Crohn’s disease, rheumatoid arthritis, diabetes, and multiple sclerosis.
Ø MSCs have been widely used as a treatment for numerous orthopedic diseases, including bone defects, osteoarthritis (OA), femoral head necrosis, degenerative disc, spinal cord injury, knee varus, osteogenesis imperfecta, and other systemic bone diseases.
Ø MSCs are promising cell source for treatment of autoimmune, degenerative and inflammatory diseases due to the homing ability, multilineage potential, secretion of anti-inflammatory molecules and immunoregulatory effects.
Ø MSCs play a key role in the maintenance of bone marrow homeostasis and regulate the maturation of both hematopoietic and non-hematopoietic cells.
Ø MSCs have been shown to be powerful tools in gene therapies, and can be effectively transduced with viral vectors containing a therapeutic gene, as well as with cDNA for specific proteins, expression of which is desired in a patient.
Ø It has been proved that MSCs can differentiate into insulin producing cells and have the capacity to regulate the immunomodulatory effects
- Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin. 2013 Jun; 34(6):747-54
- Friedenstein AJ, Piatetzky II S, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16:381–90
- Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974;17:331–40.
- Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.
- Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–84.
- Wang S, Qu X, Zhao RC. Clinical applications of mesenchymal stem cells. Journal ofHematology & Oncology. Apr 30, 2012;5:19.
- Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D. and Horwitz, E. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular. Therapy position statement. Cytotherapy 8, 315–317
Chronic pain. Roughly translated as a condition of persistent misery for people. It is a serious health condition that has both physical and psychological suffering and is often associated with a specific ailment like arthritis, migraine, frozen limb, etc. People who suffer from chronic pain perceive themselves to be in a state of constant agony and distress, which can affect their ability to lead a ‘normal’ life, from being able to go to work every day to social interaction.
There are several treatment options that people resort to for managing persistent pain conditions. In this article, we talk about those treatment options with the stem cell regeneration being the most current and promising one. Also, we will discuss the potential benefits and pros and cons of regenerative medicine.
What is chronic pain and how is it caused?
During ‘PAINWeek2017’ in Las Vegas, Dr. Jay Joshi, MD, explained the connection between inflammation and pain. He states that inflammation is triggered by various chemical and physical stimuli, and is a normal phenomenon of the body to protect the injured area and speed up the healing process. When inflammation exceeds its normal extent, it conversely delays the healing process and forms this cycle of non-resolving inflammation that leads to chronic pain.
Chronic pain is a multifactorial condition. It can be caused by medical harm, injury or nerve damage. However, it can also be caused by environmental factors, for example, back pain due to incorrect posture, or physiological factors such as aging, weak bones.
Common conditions that are related to chronic pain are:
- Osteoarthritis: the degeneration of cartilage in the joint and the corresponding bones, leading to pain and stiffness mainly in thumb, knee and hip joints.
- Migraine: a half-sided recurrent headache that gives a throbbing sensation and is accompanied by blurred vision and nausea.
- Multiple Sclerosis: a chronic, progressive condition that involves nerve cell sheath damage in the spinal cord and brain. Its symptoms include severe fatigue, speech disturbances, blurred vision and numbness.
- Neuropathy: a condition that involves damage to the peripheral nerves causing weakness, pain and numbness, particularly in the hands and feet.
- Fibromyalgia: a soft tissue disorder that involves widespread musculoskeletal pain also characterized by fatigue, sleep disturbance and mood swings.
According to a 2016 analysis by the National Health Interview Survey, approximately 50 million Americans suffer from chronic pain. It is considered to be one of the most common conditions that medical treatment is sought out for. Some of the repercussions of chronic pain that agonize people are:
- Depression and mood swings
- Poor performance
- Poor social life
- Restricted mobility
- Poor self-perception about life
- Dependence on opioids
Although it is necessary to diagnose and treat the underlying cause of pain, doctors deal with pain as a separate entity and provide symptomatic treatments to save patients from the continuous discomfort it brings.
Management of Chronic Pain
Some of the common management strategies adopted by doctors are:
There are several over the counter pain killers available that are widely used by patients with chronic pain. These include paracetamol, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, ibuprofen, naproxen, etc.
Although analgesics are considered safe, long term usage can produce a number of side effects. It can lead to liver damage and is specifically dangerous for patients with liver cirrhosis. Likewise, NSAIDs are known to affect the kidneys and increase the risk of a heart attack.
Drugs that are originally used to treat epilepsy can also be an effective management strategy against chronic pain. For example, the second-generation anticonvulsants Gabapentin and Lyrica are approved by FDA for the treatment of pain. First-generation anticonvulsants such as carbamazepine and phenytoin are also considered effective. However, these first-generation drugs have more side effects when compared to second-generation drugs. They can cause side effects like ataxia, liver damage, sedation, etc.
Doctors also prescribe antidepressants for the treatment of pain. These comprise of tricyclics like amitriptyline, imipramine or doxepin. These drugs can be given to patients with or without depression as it has distinct effects of pain relief and mood elevation.
Similarly, pain in fibromyalgia and diabetic nerve pain are treated with other types of antidepressants – serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine. These are equally effective as tricyclics but have comparatively milder side effects.
Opioids such as codeine, morphine, oxycodone, etc. are very effective against severe chronic pain conditions. However, these drugs are not available over the counter and not provided by the pharmacist without prescription because of their risk of addiction.
Nonetheless, experts state that if the dose is vigilantly managed, their potential benefits can outweigh the risks. That is why doctors carefully observe patients prescribed with opioids for chronic pain to avoid any untoward dependence.
If traditional medicine hasn’t worked, many people often resort to other naturally occurring remedies for its cure. Alternative medicine varies from herbal remedies and therapies that are naturally available in plants that have curative properties. Cannabinoids, Akuamma and Kratom plants are a few examples with such characteristics that are currently trending.
Could Stem Cell Regeneration (SCR) be the answer?
As the human central nervous system matures and becomes more complex, the regenerative ability of the body further reduces. Regenerative medicine caters for this by focusing on the 3 Rs; Replacement, Repair, and Restoration of tissues and their function. This can be directed for the treatment of non-resolving inflammation by generating ex vitro cells, tissues or organs which can then be transplanted into the body.
Stem cell therapy is a unique model of treatment that replaces injured or lost cells, which can help 1.5 billion people that are experiencing chronic pain worldwide, with 23-26% of the people suffering from lower backache alone. According to Dr. Jay in ‘PAINWeek2017’, there are two types of stem cell regenerative therapy: Autologous and Non-Autologous.
In autologous SCR, mesenchymal stem cells (MSCs) are derived from adipose tissue of the patient and transplanted back into the injured area, where they potentially differentiate into the respective cells. For the other type, the MSCs are derived from embryonic tissues.
Research published in Pain Physician Journal in 2017 shows that MSC therapy is a great alternative because they are readily available. In addition, their homing potential is also considered a pro and they can be grown using standard culture techniques. It has also shown that autologous SCR is potentially safe for both humans and animals.
There has been a reported reduction from pre to post-operative pain with the use of SCR. However, various complications have been acknowledged in studies. Firstly, there’s a risk of tumor formation at the site of transplantation. Secondly, there have been instances of undesired bone formation. Furthermore, there is also a risk of abnormal immune reactions to occur.
The effective results of cell-based therapy are promising, with evident results in the treatment of chronic pain conditions in osteoarthritis, degenerative disc disease as well as neuropathic pain. However, there is still a need for advanced clinical research to deepen the understanding of the mode of action of MSCs and their potential outcomes inside the human body.
As physicians, we are constantly dealing with sports injuries. While they are typically not seen as life-threatening with high chances of recovery, they could potentially cause further problems down the line for the patient. Sports injuries can also take months to heal and getting patients back on their feet can take a lot of time, effort and money, which can be frustrating for patients who want to get back to playing football every weekend or for those who have a skiing holiday booked in the next month.
Recently, there has been a massive surge in the use of stem cells as an alternative treatment to common sports injuries. This article aims to outline the benefits and risks attached to using stem cells and how this alternative treatment may help patients who are suffering from common sports injuries.
What Are The Most Common Sports Injuries?
We are constantly treating sports injuries on a regular basis. Some of the most common sports injuries doctors typically deal with are:
An ankle sprain occurs when the ligaments in the ankle are stretched and eventually torn due to twisting or falling onto the foot. Ankle sprains are common among athletes and sports enthusiasts, however, if left untreated, the ankle can weaken, making it more vulnerable to further damage. This leads to long term problems such as chronic ankle pain, arthritis, and ongoing instability.
A sprained ankle can be easily diagnosed when we see displays of swelling, bruising, stiffness and pain when we attempt to touch or move the ankle.
A groin pull is basically a groin strain. Strains occur when the muscles are overstretched, moving in directions that are not normal for them or pulled too forcefully or suddenly. This leaves them torn and damaged and results in tenderness and bruising in the groin and inner thigh area. This injury is common in athletes that play sports which require a lot of quick side-to-side movements.
A groin pull can be easily diagnosed after a thorough physical examination of the symptoms and possible tests such as x-rays and MRI’s.
A hamstring strain occurs when the three muscles in the back of the thigh are overstretched from movements such as hurdling and kicking the leg out sharply. As these muscles are naturally tight and susceptible to sprains, it can take from six to twelve months to heal and are vulnerable to recurring injuries. Poor or lack of stretching are the likely causes of a pulled hamstring.
Shin Splints is an inflammation of the muscles in the lower leg when they are overworked and stressed. Shin splints are often found in athletes that engage in sports that require a lot of running, dodging or quick stops and starts.
Knee injury: ACL tear
An ACL knee injury is a tear or sprain of the ligament that holds the leg bone to the knee. Sudden stops or changes in direction can tear the ACL and make that dreaded “pop” sound. Almost immediately, the knee will swell, feel unstable and be too painful to bear weight. This injury is common in athletes that engage in sports such as soccer, basketball, and downhill skiing.
ACL tears are commonly seen as a severe sports injury and can be traditionally treated with rehabilitation programs and surgery to strengthen or completely replace the torn ligament.
Knee injury: Patellofemoral Syndrome
Patellofemoral Syndrome occurs when repetitive movements of the kneecap (patella) are made against the thigh bone (femur) which damages the tissue. This knee pain is common among young adults and can be caused by a number of factors such as weakness in the thigh or buttock muscles, tight hamstrings, short ligaments around the kneecap or alignment problems through the feet.
Tennis Elbow (epicondylitis)
Tennis Elbow is common for athletes that play sports such as tennis or golf that require the player to ‘grip’ tightly and repetitively for an extended amount of time. This results in the ligaments of the forearm becoming strained and inflamed, making it painful to make wrist or hand motions.
What Are The Traditional Treatment Options & Management Strategies For Sports Injuries?
Traditional treatment methods and strategies for treating mild sports injuries such as sprains and strains can be done at home. Traditional advice given by doctors can include taking rest, applying ice to reduce the swelling and dressing the injury with compression bandages to support and assist healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may also be prescribed to help reduce swelling and to relieve pain.
Moderate severity injuries may be traditionally treated with immobilization strategies such as the use of crutches or a cast brace to assist the ankle to heal for the first few weeks. This may be followed with rehabilitation exercises to strengthen the ankle and prevent stiffness and future problems.
Severe sports injuries such as knee injuries are traditionally treated with surgery or rehabilitation programs to replace or restore the torn ligaments or muscles. This also goes for those patients who experience persistent problems after months of nonsurgical treatment.
Whatever the severity level of the sports injury, the healing process can take up to several months before the muscle restores to its natural condition. Injuries can also leave muscles and ligaments permanently weakened and susceptible to further injury.
Is Stem Cell Therapy An Option For Treating Sports Injuries?
The use of stem cells to treat sports injuries are becoming more popular due to its ability to grow new blood vessels that facilitate faster and better healing, decrease or prevent inflammation and release proteins (cytokines) that can slow down tissue degeneration and reduce pain. Sports injuries that include damage to tendons, ligaments, muscles, and cartilage are reported to be seeing the best results from stem cell therapy.
Dr. Bill Johnson, MD of Innovations Medical sees stem cell therapy as a revolutionary alternative to painful surgery and long recovery and states that,
“Patients who undergo stem cell therapy for their sports injury report a reduction in their painful symptoms and increase range of motion and increased mobility. Stem cell therapy helps to quickly reduce joint inflammation, and many patients see improvements in 1 to 2 days. Anti-inflammatory results of the procedure can last for 2 to 3 months and many patients see a gradual improvement in their condition over time.”
Even celebrity athletes such as Peyton Manning and Ryan Tannehill have used stem cell treatment in conjunction with traditional treatments with success. Stem cells are placed directly into the joint via surgical application or injection to aid quicker healing and promote the growth of cells needed to restore strength and flexibility in muscles and ligaments.
However, using stem cells as an alternative method to treat sports injuries is still a controversial subject and is very much still debated among medical professionals. Research is still undergoing to show whether or not stem cell therapy is the best solution. Critics of this therapy argue the fact that stem cell therapy doesn’t work any better than a placebo and that there is no clear evidence that this type of therapy is safe. Unwanted side effects can include swelling and pain and if stem cells are used from other sources or manipulated in any way, this can result in a higher risk of developing tumors.
Although a rare neurologic condition, Amyotrophic Lateral Sclerosis (ALS) is the most common type of Motor Neuron Disease (MND), a condition that affects the voluntary muscles. This is a progressive disorder that leads to muscle weakness and depletion due to nerve dysfunction.
ALS is also called Lou Gehrig’s disease, named after the football player who had this condition. The literal meaning of Amyotrophic is ‘no muscle nourishment’ which becomes the cause of muscle atrophy. ‘Lateral’ refers to the group of nerves in the spinal cord that sends signals to the muscles. It is these nerves that degenerate, leading to sclerosis in this region. In later stages, this affects the nerves that control breathing and hence can be fatal.
The initial symptoms of ALS include stiffness and muscle weakness, which gradually involves all the muscles under voluntary control. The affected regions and progressive pattern vary from one person to another. Some having difficulty holding a pen or a cup while others finding difficulty speaking, chewing or even talking. Thus, ALS is an ailment that affects daily life and makes simple tasks painful and troublesome.
According to the Center for Disease Control and Prevention (CDC), 14,500 to 15,000 people had ALS in the United States in 2016, with approximately 5000 people having a confirmed diagnosis for the condition annually. Although the average survival rate is three to five years, patients can live for ten years or more.
Are there different types of ALS?
Amyotrophic Lateral Sclerosis has two types:
Sporadic ALS: this is the most common one and affects 95% of sufferers. This type occurs without a clear cause.
Familial ALS (FALS): This type occurs in 5-10% of sufferers. This type of ALS is genetic and runs in families. This occurs due to abnormal changes to a gene that is then passed in generations.
What are the symptoms of ALS?
Early signs and symptoms might be unnoticeable and become perceptible after some time. Most clinical signs are evident of upper motor neuron and lower motor neuron lesion. The limb onset ALS (70%) involves initial symptoms in the limbs while the bulbar onset ALS (25%) is characterized by speech and swallowing problems. This is followed by weakness in the limbs later. The remaining 5% of the patients have respiratory involvement in the early period. 
Most common symptoms include:
- Muscle weakness in the limbs (distal or proximal)
- Asymmetric progressive muscle wasting
- Difficulty in motor activities like walking, talking, chewing
- Weakness in arms, legs, hands, and feet
- Muscle cramps and twitching
- Slurred speech
- Emotional liability (episodes of uncontrolled laughing and crying)
- Difficulty in maintaining posture and gait
- Difficulty in breathing and swallowing
With the progression of the disease, symptoms may spread to all parts of the body. In some patients, frontotemporal dementia may occur resulting in poor memory and decision-making abilities.
What Causes ALS?
The exact cause of ALS has not been known by scientists to date. However, research is being carried out to understand what causes ALS. There are several different factors such as:
Studies have shown that 5 to 10% of cases of ALS are caused by genetic mutations. For example, changes to the gene that makes SOD1 protein causes damage to motor neurons.
No major association has been established between environmental factors like toxins, viruses, diet or physical trauma and the risk of development of ALS. However, there is ongoing research on the subject. Studies have shown that some athletes are at a higher risk of acquiring ALS due to vigorous physical activity.
Glutamate is the neurotransmitter that is in control of signals to and from the brain. Accumulation of this neurotransmitter within the spaces surrounding the nerves damages them.
Research has also shown mitochondrial structural and functional abnormalities, as well as defects in axonal structure and transport, could be the causative agents for ALS.
How Do We Diagnosis ALS?
When it comes to diagnosis, there are no specific tests that can provide a definitive diagnosis for ALS. However, doctors conduct a series of tests to rule other similar diseases. A full medical history check and a neurologic examination are undertaken at regular intervals to assess the progressive worsening of symptoms.
Running the following Image testing diagnostic tests can help reach a diagnosis:
- Electromyography (EMG) – EMG records the electrical activity of the muscle fibers.
- Nerve Conduction Study (NCS) – NCS assesses the electrical activity of the nerves and muscles.
- Magnetic Resonance Imaging (MRI) – MRI rules out other possible conditions such as a tumor or cyst in the spinal cord, cervical spondylosis, or a hernia in the neck that could be causing the nerve compression.
Laboratory tests such as blood screening and urine tests can also be carried out so that other diseases can be eliminated.
What Are The Treatment Options & Management Strategies For ALS?
ALS is managed through a multidisciplinary approach.
Unfortunately, there is no definitive cure for the disease at this time. Management of ALS is done through symptomatic treatment to ease the condition of the patients and prevent unnecessary complications:
Support – Physicians, psychologists, speech therapists, nutritionists, and home care assistance all play a vital role in making life easier for patients with ALS.
Medication – Riluzole (Rilutek) and Edaravone (Radicava) are the drugs approved by the U.S Food and Drug Administration (FDA) for treating ALS. Riluzole is believed to reduce glutamate levels thereby, decreasing damage to the motor neurons. Edaravone acts an antioxidant and is believed to expel free radicals and reduce the oxidative stress in the motor neurons.
Lifestyle Habits – Physiotherapists can recommend exercise and physical activity like walking, swimming, and bicycling that may improve muscle strength and help elevate mood without overstressing the muscles.
Speech Therapy – therapists can help patients with ALS to employ strategies to speak clearly. They may also recommend computerized aids such as speech synthesizers and eye-tracking technology to help people learn ways for responding by nonverbal means.
Diet – Nutritionists may formulate a diet plan for patients, which consists of food that is easy to swallow and provides enough nourishment and calories for the patients to maintain adequate energy levels and to prevent excessive weight loss
Breathing Support – Patients with ALS may suffer from shortness of breath and difficulty breathing during physical activity or while lying down. If this is the case, doctors can recommend Non-Invasive Ventilation (NIV) that provides breathing support through the nose or mouth. NIV improves quality of life and increases the number of years of survival for patients.
Is Stem Cell Therapy An Option?
As previously mentioned, there is no curable treatment for ALS available. However, scientists are researching Stem Cell Therapy as the new favorable approach in the treatment of neurologic disorders.
There is a rising interest in Stem Cell Therapy as a promising remedy for curing ALS. Mesenchymal stem cells are particularly believed to be the most suitable ones due to their availability, absence of ethical issues and positive results in various experiments.
Studies and clinical trials have begun to apprehend the benefits of MSC transplantation. They demonstrate that MSCs lead to a partial recovery of motor neurons and a delay in disease progression. Also, there has been no evidence of a major adverse effect after MSC transplantation.
When testing this newfound research on animals, the lifespan of the subjected animal has increased with MSC transplantation. These positive results have encouraged the administration of MSC in ALS patients.
However, despite the safe outcomes of MSC transplantation in humans, results show that there is only a partial improvement in ALS sufferers with only a few cases that showed a delay in disease progression. Hence, there is a need for further studies and trials on a higher number of human subjects for a better understanding of MSC effects so that more significant conclusions can be reached.
The Keto Diet: A Miracle Formula Or A Dangerous Risk?
We live in a world overloaded with diets and eating plans that are all preaching miracle, long term results for weight loss and reducing risks of developing illnesses and diseases.
But, with so many different plans out there all claiming to produce the best results, it’s hard to know which one to recommend to your patients. The Paleo, the Atkins, the Pritikin Principle, the South Beach, WeightWatchers, The Zone Diet… the list goes on and on. Recently, many doctors are leaning more towards THE KETO DIET as a recommendation for not only their overweight patients; but patients that suffer from various illnesses and ailments.
WHAT IS A KETO DIET?
To put it simply, a ‘keto’ or ‘ketogenic’ diet is a low-carb, high-fat diet.
A reduction in carbohydrates puts the body into a metabolic state called ketosis. This is when the body produces small fuel molecules called ketones. Carbs are broken down into glucose and used for energy. So when someone deprives themselves of carbs, the body has no choice but to switch its fuel supply from glucose (blood sugar) to ketones found in body fat.
Therefore, as long as carbs are restricted, the body is constantly burning fat.
Kathleen M. Zelman, MPH, RD, LD told WebMD that a ketogenic diet is often used for losing weight, but it can help manage certain medical conditions such as epilepsy, heart disease, diabetes type 2, brain diseases and IBS.
WHAT ARE THE MAIN BENEFITS OF A KETO DIET?
Weight Loss & Appetite Suppression
The biggest benefit of the keto diet and the one most dieters are striving for is weight loss and suppression of appetite.
Typically, the body takes their fuel from our stores of glycogen, but with the reduction of carbohydrates in a keto diet, glucose levels are lowered and the body is forced to obtain its energy from body fat. This results in patients experiencing weight loss.
Food cravings and hunger is often the reason that our patients are failing at dieting. Another key reason why medical professionals have found the keto diet to be so successful is because of the effects it has on reducing cravings and tackling hunger.
Studies have proven that participants that follow a low-carb diet have reported a decrease in appetite and cravings compared to individuals following a low-fat diet. This is possibly down to high-fat foods slowing down the process of gastric emptying. Food that is high in fat passes through the gut at a much slower pace, leaviing the individual feeling satisfied for longer.
Diabetes Type 2
Diabetes Type 2 is triggered by spikes occurring in the patient’s blood sugar levels. Insulin is used to regulate and control these spikes. When a patient with type 2 diabetes follows a keto diet, the amount of glucose they are consuming dramatically decreases due to the lower intake of carbohydrates.
So the lower intake of glucose found in high carb food = the lower intake of insulin.
A study of 21 overweight men with type 2 diabetes who were put on a keto diet showed that most participants saw a reduction in their insulin medication or were taken off diabetes medication completely as a result of controlling their glucose levels by following a keto diet.
A keto diet has been used to treat epilepsy since the 1920s and during a recent study, seventy percent of epileptic patients have reported less and more controlled seizures and a reduction in their medication since implementing a keto diet.
Epileptic seizures occur when a network of neurons fire unexpectedly due to the overexcitement of brain cells releasing neurotransmitters, like glutamate. The brain is then not able to suppress the spread of excitability like in non-epileptic people using inhibitory neurotransmitters like gamma-aminobutyric acid, or GABA.
What a keto diet can do to control seizures is to reduce the amount of glutamate in the brain and enhance the synthesis of GABA.
Alzheimer’s Disease & Dementia
A ketogenic diet can contribute towards keeping the brain young and healthy and reduce the risk of developing degenerative brain diseases such as Alzheimer’s disease and dementia.
Findings from a study found that keto diets can protect neurovascular function against cognitive decline by clearing out beta-amyloid protein in the brain. Beta-amyloid creates toxic plaques that interfere with neuronal signaling that results in Alzheimer’s disease and dementia. Improvements to blood flow to the brain, which contributes to healthy cognitive function, were also noted.
IBS & Other Gastronomical Conditions
Fifteen percent of the general population claim to suffer from IBS. It is one of the most common complaints taken to doctors. A lot of research has been undertaken in recent years around the effect that carbohydrates have on the gastrointestinal system.
Studies have found that when sufferers consume carbohydrates, they tend to ferment in the small intestine and causes gas and bloating. For IBS sufferers, carbs are poorly absorbed by the gut wall, causing fluid to remain in the intestinal space, resulting in diarrhea.
Therefore, when IBS sufferers follow a keto diet and reduce their intake of carbohydrates, they report significant improvements to their condition.
All these amazing results from consuming low-carb, high-fat foods sounds promising, right?
Medical professions at Harvard Medical School are urging medical professionals to be wary of recommending the keto diet to their patients. They have identified numerous risks associated with following a ketogenic diet.
Not only is the body being deprived of an essential food group – carbohydrates, but a keto diet is typically high in saturated fat. High levels of saturated fat can lead to high cholesterol and heart disease.
Other risks they have been identified with following a keto diet is:
A deficiency in micronutrients including selenium, magnesium, and vitamins B and C which are found in most of the fruit and vegetables that are restricted in a keto diet.
Liver problems due to the amount of fat the body needs to metabolize. This can cause existing liver problems to worsen.
Kidney problems due to the amount of protein the body needs to metabolize. A keto diet can put strain on the kidneys and make exisitng conditions worse.
Constipation. The keto diet is low in fibrous foods like grains and legumes. The digestive system relies on a steady flow of fiber to break down foods and get rid of body waste.
“The Keto Flu” is a term for the mood swings, body aches and brain fuzz that people experience when following a keto diet. The brain needs glucose to function and when it is deprived of this, it can cause irritability and tiredness.
We want to know your thoughts and opinions on the Keto Diet!
Have you ever recommended the keto diet to your patients? Do you see the benefits happening in your patients? Is it dangerous?
JAMES P. ALLISON, PhD
Chair, department of immunology, and director.
Immunotherapy Platform, MD Anderson Cancer Center
Losing his mother to lymphoma and two uncles to melanoma and lung cancer taught James P. Alli- son, PhD, a difficult lesson at an early age. “My mother was treated with radiation and my uncle, who had lung cancer, was treated with chemotherapy. I saw the ravages of those treatments, which ultimately were unsuccessful,” he says.
Allison knew he wanted to work in cancer research, developing more effective and less toxic therapies. An undergraduate course at the University of Texas at Austin sparked his interest in T cells—warrior cells of the immune system that defend the body against infections and cancer.
In October, Allison won the 2018 Nobel Prize in Physiology or Medicine jointly with Japanese Tasuku Honjo, MD, PhD. Alison has spent more than 30 years studying how T cells work and what turns the immune system on and off against cancer. The 1980s discovered the T Cell antigen receptor, which he described as the cell’s “ignition switch.” A few years later, he showed that a molecule called CD28 acts as the “gas pedal.” Finally, he found that CTLA-4, a protein on the surface of T cells, is the “brake,” signaling the immune system to stop the millions of T cells from attacking the cancer.
The next step, he says, was to pre vent the brakes from engaging—“to give the T cells time to keep going and eliminate the tumors.” Allison’s work led to the development of drugs called checkpoint blockade antibodies, including ipilimumab (Yervoy) for melanoma. “When we started this work, the median life expectancy with metastatic melanoma was 11 months, and no drug had ever changed that,” he says. Among people treated with Yervoy, more than 20% are still alive three years later, and some have survived 10 years.
New drugs targeting another off-switch, PD-1, have since been developed to treat cancers of the head and neck, lung, kidney, and bladder, among others. Now Allison’s lab is studying different combinations of checkpoint blockades to see which patients will respond best to them. “I don’t think these approaches are going to replace any. of the traditional therapies,” he says, but, “I think that soon, immunotherapy is going to be part of every successful cancer therapy.”
However, despite the alarming rate of death from opioid overdose, this problem is not grabbing the headlines from the media for health stakeholders to pay more attention and look for ways to finding lasting solutions to the anomaly.
It is worthy to note that, while many people are addicted to opioids in the form of heroin and synthetic opioids, millions of people are out there, taking an overdose of opioids in the form of pain reliever prescription for chronic pains and other related health issues. Though, opioids are used in the treatment of chronic pain, research has suggested that they may not help relieve pain in the long-term. This has posed a serious threat to public health and economic welfare, not only for the United States but other affected countries as well.
According to the Centers for Disease Control and Prevention, the total “economic burden” of only opioid misuse prescription in the US is estimated as $78.5 billion per year, inclusive of lost productivity, criminal justice involvement, healthcare cost, and addiction treatment.
This article aims to look at how we come to this point, some facts about opioids in the United States, and some useful information about opioid overdose. Read on to uncover them all.
Opioids and Substance Abuse at a Glance.
Opiates, popularly known as narcotics, are commonly prescribed for quick pain relief and sleep inducement. Originally, it is derived from poppy plant seeds or their byproducts. Opiates occur naturally in the form of opium and morphine, but most opiates are synthetic. These drugs became highly addictive because they create an intense sense of euphoria and as well as safeness, when adding it to pain-relieving properties.
Most patients with pain disorders later turn to rely on pharmaceutical opiates like oxycodone and hydrocodone; hence, they become addicted to it. However, opioid overdose has been studied to cause a number of health problems in the users, and these health issues are not limited to serious disorders, but even death. One of the prolonged effects of opioid usages is the brain’s inability to produce endorphins naturally. Endorphins are known to be the body’s natural painkillers.
Initially, around late 1990s, when opioids were becoming popular among the people, pharmaceutical companies came out to allay the fear of the people and reassure the medical community that opiate users would not become addicted to opioids prescribed for pain relief; hence, healthcare service providers started prescribing the drugs to patients at greater rates. Subsequently, this act resulted in a extensive misuse and diversion of these drugs prior to the time it was discovered that opioid prescriptions could actually be highly addictive like other opiates.
Facts about Opioid Prescription and Misuse in America.
The rates of opioid overdose in the United States started increasing in 2017 with over 47,000 citizens died due to misuse of opioids, such as heroin, prescription opioids, illicitly manufactured fentanyl (one of the powerful opioid synthetics). In the same year, this number was estimated 1.7 million and 652,000 Americans suffered from prescription opioid pain relievers and heroin use disorder respectively. The question is, how does it start?
It all starts when the body cannot properly manage and regulate pain again. In this condition, an opiate user may become addicted to the drugs, as the drugs now used to relief their pain and at the same time, create a sense of contentment and happiness in using them. Over time, even after the pains have gone, an opiate user will require more of the substance to reach the same level of high that creates happiness and contentment which they first experienced; hence, the person is already “an opiate addict.” Withdrawing from its use makes it even worse, as their bodies begin to show some unpleasant symptoms that make the user seeking more to relieve the symptoms.
From here, opioid prescription and misuse have turned out to become a public health problem in the United States with alarming rates of death on a daily basis.
Below are some facts about the opioid crisis in the United States:
- According to WQAD Digital Team’s claim of IMS Health’s market research, the number of opioid prescriptions doctors dispensed increased from 112 million to 282 million from 1992 to 2012 respectively. However, according to IQVIA, the number has declined to 236 million in 2016 and further dropped by 10.2% in 2017.
- Centers for Disease Control and Prevention, about 68% of cases of estimated 70,200 drug overdose deaths recorded in 2017 were linked to the use of opioids. This is more than six times compared to that of 1999 (including illegal opioids such as heroin and illicitly manufactured fentanyl and prescription opioids).
- According to a review, about 21 – 29% of patients with chronic pain who take opioids prescription misuse them.
- Another study also claimed that roughly 80% of heroin users initially misused prescription opioids.
- The same study also claimed that about 8 – 12% of opiate users develop an opioid use disorder.
- According to the Centers for Disease Control and Prevention, there is a 30% increase in opioid overdoses in 45 states of the United States between July 2016 to September 2017.
- In another review, opioid overdoses were seen increasing by 70% in the Midwestern region between July 2016 to September 2017.
What is been doing about it?
With over two million opioid dependants in the United States, the U.S. Department of Health and Human Services (HHS) is making efforts to tackle the opioid crisis in America by focusing on five major areas. These include:
- Promoting and enlighten people on the use of overdose-reversing drugs.
- Giving people access to treatment and recovery therapies.
- Offering support for modern research on addiction and pain.
- Promoting public health surveillance to help people understand the epidemic better.
- Enhancing better pain management practices in the country.
In furtherance to the efforts of the U.S. Department of Health and Human Services (HHS), the National Institutes of Health (NIH)’s Director Francis S. Collins in April 2018’s National Rx Drug Abuse and Heroin Summit, announced the launch of a special program referred to HEAL (Helping to End Addiction Long-term) Initiative. HEAL is an aggressive effort set up to expedite scientific solutions to address the opioid crisis in the United States.
Just because media are not paying attention to the opioid crisis in the US does not mean things are working in the medical world. With the alarming rate of opioid overdose and an increasing number of Americans abusing prescription and becoming dependent on opioids, all hands must be on deck to find a lasting solution to the current problem. While different agencies and stakeholders are not relenting on their efforts, more medical developments and approaches are still required to achieve a good result.