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January 19, 2021

Author: Benito Novas

Mexico City Medical Congress to Showcase the Global Stem Cells Group’s Latest Innovations

Monday, 10 February 2020 by Benito Novas

The group is sponsoring the event, which will attract physicians from across the globe with an interest in longevity and anti-aging medicine

MIAMI LAKES, Florida— The Global Stem Cells Group (GSCG) is set to sponsor the XI Congreso Mundial de Medicina Antienvejecimiento y Longevidad (World Conference of Anti-Aging and Longevity Medicine) to be held in Mexico City, Mexico on February 16-18, 2020.

The medical congress is expected to attract over 450 physicians and researchers from across the world interested in anti-aging and longevity practices and medical innovations. Over 30 speakers are slated to share information with attendees on a wide range of topics on how to lead a long, healthy life and improve longevity.

The GSCG is set to share a number of its latest innovations with congress attendees, including its newly released GCell technology device. This cutting-edge tool utilizes micrograft technology to harness the natural and powerful restorative capabilities of adipose tissues. Because it is FDA compliant, the device allows physicians across the globe to continue practicing adult stem cells-based procedures.

Additional benefits of GCell technology include shorter treatment times, delivering in-office treatments in around 30 minutes with local anesthesia, as well as less fat collection compared to existing treatments (15 mL versus 50 mL). GCell technology holds exciting implications across a range of medical specialties, including orthopedics, dermatology, cosmetic gynecology, aesthetics, and hair loss.

In addition to its GCell technology, the GSCG will also feature its newest line of stem cells products derived from first-tissue exosomes. Cellgenic Flow Exosomes utilizes the latest science and research available in cellular therapies to deliver a non-surgical approach to creating regenerative responses in a broad range of treatments. The product utilizes exosomes, which replicate the signals given out by stem cells, versus actual stem cells. Exosomes play a pivotal role in cell-to-cell communication and are involved in a wide range of physiological processes. These particles transfer critical bioactive molecules such as proteins, mRNA, and miRNA between cells and regulate gene expression in recipient cells.

“The XI Congreso Mundial de Medicina Antienvejecimiento y Longevidad is one of the world’s premier events connecting physicians and researchers with today’s most innovative treatments and technologies utilizing regenerative medicine,” said Benito Novas, CEO of the GSCG. “As a worldwide leader in training, education, and innovative products in the field of regenerative medicine, the GSCG is pleased to sponsor this congress and share its exciting new portfolio of products with physicians from across the world.”

To learn more about the Global Stem Cells Group and all of the group’s latest news and innovations, visit  http://www.stemcellsgroup.com/

 

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Two Global Stem Cells Group Officials to Speak at Paraguay Conference

Thursday, 06 February 2020 by Benito Novas

The group is set to sponsor the 2nd Congress of Aesthetic Medicine and Regenerative Gynecology to be held in Paraguay 

MIAMI LAKES, Florida—The Global Stem Cells Group (GSCG) has announced its sponsorship of the 2nd Congress of Aesthetic Medicine and Regenerative Gynecology to be held on March 12-13, 2020 in Asuncion, Paraguay. The GSCG’s CEO Benito Novas and Development and Research Director Dra. Maritza Novas will each deliver key lectures during the annual medical congress, which will focus on advancements in the fields of aesthetic medicine and regenerative gynecology. 

Benito Novas serves as the GSCG’s CEO and will lead a lecture on regenerative medicine marketing strategies. His talk will give practical marketing tools and advice to physicians running their own private practices in aesthetic medicine. In addition to his role as CEO with the GSCG, Novas also serves as the Head of Public Relations for the International Society for Stem Cell Application (ISSCA) and has authored two books on marketing strategies for clinics in the regenerative medicine industry, Your Aesthetic Practice: What Your Patients Are Saying and Marketing Digital en Su Clínica Estética (https://www.thriftbooks.com/a/benito-novas/2752773/). 

Dra. Maritza Novas serves as the GSCG’s Development and Research Director as well as the US Director for the ISSCA. She will deliver the opening lecture for the congress, discussing clinical applications of regenerative medicine in the aesthetic field. Her lecture will be informed by clinical case studies demonstrating the efficacy of regenerative treatments in aesthetics. Dra. Novas is well-renowned in the field of regenerative medicine for making a profound impact on her patients through innovative treatment protocols. She has additionally trained countless doctors looking to add regenerative medicine to their practices.  

On March 14, following the conclusion of the congress, representatives from the GSCG will also offer a certification course in cellular therapy. The course is designed to help all physicians who want to add stem cells therapies based on birth tissue derived components to their practices. Attendees will learn about the latest stem cell products, such as exosomes, cord blood, and amniotic fluid. Additional topics to be covered will include how to choose the right products to treat specific conditions and details about how to handle the manufacturing process, from selecting a healthy donor through quality control and storage at the medical office. 

“The Global Stem Cells Group is pleased to serve as a sponsor for the 2nd Congress of Aesthetic Medicine and Regenerative Gynecology,” said Benito Novas. “We look forward to sharing today’s best research on marketing strategies to help regenerative medicine practices grow their success and influence as well as sharing clinical applications of stem cells treatments in aesthetic medicine. As a global leader in stem cells education, we always look forward to these events to help more physicians gain the knowledge and skills necessary to bring life-saving treatments to more patients across the globe.”  

To learn more about the Global Stem Cells Group and all of the group’s latest news and innovations, visit  http://www.stemcellsgroup.com/.

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Global Stem Cells Group to Sponsor Miami Congress on Anti-Aging and Longevity

Friday, 31 January 2020 by Benito Novas

The group will launch its innovative GCell technology and a new online course at the event, while CEO Benito Novas will lead a lecture about marketing in the regenerative medicine field 

MIAMI LAKES, Florida—The Global Stem Cells Group (GSCG) is set to sponsor the Second Intercontinental Medical Congress on Anti-Aging and Longevity (https://miami2020.semal.org/) hosted by the Spanish Society of Anti-Aging Medicine (SEMAL) and the Federation of Latin American of Anti-Aging Medicine (FISMAL). The congress will be held on February 6-9, 2020 in Miami, Florida at the Hampton Inn & Suites by Hilton Miami Brickell. 

During the event, the Global Medical Group, a subsidiary of GSCG, will launch its GCell micrograft technology, an autologous tissue suspension that boasts minimal manipulation. The product has application implications for a wide range of medical uses, including orthopedics, dermatology, cosmetic gynecology, aesthetics, and hair loss. 

GCell technology will allow physicians utilizing regenerative medicine to continue practicing adult stem cells-based procedures thanks to the product’s adherence to FDA compliance standards since the procedure does not utilize enzymes. 

GCell technology is a closed-system medical device that harnesses the natural and powerful restorative capabilities of adipose tissue. The GCell SVF (Stromal Vascular Fraction) procedure can be performed in office in around 30 minutes, while existing procedures can take up to two hours. It also utilizes only local anesthesia, and performing physicians only have to collect 15 ml of fat instead of the 50 ml required for traditional protocols.

During the congress, the GSCG will also be launching its new online stem cells course, which will benefit doctors interested in learning about the newest stem cells protocols and technologies. The course will specifically focus on stem cells protocols based on first tissue derived compounds, such as exosomes, cord blood, and amniotic fluid. 

In addition to launching GCell technology and its new course, the GSCG’s CEO and founder Benito Novas will be giving a lecture in the main room. He will be speaking to attendees about the newest challenges facing the regenerative medicine filed and what types of marketing strategies practitioners should implement to run a successful practice integrating regenerative medicine.  

“The Global Stem Cells Group is looking forward to attending the Second Intercontinental Medical Congress on Anti-Aging and Longevity to talk with attending physicians and researchers about the technological and educational advances we are making to help move the field of regenerative medicine forward,” said Novas. 

To learn more about the Global Stem Cells Group and all of the group’s latest news and innovations, visit  http://www.stemcellsgroup.com/.

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A New Medical Device, in the Management of Complex Wounds

Tuesday, 28 January 2020 by Benito Novas

Because of the complex nature of wound healing process, an injury on the skin can pose several challenges and are likely pose complications especially when they are acute. They can as well deteriorate from acute to chronic conditions which will require external intervention best understood by a specialist physician to get the area affected by the wound under normalcy.

The complexity of wound healing and research remains an ocean of knowledge that is continuously researched intensely to uncover depths of wound healing techniques and interventions. Hence, this report contains an introduction and details to the use of a new medical innovation called Gcells used primarily for the management of wounds in their different etiology.

In a case where the process of wound healing seemed difficult, Gcells proved great effects an attribute to their design and working protocol. Gcells are conditioned to work with an enriched suspension of progenitor cells that can efficiently aid tissue repair process. In this case report, two subjects were used as donors and acceptors of these micro-grafts.

Introduction

The skin is an outer layer of the body, offering protection to the underlying layers. A wound breaks this layer and inhibits the various functions as well as expose or also break the underlying layer of tissues. Repair processes are inherent and part of homeostatic processes of the body to try to restore the skin back to its normalcy in structure and in function.

The basics for the skins repair mechanism is represented by a cloth and an inflammation where vessels dilate and monocytes activate leading to breakdown of necrotic tissues. This basic process can be inhibited or delayed by a number of varying factors that lead to deteriorative transformation of acute wounds to chronic forms. But if there is no alteration in the repair process, Mesenchymal cells kickstart proliferative process and begin to repair and restructure the affected tissues starting from the base. At the same time epithelial tissues begin to grow around the wound leading to a final step of the healing process. In this final stage, remodeling of the skin structure is primary and then maturation of a scar.

These processes are efficient best in certain conditions which if affected by factors such as cardiovascular ailment, diabetes, bacterial or any other genre of infection, can inhibit these processes.

Hence, it is necessary to understand in details these processes if there is going to be development or innovation for effective healing processes. Just as stated above, during the proliferative phase of wound healing, Mesenchymal cells are the key role players. Their structure includes a Mesenchymal stem cell (MSCs), multi potent in nature and offer supportive, therapeutic and trophic functions. They are also able to release viable trophic, anti-inflammatory cytokines and anti-apoptotic molecules that offer protection during the repair of wounded skin. MSCs also possess subpopulations that are stem-like nature commonly referred to as “side population” (SP) they have been found out to be enriched in over 1000-fold of progenitor cells and multipotent stem cells and as well exist in tissues and tumors. SP exists in a variety of organs and tissues, after an original discovery to be prominent in the bone marrow of a mouse. The organs with SP include the lung, liver, brain, mammary gland and in skeletal muscles.

In other discoveries, it was discovered that they probably may also be isolated in other tissues of the body. This discovery was in an in vitro and in vivo experiment when Dental Pulp Stem Cells (DPSCs) showed capability to differentiate into osteoblasts and built a woven bone by forming an Extracellular Matrix (ECM) secreted by the osteoblasts. The experiment drew results on the both the quality and quantity of the matrix formed by the DPSCs in the in vivo and in vitro experiment using Stem cells and accompanying biomaterials.

Thus proved that dental pulp holds potentialities of therapeutic strength and a rich source of progenitor/autologous cells that can be used to aid healing processes even applicable to regeneration of craniofacial bones.

This is the evidence that supports the working principle of Gcells innovation. Gcell successfully separates this side population with a size of 50 micron. At this cell population, they can form autologous micro-grafts and can either be used alone or alongside biomaterials prepared in a biocomplex ready for use when necessary.

In this case report, two subjects were used as donors and acceptors of these micro-grafts for enhanced healing of complex wounds through autologous micro-grafts using the Gcell.

Clinical case 1

The first case involves a woman at age 50 who does not have any diseases or disorders. She underwent a laparoscopic gastric bypass surgery and was doing well considering parameters of weightloss. Two years later she moved in for abdominoplasty bariatric. Later on, post complications showed preeminence of necrosis which was discovered after first medical examination were about 150 to 200cm2 at the end of the flaps. An initial necrosectomy showed an intense loss of tissue and we furthered to place the wound on VAC therapy and the patient in active participation of this therapy for one week then at home as an outpatient.

As an outpatient, there was improved and progressive wound cleansing while granulated tissues around the base area were cleared.

The VAC therapy after 2 months still left the margins of the wound deteriorated and surrounding areas not in axis with skin surface.

The Gcell protocol kickstarted after consent from the outpatient. We started by collecting a 3 cm2 skin sample from the patient for the purpose of obtaining the cell suspension needed to be injected to the granulation tissue (figure2).

We followed up with conventional wound treatment as in cleaning and replacement with sterile gauze dabbed with Vaseline. The wound area began to improve in both healing progress and general appearance. In two months, the undermined area disappeared as well as leveled to the axis of the skin surface. 2 months later, the wound reduced to a very little scar that is mild and smoothed compared to the initial condition. (figure 3).

A man who suffered liver cirrhosis, hiatal hernia and diabetic as well at the age of 78. Complex surgery was carried out and distal esophagectomy was performed. But hiatal hernia was not decreased into the abdomen, so he was booked up for corrective surgery. During the intervention the adhesions correlated to the previous abdominal operation and led to opening the colon for resection. Some postoperative complications by the appearance of entero-cutaneous fistulas, related to a colonic anastomosis dehiscence. A second intervention was inevitable hence a ileostomy protection and repackaging of colonic anastomosis. We closed the laparotomy using a biological prosthesis. But we met further complications from ascetic failure that needed intensive care hepatology.

Patient’s condition that included poor liver synthesis had its toll on the healing of the surgical wound. Just as the first case, necrotic tissues grew around the biological prosthesis. We conducted necrosectomy and the biological prosthesis was left half exposed. (Figure 5).

Further treatment of the wound using advanced medication helped cover the biological prosthesis with granulation tissue (figure 6).

Plastic surgeons conducted evaluations on the patient and the choice to do a rotation flap did not seem so appropriate. VAC therapy was used on the wound for about 15 days even though the device wasn’t efficient enough to maintain supposed suction in the presence of ileostomy. We proceeded to treat the patient further with Gcell protocol when wound dimension progressed to about 250cm2. The tissue granulation was of right margin near the ileostomy improved even though it appeared to be undermined.

In summary, Gcell protocol has proved a great level of efficiency in healing and restoration of damaged tissues. This progress is certain to open way for employment in the clinical practice that involves the treatment and management of acute and chronic wounds and in any other field of medicine that will inevitably need an instrument to repair lesion on tissues.

Discussion and conclusion

We made it clear earlier in this document about the efficiency of Gcell protocol in its aid to wound healing especially for wounds that are likely to develop from acute to chronic conditions. The working principle for the Gcell used to obtain the viable progenitor cells used for the micrografts relies on one individual as both the donor and the acceptor. This will help to reduce complications that are related to implants or injected micrografts that are non-autologous. Gcell is flexible and can be used both during in operating rooms as well as in ambulatories. This innovation is vastly spreading and currently used in the fields of oral-maxillo-facial field proven by recent studies even though a greater area of its application widespread and acceptable in plastic surgery, dermatology and orthopedics.

Conclusion of this report brings to clarity in demonstration, an efficient, useful and low-risk innovation in the field of medicine, useful for areas in wound management and healing. However, the viability of the Gcell product still needs to be texted on subjects with different conditions and perspectives. But we assure that this device will prove to be a better therapeutic approach in the field of medicine in improving healing of complex wounds. This confidence lies in the excellent features and working principles of this device in obtaining cell suspension, flexibility, facility for procedure and more importantly, the cost. This will help reduce the use of exorbitantly prices devices for advanced medication.
In summary, apart from introducing an efficient innovation in the medicine. Gcell has the potentialities to offer employment on clinical procedures that will help aid in the management of wounds no matter how the case may be.

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Global Stem Cells Group Enters Training Agreement with Moroccan Hospital

Friday, 24 January 2020 by Benito Novas

The agreement between Global and CHU Mohammed VI in Marrakech will help enhance staff preparation and clinical offerings in regenerative medicine

MIAMI LAKES, Florida— Stem Cells Training Inc., a subsidiary of the Global Stem Cells Group (GSCG), has announced that it has signed an onsite training agreement with Centre Hospitalo-Universitaire Mohammed VI Marrakech (CHU). GSCG faculty will travel to Marrakech, Morocco to provide this invaluable two-day training to CHU’s staff on February 14 and 15, 2020. 

The agreement names the GSCG as CHU’s provider of training for the facility’s regenerative medicine staff. Through the deal, the GSCG will provide preparation and education in the latest regenerative medicine techniques and stem cells protocols, focusing on those utilizing adult stem cells and birth tissue derived from stem cells. In addition to on-site training, the agreement also names the GSCG as CHU’s provider for all necessary equipment to implement regenerative medicine treatments. 

The additional training and supplies offered through the agreement will allow CHU to incorporate the industry’s most effective stem cells protocols into the hospital’s treatment options. 

The Centre Hospitalo-Universitaire Mohammed VI is a regional leader in quality patient care, student education, physician training, and innovative medical research. Located in Marrakech, CHU provides the bustling city with short-, medium-, and long-range care solutions. Counted among its innovative institutional projects, CHU’s Culture and Health program is committed to making the hospital a more human environment for patients seeking care.

“The agreement between the Global Stem Cells Group and the Centre Hospitalo-Universitaire Mohammed VI Marrakech is an important one for both partners,” said Benito Novas, CEO of the Global Stem Cells Group. “As a university institution, CHU is interested in leading clinical trials to prove the safety and efficacy of regenerative medicine treatment protocols—something the GSCG has a vested interest in. This agreement will allow us to train hospital staff to offer cutting-edge treatments to patients in Morocco while helping stem cells treatments gain more traction globally, making them more viable options for physicians to incorporate into their practices.” 

With the newly signed agreement, the GSCG continues to advance its mission to expand its presence across the global, especially focusing on North America and the Middle East. Physicians looking to grow their practices by offering regenerative medicine treatments can benefit from the GSCG’s trainings, which are conveniently held onsite at physicians’ home facilities, no matter where they are located globally. 

To learn more about the onsite training opportunities offered by the Global Stem Cells Group, visit https://www.stemcelltraining.net/onsitetraining/. To learn more about the Centre Hospitalo-Universitaire Mohammed VI Marrakech, visit  www.chumarrakech.ma.

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ISSCA Announces its 2020 Schedule of Regenerative Medicine Congresses

Wednesday, 15 January 2020 by Benito Novas

The group will host six events across the globe, combining networking and education for practitioners of regenerative medicine

MIAMI LAKES, Florida— The International Society for Stem Cell Application (ISSCA), a worldwide leader in regenerative medicine education, has announced its slate of 2020 medical congresses. The group’s calendar includes dates at six locations across the globe 

Through its congresses, the ISSCA seeks to create a platform through which physicians can collaborate, share data, initiate discussions, and exchange information that may be directly translated to therapeutic applications. All doctors who want to share their medical research are welcome to attend, and the ISSCA welcomes abstract submissions and reviews them on a continuing basis. 

For the second year straight, the main topic discussed at ISSCA’s congresses will be how cellular products derived from birth tissue (allogeneic compounds) have revolutionized the industry by delivering safer, shorter stem cells procedures for practitioners. During each event, lecturers will respond to concerns attendees have about how regenerative medicine advances will satisfy FDA regulations and how new technologies could continue to help patients under new FDA laws.

This year, the ISSCA welcomes three new cities to its agenda—Salvador de Bahia, Brazil; Punta del Este, Uruguay; and Jakarta, Indonesia. The six congresses are as follows: 

  • May 2020: Mexico City, Mexico
  • June 2020: Caracas, Venezuela
  • August 2020: Salvador de Bahia, Brazil
  • October 2020: Buenos Aires, Argentina
  • November 2020: Jakarta, Indonesia
  • December 2020: Punta del Este, Uruguay

“We at the ISSCA are looking forward to this year’s calendar of congresses, which will provide invaluable networking and educational opportunities to physicians looking to expand their knowledge on current innovations and best practices concerning regenerative medicine,” noted Benito Novas, ISSCA VP of Public Relations. “Our global congresses expand on ISSCA’s mission to continue to serve as the premier educational resource for physicians across the globe looking to introduce stem cells treatments into their practices.”

To learn more about the ISSCA or to register for an upcoming congress, visit www.issca.us.

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Global Stem Cells Group Releases New Product to Meet Growing Demand for Birth Tissue Derived Compounds

Wednesday, 15 January 2020 by Benito Novas

Cellgenic Flow Exosomes has a wide range of therapeutic implications, including hair loss and pain management

MIAMI LAKES, Florida—The Global Stem Cells Group (GSCG) has announced the release of a new product in response to growing demands from regenerative medicine practitioners for cellular products derived from birth tissue. The product, Cellgenic Flow Exosomes, is 100% natural and is available in a 1 mL vial comprised of 5 billion exosomes per mL and is currently manufactured in Mexico and in Global’s US-based facilities.

As the popularity and efficacy of stem cells treatments increase across the globe, the demand for cellular products like Cellgenic have also increased. With this demand in mind, the GSCG–a global leader in stem cell research, patient application, and physician training–sought to create an innovative cellular product to meet the needs of physicians looking to offer regenerative medicine treatments in their existing practices.

Cellgenic is primarily comprised of exosomes, cell-derived non-particles that play a pivotal role in cell-to-cell communication that are involved in a wide range of physiological processes. Exosomes play an important role in the transfer of proteins, mRNA, miRNA, and other bioactive molecules between cells and regulate gene expression in recipient cells, thus influencing various molecular pathways.

An increasing amount of attention has been paid to exosomes in recent years thanks to the wide range of therapeutic implications they may hold. Some of the most effective uses for exosomes have come in hair therapy and pain management.

Using Cellgenic as a treatment for hair loss has resulted in prominent hair growth results in both men and women. It is highly recommended for those who are too young for hair transplant surgery and for those within the earlier stages of the hair loss cycle.

In terms of pain management, Cellgenic has shown promise in delivering relief from pain and discomfort and may potentially stimulate repair as opposed to blocking or masking them. Common pain and degenerative conditions that Cellgenic may help treat include osteoarthritis, knee pain, shoulder pain, nerve pain, tendonitis, and slow- and non-healing wounds and burns.

For doctors who are interested in learning more about Cellgenic, the GSCG has developed an online course to provide them with the relevant knowledge needed to make a decision about incorporating allogeneic compounds into their treatment protocols.

“Global’s newest product innovation, Cellgenic Flow Exosomes, is an exciting addition to our product portfolio,” said Benito Novas, CEO of the Global Stem Cells Group. “Our goal is to continually innovate and meet the demands of physicians practicing regenerative medicine by providing cutting-edge therapies for those suffering from degenerative diseases. The release of our Cellgenic product accomplishes this goal while also contributing to our mission of being a leader in stem cells research.”

To learn more about Cellgenic Flow Exosomes, visit https://cellgenic.com/.

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Knee replacement alternatives

Thursday, 26 December 2019 by Benito Novas

One of the amputating surgeries in the field of medicine is a knee replacement. It involves removing the knee joint and replacing it with a modified prosthesis. However, several modifications of this surgery have been introduced into the high-powered world of surgery, including several alternatives for knee replacement. In this article, we are going to review the several modifications and knee replacement alternatives therein. 

What is Knee Replacement?

Knee replacement, also known as knee arthroplasty, is a surgical procedure that involves the amputation or cutting out of a knee joint, the bones reams by a doctor, especially due to accidents or joint ailments such as arthritis. When the bone is removed, it is then replaced with a prosthetic device. Knee replacement can be partial, where selected or affected parts of the joints can be removed, such as the medial, lateral, and anterior compartments can also be removed and replaced with a modified prosthetic.

Why Should You Be looking for a Knee Replacement Alternatives?

Due to the dynamics of the human body, what works for the goose may not necessarily work for the gander. Certain post-symptoms of a knee replacement can be unbearable for most patients.

Pain After Knee Replacement.

Due to pain in the knee joint, a lot of patients embark on this old-time surgery to help reduce the pain they feel around their knee. But it is worthy of knowing that a substantial number of these patients still continue to feel pain after this audacious surgery. In a survey done by the government, 40% of patients that underwent knee replacement experienced miniature pain for over 3-4 years, while another 44% still felt some 3-5/10 degree of pain in 3-4 years. So, it is not worthy of looking in the direction of knee replacement alternatives in order to solve knee pain. 

Knee Replacement Risks.

There is a risk in everything that we do, business, taking a walk, climbing a hill. Same way, certain risks exist in knee replacement which are:

  • Patients become more susceptible to heart attack and stroke immediately after knee replacement surgery. 
  • Increased levels of metals in the blood.
  • Allergic reactions to the prosthetic material.
  • Possibility of infection.
  • Reduced activity of the patient as they thrive to become accustomed to the new prosthesis.

Even though social media and digital marketers paint a vivid picture of beautiful seniors riding a bike, continuing in their daily activities and hobbies, but this may not be true for everyone; in a study conducted by the government, there was seldom activity by patients after knee replacement surgery. Another study showed that patients who weren’t running before a knee replacement surgery couldn’t run after the surgery. But there are always two ways to everything; some other patients also showed an increase in physical activity after their surgery. 

What are Knee Replacement Alternatives?

Steroid Injections

Steroids are made up of corticosteroids and cortisone. These corticosteroids carry out an anti-inflammatory function to prevent swelling around the knee regions as well as help reduce pain. But they do have a side effect; they destroy cartilage and may not be efficient as they are thought to be. If you are considering this knee replacement alternative, you probably should bear in mind that they do not offer long term remedies. Steroid injections are viable for knee replacement needs caused by arthritis but may proffer short-termed solutions. 

Viscosupplementation

Viscosupplementation is also another knee replacement alternative. They are in the form of gels for the knee, also knowns as hyaluronic acid varying across different brands in the market, likes of SynVisc, OrthoVisc, Supartz, and Euflexxa. They are administered to the patient, but a quick question one would ask is if really the shots help. The variations of results all over the web show support both sides of the notion. But one peculiarity of these results is that none says that they are hurtful or damaging as the steroid injections rather that they give a better solution to knee joint arthritis patients. In my own experience, these injections are efficient only when administered a few times, after which they begin to diminish in effects. The first dose may offer relief for some time, but a dose a far-reaching as the sixth dose may not offer any remedial effect at all. 

Knee Nerve Ablation

Knee Nerve ablation is another breakthrough in the surgical world. Knee Nerve Ablation involves the use of technology to carry out a process where the specialist probes the nerves around the joint and passes electrical energy that is used to ablate (destroy) them. The work of these nerves is to relay signals from that region of the knee to the brain. So this technique deadens these nerves, and as such, you don’t feel any pain till those nerves grow back. The research on this type of knee replacement alternative is only a handful. Hence, they cannot conclude on the long term results since most of the studies on this new breakthrough are in their early stages. 

Orthobiologics

Orthobiologics incorporation around the knee regions helps to enhance the healing of the knew joint or reduce the consequent degradation of orthopedic tissues. Orthobiologics are also knee replacement alternatives and can be gotten from the patient as autologous or a donor as allogeneic. The two primary derivations of orthobiologics are the PRP and the BMC short for Bone Marrow Concentrate. Another derivation that is commonly used is derived from natal tissues as in amniotic or umbilical cord. Just as the nerve ablation, the research on this type of knee replacement is at its early stages.

Platelet Rich Plasma (PRP)

We mentioned PRP earlier while discussing orthobiologics. PRP’s stand for Platelet-rich plasma that can be gotten from the patient. They contain healing factors that allow them to foster cartilage repair as well as reduce inflammation and balance the chemical dynamics of the knee. A lot of studies support the efficiency of PRP as knee replacement alternatives but may not offer much help when the arthritis is severe. 

PKA (Percutaneous Knee Arthroplasty)

PKA (Percutaneous Knee Arthroplasty) comes in handy for severe cases of arthritic pain. This procedure involves the injection of rich bone marrow concentrates gotten from the patient or from a donor into the lax ligaments or other affected areas such as damaged meniscus tissues and tendons. This procedure is intricate and uses an ultrasound and fluoroscopy guides as compared to other quick knee shot techniques. Research proves that this method works pretty well, even in extreme cases of knee arthritis. This procedure also produces a lasting effect for about 2-7 years before the need for repetition. 

Here you go!! Knee replacement alternatives. You sure would want to consider some of the alternatives; likes of PKA, PRP, and Bone Marrow concentrates that proffers a long-lasting solution.

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ISSCA Offers New Online Cellular Therapy Course

Thursday, 26 December 2019 by Benito Novas

With video lectures and additional tools from some of the most respected names in today’s stem cells field, the course arms practitioners with the necessary knowledge and resources to offer innovative regenerative medicine treatments in their existing practices

MIAMI LAKES, Florida— The International Society for Stem Cell Application (ISSCA) (www.issca.us) has announced it has launched a new online stem cells course, Cellular Therapy. The course adds to the group’s already existing robust offering of onsite and online courses designed to give physicians looking to incorporate regenerative medicine protocols into their practices the education and tools necessary to do so.

Regenerative medicine has been increasingly gaining attention in today’s fast-paced medical world. As more researchers and physicians become interested in studying the field and introducing treatment protocols into their practices, it can be difficult to know which products and practices yield the best results for patients seeking these treatments for relief from degenerative diseases, noted Benito Novas, ISSCA VP of Public Relations. Knowing which products work for which conditions and how to safely administer them to maximize results are key in leading a successful regenerative medicine practice.

With the Cellular Therapy course and others offered by the ISSCA, physicians will learn these valuable protocols and more about product offerings and how to choose the most effective ones. The Cellular Therapy course will prepare physicians with the necessary theoretical and practical knowledge needed to effectively and safely secure better patient outcomes when using cellular therapies. With this training, physicians will gain knowledge from leading scientists in the field, learn valuable information on safety standards and quality control from top manufacturers, be positioned to perform these procedures and open a Stem Cell Center practice, join the ISSCA’s network, and enjoy the benefits of an exponentially growing industry worldwide.

Practitioners enrolling in the online course will gain access to online lectures from some of the leading names in the field of regenerative medicine spanning a number of topics critical to understanding the foundations of cellular therapy. In addition to online lectures, enrollees gain access to important supporting documents; The Condition Book, outlining stem cells treatment protocols for seven common conditions; and valuable case studies, all designed to deliver the knowledge needed to successfully implement stem cells treatments in a clinical setting.

And physicians looking to enroll in this course and other offerings by the ISSCA are in good hands. The group is widely considered as the global standard bearer when it comes to education and research in the regenerative medicine field. For years, the ISSCA has played a critical role in bridging the gap between the science behind stem cells and regenerative medicine and the practical application of that science in a clinical setting.

“We are pleased to add the online Cellular Therapy course to our growing number of course offerings designed to deliver the skills and education needed to practitioners eager to implement stem cells treatment protocols into their existing practices,” said Novas. “The course gives physicians the skills needed to utilize these highly effective treatments to help patients suffering from degenerative diseases while expanding on the ISSCA’s mission to continue to serve as the premier educational resource for physicians across the globe looking to introduce stem cells treatments into their practices.”

To learn more about the ISSCA, visit www.issca.us. To learn more about the group’s new online Cellular Therapy course or to register, visit https://www.cellulartherapycourse.com/

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Conventional and novel stem cell based therapies for androgenic alopecia

Tuesday, 17 December 2019 by Benito Novas

Dodanim Talavera-Adame,1 Daniella Newman,2 Nathan Newman1

1American Advanced Medical Corp. (Private Practice), Beverly Hills, CA, 

2Western University of Health Sciences, Pomona, CA, USA

Abstract

The prevalence of androgenic alopecia (AGA) increases with age and it affects both men and women. Patients diagnosed with AGA may experience decreased quality of life, depression, and feel self-conscious. There are a variety of therapeutic options ranging from prescription drugs to non-prescription medications. Currently, AGA involves an annual global market revenue of US$4 billion and a growth rate of 1.8%, indicating a growing consumer market. Although natural and synthetic ingredients can promote hair growth and, therefore, be useful to treat AGA, some of them have important adverse effects and unknown mechanisms of action that limit their use and benefits. Biologic factors that include signaling from stem cells, dermal papilla cells, and platelet-rich plasma are some of the current therapeutic agents being studied for hair restoration with milder side effects. However, most of the mechanisms exerted by these factors in hair restoration are still being researched. In this review, we analyze the therapeutic agents that have been used for AGA and emphasize the potential of new therapies based on advances in stem cell technologies and regenerative medicine. 

Introduction

The prevalence of androgenic alopecia (AGA) increases with age, and is estimated to affect about 80% of Caucasian men.1 Female AGA, also known as female pattern hair loss, affects 32% of women in the ninth decade of life.2 The consumer market for products that promote hair growth has been increasing dramatically.3 These products promote hair regeneration based on the knowledge about the hair follicle (HF) cycle.4,5 However, in most cases, the mechanisms of action of these products are not well characterized and the results are variable or with undesirable side effects.6 At present, only two treatments for AGA have been approved by the US Food and Drug Administration (FDA): Minoxidil and Finasteride.7–10Although these medications have proved to be effective in some cases, their use is limited by their side effects.11,12 With the emergence of stem cells (SCs), many mechanisms that lead to tissue regeneration have been discovered.13 Hair regeneration has become one of the targets for SC technologies to restore the hair in AGA.14 Several SC factors such as peptides exert essential signals to promote hair regrowth.15,16 Some of these signals stimulate differentiation of SCs to keratinocytes which are important for HF growth.17 Other signals can stimulate dermal papilla cells (DPCs) that promote SC proliferation in the HF.18,19 In this review, we describe HF characteristics and discuss different therapies used currently for AGA and possible novel agents for hair regeneration. These therapies include FDA-approved medications, non-prescription physical or chemical agents, natural ingredients, small molecules, biologic factors, and signals derived from SCs.

HF and SC niche

The HF undergoes biologic changes from an actively growing stage (anagen) to a quiescent stage (telogen) with an intermediate remodeling stage (catagen).4 HFSCs are located in the bulge region of the follicle and they interact with mesenchymal SCs (MSCs) located in the dermal papilla (DP).18 These signal exchanges promote activation of some cellular pathways that are essential for DPC growth, function, and survival, such as the activation of Wnt signaling pathway.19–21 Other signals, such as those from endothelial cells (ECs) located at the DP, are also essential for HF maintenance.22 EC dysfunction that impairs adequate blood supply may limits or inhibits hair growth.22 For instance, Minoxidil, a synthetic agent, is able to promote hair growth by increasing blood flow and the production of prostaglandin E2 (PGE2).7 It has been shown that proteins that belong to the transforming growth factor (TGF) superfamily, such as bone morphogenetic proteins (BMPs), also exert signals to maintain the capacity of DPCs to induce HF growing in vivo and in vitro.23 These BMPs may be released by several cells that compose the follicle, including ECs.24–26 ECs may provide signals for BMP receptor activation in DPCs similar to those signals that promote survival of MSCs in human embryoid bodies composed of multipotent cells.24,25 DPCs have been derived from pluripotent SCs in an attempt to study their potential for hair regeneration in vitro and in vivo.27 Together, dermal blood vessels and DPCs orchestrate a suitable microenvironment for the growth and survival of HFSCs.28,29 Interestingly, the expression of Forkhead box C1 regulates the quiescence of HFSCs located in the bulge region (Figure 1).30 HFSCs are quiescent during mid-anagen and maintain this stage until the next hair cycle.29,30 However, during early anagen stage, these cells undergo a short proliferative phase in which they self-renew and produce new hair.30 Therefore, the bulge region constitutes a SC niche that makes multiple signals toward quiescence or proliferation stages.30–34 It is known that fibroblasts and adipocyte signals are able to inhibit the proliferation of HFSCs.34 Additionally, BMP6 and fibroblast growth factor 18 (FGF18) from bulge cells exert inhibitory effects on HFSC proliferation.34 Dihydrotestosterone (DHT) also inhibits HF growth.35 Agents that reduce DHT, such as Finasteride, promote hair regrowth by inhibiting Type II 5a-reductase.8,14,36 In contrast to these inhibitory effects, DPCs located at the base of the HF provide activation signals (Figure 1).18,34 The crosstalk between DPCs and HFSCs leads to inhibition of inhibitory effects with the resultant cell proliferation toward hair regeneration (anagen).30,31,37 With the self-renewal of HFSCs, the outer root sheath (ORS) forms, and signals from DPCs to the bulge cells diminish in a way that the bulge cells start again with their quiescent stage.4,34As mentioned earlier, Forkhead box C1 transcription factor has an important role in maintaining the threshold for HFSC activation.30 The knockdown of these factors in bulge cells reduces the cells’ threshold for proliferation, and the anagen cycle starts more frequently due to promotion of HFSC proliferation in shorter periods of time.30

Figure 1 Diagram of the HF and factors involved in hair regeneration.

Notes: The HF is composed of different cell types including HFSCs, DPCs, and ECs, among others. HFSCs migrate from the bulge area after activation by growth factors released by DPCs. However, BMP6 and FGF18 from the bulge cells exert autocrine inhibitory effects in HFSC proliferation. Once the HFSCs are closer to DPCs and ECs, they differentiate and proliferate during anagen phase, forming new hair. Activation of Wnt signaling is essential for DPCs to release the factors that promote differentiation and proliferation of HFSCs. DHT interferes with this Wnt signaling and, in this way, inhibits hair growth and promotes hair miniaturization. Effective cell–cell interactions between HFSCs, DPCs, and ECs are essential for hair growth.

Abbreviations: BMP6, bone morphogenetic protein 6; DHT, dihydrotestosterone; DP, dermal papilla; DPCs, dermal papilla cells; ECs, endothelial cells; FGF18, fibroblast growth factor 18; HF, hair follicle; HFSCs, hair follicle stem cells.

Prescribed and non-prescription products that promote hair growth and possible mechanisms of action

FDA-approved chemical agents

At present, the only therapeutic agents for AGA approved by the FDA in the USA are Finasteride and Minoxidil.9,10 Minoxidil promotes hair growth by increasing the blood flow and by PGE2 production.7Although Minoxidil is now a non-prescription medication, Finasteride and other drugs require a medical prescription for AGA treatment (Table 1). Dutasteride and Finasteride inhibit 5a-reductase, blocking the conversion of testosterone to DHT.36,38 While Finasteride is a selective inhibitor of type II 5a-reductase, Dutasteride inhibits type I and type II 5a-reductases. These medications have also been used to treat benign prostatic hyperplasia.39

Table 1

Prescribed products used for AGA

Prescribed products Source Mechanism of action
Finasteride/Dutasteride9,10 Synthetic (small molecule) Inhibits type II, 5a-reductase
Latanoprost and Bimatoprost36,38,39,79,80 Synthetic prostaglandin analog of PGF2a (originally used to decrease ocular pressure in glaucoma) Activates prostaglandin receptor

Abbreviation: AGA, androgenic alopecia; PGF2a, prostaglandin F2a.

Natural ingredients

In addition to prescribed medications, some natural ingredients have been used to promote hair growth (Table 2). For example, procyanidin B-2 (found in apples and in several plants) is able to inhibit the translocation of protein kinase C (PKC) in hair epithelial cells.40 PKC isozymes, such as PKC-ßI and -ßII, play an important role in hair cycle progression and inhibiting their translocation can promote hair growth.40 Procyanidin B-3 can promote hair growth by inhibiting TGF-ß1.41 Another group of natural ingredients, such as saw palmetto, alfatradiol, and green tea (Epigallocatechin gallate), have the capacity to inhibit 5a-reductase and block DHT production.42–44 The natural ingredients and their proposed mechanisms of action are summarized in Table 2 (the commercial web page is included, since there are no formal studies about their mechanisms of action).

Table 2

Non-prescription products used for AGA and their proposed mechanisms of action

Non-prescription product Source Proposed mechanism of action
Minoxidyl (FDA approved)9 Synthetic (small molecule) Potassium channel opener and powerful vasodilator used in hypertension
Apple Procyanidin B-2 (extract from apples)40 Natural (apples and several plants) Inhibitor of translocation of PKC isozymes in hair epithelial cells
Procerin (saw palmetto extract and other ingredients such as iodine, gotu kola, magnesium, grape seed extract, biotin, niacin, and vitamin B12)42 Natural (small plant named saw palmetto) Used to treat benign prostatic hyperplasia.
Inhibits type I and II 5a-reductase and blocks DHT production
Provillus (www.provillus.com) Formulation (Minoxidil 2 or 5%, biotin, Zn, Fe, Mg, Ca, B6 complex) Contains Minoxidil and more vitamins (similar ingredients to Procerin)
Follicusan (https://www.ulprospector .com/ en/na/PersonalCare/Detail /1381/216299/Follicusan-DP) Natural (milk-based bioactive compound) Stimulates cellular functioning in the scalp and hair follicle. Stimulates dermal papilla cells.
Improve hair density and thickness
Musol 20 (http://www.cosmeticingredients.co.uk /Ingredient/musol-20-pf) Natural (yeast extract, mucoprotein) Physically deposited as a protective covering to create thicker hair
Capixyl (http://lucasmeyercosmetics.com /en/products/product.php?id=6) Synthetic and natural (four amino acids biomimetic peptide with red clover extract; rich in biochanin A [antioxidant]) Inhibitor of 5a-reductase, improves ECM proteins; it reduces inflammation
EMortal Pep (http://www.revagain.co.kr /goods/catalog?code=0002) Synthetic and natural Blocks upregulation of TGF-ß1 induced by DHT.
Activates dermal papilla cells
Planoxia-RG (https://www.ulprospector.com /en/na/PersonalCare/Detail/ 5314/195870/PLANOXIA-RG) Natural Promotes transition from telogen phase to anagen phase
Tricholastyl (http://dir.cosmeticsandtoiletries.com /detail/tradeName.html?id=17820) Natural (water, mannitol, Pterocarpus marsupium bark extract, disodium succinate, glutamic acid) Antiglycation activity. In this way, it restores the hair growth cycle
Keramino-25 (http://www.lonza.com /productsservices/consumercare /personalcare/proteins/animal-proteins /keramino-25.aspx) Synthetic Increases the strength of the hair (because of its great penetration)
Seveov (http://www.naturex.asia /uk_1/markets/personal-care/natbeautytm/seveov.html) Natural (maca root extract) It protects the hair bulb and shaft. It stimulates cell division in the hair shaft and bulb
Hairomega (http://thehairlossreview.com /hairomega_review.html/) Natural (formulation that contains [200 mg] saw palmetto and [300 mg] ß-sitosterol as the main ingredients) Inhibits 5a-reductase and formation of DHT
Green tea (Epigallocatechin gallate)43,91 Natural (polyphenol antioxidant) Inhibits 5a-reductase and formation of DHT
Nioxin (formulation of Coenzyme Q10 and other coenzymes) http://www.nioxin.com /en-US?&utm_source=google& utm_medium=cpc &utm_term=nioxin &utm_campaign= Nioxin_Search_Brand +Awareness& utm_content =sMPLlfxxa| dc_45273195217_e_nioxin& gclid=CJSy3JbH0cgCFY17fgodMTIDK Q Synthetic Inhibits 5a-reductase and formation of DHT
Alfatradiol (17a-estradiol)44 Synthetic (small molecule) Inhibits type II 5a-reductase
Quercetin84 Natural (flavonoid found in several non-citrus fruits, vegetables, leaves, and grains) Inhibits PGD2
 
Abbreviations: AGA, androgenic alopecia; DHT, dihydrotestosterone; ECM, extracellular matrix; FDA, US Food and Drug Administration; PGD2, prostaglandin D2; PKC, protein kinase C; TGF-ß1, transforming growth factor ß1.

Laser therapy

Light amplification by stimulated emission of radiation (LASER) generates electromagnetic radiation which is uniform in polarization, phase, and wavelength.45 Low-level laser therapy (LLLT), also called “cold laser” therapy, since it utilizes lower power densities than those needed to produce heating of tissue. Transdermal LLLT has been used for therapeutic purposes via photobiomodulation.46,47 Several clinical conditions, such as rheumatoid arthritis, mucositis, pain, and other inflammatory diseases, have been treated with these laser devices.48–50 LLLT promotes cell proliferation by stimulating cellular production of adenosine triphosphate and creating a shift in overall cell redox potential toward greater intracellular oxidation.51 The redox state of the cell regulates activation of signaling pathways that ultimately promotes high transcription factor activity and gene expression of factors associated with the cell cycle.52 Physical agents such as lasers have been also used to prevent hair loss in a wavelength range in the red and near infrared (600–1,070 nm).5,47,51,53 Laser therapy emits light that penetrates the scalp and promotes hair growth by increasing the blood flow.54 This increase gives rise to EC proliferation and migration due to upregulation of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase.55,56 In addition, the laser energy itself stimulates metabolism in catagen or telogen follicles, resulting in the production of anagen hair.53,54A specific effect of LLLT has been demonstrated to promote proliferation of HFSCs, forcing the hair to start the anagen phase.57

Biologic agents that promote hair growth and their mechanisms of action

SC signaling

Recently, it has been found that SCs release factors that can promote hair growth.16 These factors and their mechanisms of action have been summarized in Table 3. These factors, known as “secretomes”, are able to promote skin regeneration, wound healing, and immunologic modulation, among other effects.58,59 Some of these factors, such as epidermal growth factor (EGF), basic fibroblast growth factor, hepatocyte growth factor (HGF) and HGF activator, VEGF, insulin-like growth factor (IGF), TGF-ß, and platelet-derived growth factor (PDGF), are able to provide signals that promote hair growth.15,60–64 As mentioned before, DPCs provide signals to HFSCs located in the bulge that proliferate and migrate either to the DP or to the epidermis to repopulate the basal layer (Figure 1).32,65 Enhancement in growth factor expression (except for EGF) has been reported when the adipose SCs are cultured in hypoxic conditions.15 Also, SCs increase their self-renewal capacity under these conditions.66–68 Low oxygen concentrations (1%–5%) increase the level of expression of SC factors that include VEGF, basic fibroblast growth factor, IGF binding protein 1 (IGFBP-1), IGF binding protein 2 (IGFBP-2), macrophage colony-stimulating factor (M-CSF), M-CSF receptor (M-CSFR), and PDGF receptor ß (PDGFR-ß).15,69,70 While these groups of factors promote HF growth in intact skin, another group of factors, such as M-CSF, M-CSFR, and interleukin-6, are involved in wound-induced hair neogenesis.71 HGF and HGF activator stimulate DPCs to promote proliferation of epithelial follicular cells.61 Epidermal growth factor promotes cellular migration via the activation of Wnt/ß-catenin signaling.60 VEGF promotes hair growth and increases the follicle size mainly by perifollicular angiogenesis.72 Blocking VEGF activity by neutralizing antibodies reduced the size and growth of the HF.72 PDGF and its receptor (PDGFR-a) are essential for follicular development by promoting upregulation of genes involved in HF differentiation and regulating the anagen phase in HFs.64,73 They are also expressed in neonatal skin cells that surround the HF.73 Monoclonal antibodies to PDGFR-a (APA5) produced failure in hair germ induction, supporting that PDGFR-a and its ligand have an essential role in hair differentiation and development.73 IGF-1 promotes proliferation, survival, and migration of HF cells.69,74 In addition, IGF binding proteins (IGFBPs) also promote hair growth and hair cell survival by regulating IGF-1 effects and its interaction with extracellular matrix proteins in the HF.70 Higher levels of IGF-1 and IGFBPs in beard DPCs suggest that IGF-1 levels are associated with androgens.74 Furthermore, DPCs from non-balding scalps showed significantly higher levels of IGF-1 and IGFBP-6, in contrast to DPCs from balding scalps.74

Table 3 

Stem cell factors and small molecules that promote hair growth and their mechanisms of action

Factor Mechanism of action
HGF and HGF activator61 Factor secreted by DPC that promotes proliferation of epithelial follicular cells
EGF60 Promotes growth and migration of follicle ORS cells by activation of Wnt/ß-catenin signaling
bFGF62 Promotes the development of hair follicle
IL-693 Involved in WIHN through STAT3 activation
VEGF72 Promotes perifollicular angiogenesis
TGF-ß63 Stimulates the signaling pathways that regulate hair cycle
IGF-169 Promotes proliferation, survival, and migration of hair follicle cells
IGFBP-1 to -670 Regulates IGF-1 effects and its interaction with extracellular matrix proteins at the hair follicle level
BMP23 Maintains DPC phenotype which is crucial for stimulation of hair follicle stem cell
BMPR1a23 Maintains the proper identity of DPCs that is essential for specific DPC function
M-CSF71 Involved in wound-induced hair regrowth
M-CSFR71 Involved in wound-induced hair regrowth
PDGF and PDGFR-ß/-a64 Upregulates the genes involved in hair follicle differentiation. Induction and regulation of anagen phase. PDGF and its receptors are essential for follicular development
Wnt3a97 Involved in hair follicle development through ß-catenin signaling
PGE279,80 Stimulates anagen phase in hair follicles
PGF2a and analogs79,80 Promotes transition from telogen to anagen phase of the hair cycle
BIO98 GSK-3 inhibitor
PGE2 or inhibition of PGD2 or PGD2 receptor D2/GPR4477 Promotes follicle regeneration
Iron and l-lysine95 Under investigation

Abbreviations: bFGF, basic fibroblast growth factor; BIO, (2’Z,3’E)-6-bromoindirubin-3′-oxime; BMP, bone morphogenetic protein; DPCs, dermal papilla cells; EGF, epidermal growth factor; GSK-3, glycogen synthase kinase-3; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor 1; IGFBP-1, insulin-like growth factor-binding protein 1; IL-6, interleukin-6; M-CSF, microphage colony-stimulating factor; M-CSFR, microphage colony-stimulating factor receptor; ORS, outer root sheath; PDGF, platelet-derived growth factor; PDGFR-a, platelet-derived growth factor receptor alpha; PDGFR-ß, platelet-derived growth factor receptor beta; PGD2, prostaglandin D2; PGE2, prostaglandin E2; TGF-ß1, transforming growth factor ß1; VEGF, vascular endothelial growth factor; WIHN, wound-induced hair neogenesis; Wnt3a, wingless-type MMTV integration site family, member 3A.

Small molecules

Small molecules with low molecular weight (<900 Da) and the size of 10-9 m are organic compounds that are able to regulate some biologic processes.75 Some small molecules have been tested for their role in hair growth.76 Synthetic, non-peptidyl small molecules that act as agonists of the hedgehog pathway have the ability to promote follicular cycling in adult mouse skin.76 PGE2 and prostaglandin D2 (PGD2) have also been associated with the hair cycle (Table 3).77 PGD2 is elevated in the scalp of balding men and inhibits hair lengthening via GPR44 receptor.78 Also, it is known that PGE2 and PGF2a promote hair growth, while PGD2 inhibits this process.77,79 Prostaglandin analogs of PGF2a have been used originally to decrease ocular pressure in glaucoma with parallel effects in the growth of eyelashes, which suggests a specific effect in HF activation.80 PGD2 receptors are located in the upper and lower ORS region and in the DP, suggesting that these prostaglandins play an important role in hair cycle.81 Molecules such as quercetin are able to inhibit PGD2 and, in this way, promote hair growth.82–84 Antagonists of PGD2 receptor (formally named chemoattractant receptor-homologous expressed in Th2 cells) such as setipiprant have been used to treat allergic diseases such as asthma, but they also have beneficial effects in AGA.85–87 Another small molecule l-ascorbic acid 2-phosphate promotes proliferation of ORS keratinocytes through the secretion of IGF-1 from DPCs via phosphatidylinositol 3-kinase.88 Recently, it has been described that small-molecule inhibitors of Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway promote hair regrowth in humans.89 Janus kinase inhibitors are currently approved by the FDA for the treatment of some specific diseases such as psoriasis and other autoimmune-mediated diseases.90–94 Also, another group of small molecules such as iron and the amino acid l-Lysine are essential for hair growth (Table 3).95

Cellular therapy

The multipotent SCs in the bulge region of the HF receive signals from DPCs in order to proliferate and survive.27,28,65,84,96 It has been shown that Wnt/ß-catenin signaling is essential for the growth and maintenance of DPCs.19,97 These cells can be isolated and cultured in vitro with media supplemented with 10% fetal bovine serum and FGF-2.37,98 However, they lose versican expression that correlates with decrease in follicle-inducing activity in culture.98 Versican is the most abundant component of HF extracellular matrix.99 Inhibition of glycogen synthase kinase-3 by (2’Z,3’E)-6-bromoindirubin-3′-oxime (BIO) promotes hair growth in mouse vibrissa follicles in culture by activation of Wnt signaling.98 Therefore, the increase of Wnt signaling in DPCs apparently is one of the main factors that promote hair growth.19 DPCs have been also generated from human embryonic SCs that induced HF formation after murine transplantation.27

Platelet-rich plasma

Platelets are anucleate cells generated by fragmentation of megakaryocytes in the bone marrow.100 These cells are actively involved in the hemostatic process after releasing biologically active molecules (cytokines).100–102 Because of the platelets’ higher capacity to produce and release these factors, autologous platelet-rich plasma (PRP) has been used to treat chronic wounds.103 Therefore, PRP can be used as autologous therapy for regenerative purposes, for example, chondrogenic differentiation, wound healing, fat grafting, AGA, alopecia areata, facial scars, and dermal volume augmentation.101,104–108 PRP contains human platelets in a small volume that is five to seven times higher than in normal blood and it has been proven to be beneficial to treat AGA.10,105,109–111 The factors released by these platelets after their activation, such as PDGFs (PDGFaa, PDGFbb, PDGFab), TGF-ß1, TGF-ß2, EGF, VEGF, and FGF, promote proliferation of DPCs and, therefore, may be beneficial for AGA treatment.109,112–114 Clinical experiments indicate that patients with AGA treated with autologous PRP show improved hair count and thickness.109

In search of novel therapies

In this paper, we reviewed and discussed the use of therapeutic agents for hair regeneration and the knowledge to promote the development of new therapies for AGA based on the advances in regenerative medicine. The HF is a complex structure that grows when adequate signaling is provided to the HFSCs. These cells are located in the follicle bulge and receive signals from MSCs located in the dermis that are called DPCs. The secretory phenotype of DPCs is determined by local and circulatory signals or hormones. Recent discoveries have demonstrated that SCs in culture are able to activate DPCs and HFSCs and, in this way, promote hair growth. The study of these cellular signals can provide the necessary knowledge for developing more effective therapeutic agents for the treatment of AGA with minimal side effects. Therefore, advancements in the field of regenerative medicine may generate novel therapeutic alternatives. However, further research and clinical studies are needed to evaluate their efficacy.

Disclosure

The authors report no conflicts of interest in this work.

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