To understand why stem cell platelet-rich plasma or co-transplantation of Adipose-derived mesenchymal stem cells and PRP, is such a remarkable idea in regenerative medicine, let’s spend a little time looking at the mechanics of PRP.
Platelet-Rich Plasma’s Role As Repairmen
The one thing that makes Platelet-Rich Plasma a hero in several fields (if not all) of medicine is the fact that the diverse growth factors in it are able to stimulate stem cell proliferation and cell differentiation (the factors that determine effective tissue regeneration and healing) on any part of the body.
These growth factors are abundant in the blood and act as the natural repairmen of tissues.
In the perfect scenario, there’s plenty of blood flow to every part of the body and these “repairmen” are always on-call to address any healing needs that may arise. However, if the injured area has a poor blood supply — especially areas that are constantly move like tendons, ligaments and joints — demand for these repairmen can outgrow supply. Meaning, healing (or regeneration of tissues) is put on hold till further repairmen are available.
The train of Platelet-Rich Plasma then arrives with enough of these repairmen to warrant resumption of healing.
There’s another part of this picture we haven’t talked about so far: stem cells.
As far as Platelet-Rich Plasma and it’s growth factors are concerned, they are mere repairmen. They can’t do the work by themselves. They need the basic raw materials to work with. And that raw material here is the stem cells.
Stem cells are the ones actually being regenerated to form new tissues for healing.
Stem Cells As The Raw Materials For PRP
Stem cells are the only raw materials that PRP works with for regeneration. These are like the fundamental building blocks of all other cells. These cells can be can be guided into becoming specialized cells under the right conditions.
In addition, they can also divide themselves to form new stem cells or new specialized cells.
So for Platelet-Rich Plasma to work well, it needs to be applied to an area with lots of stem cells like the heart, liver, blood vessels etc. Incidentally Platelet-Rich Plasma’s healing properties were first discovered by cardiac surgeons who played with concentrated blood for faster healing of heart after surgery and it showed tremendous promise because stem cells are abundant in heart tissues.
But what if healing is needed in an area where there are not much stem cells?
With the new developments in stem cell technology that can be solved too. Because now we can supply the stem cells to areas where there are less like the joints, ligaments and tendons. For this, scientists usually use “mesenchymal stem cell” or MSCs. These are cells isolated from stroma and can differentiate to form adipocytes, cartilage, bone, tendons, muscle, and skin.
The most easiest way is to harvest it from adipose tissue or fat that we call Adipose-derived mesenchymal stem cells or ADSC.
Stem Cell Platelet-Rich Plasma
Supplying Both PRP And Stem Cells For Regeneration
In regions with hypoxia (poor blood supply) like joints, meniscus tissue, rotator cuff, spinal discs etc the supply of platelets (and therefore growth factors) as well as the stem cells are limited. So what if we supplied both the stem cells and Platelet-Rich Plasma for triggering the regeneration process?
That’s the question these Japanese scientists answered in their research. Here’s another group of scientists who took on the same challenge.
They used Adipose-derived mesenchymal stem cells (ADSC) which is known for their ease of isolation and extensive differentiation potential. These researchers noted that these stem cells often can’t survive in areas of local hypoxia, oxidative stress and inflammation – thereby making them ineffective. However, when Platelet-Rich Plasma (or thrombin-activated PRP) is added to ADSC, it kept them alive for prolonged periods and the growth factors in the Platelet-Rich Plasma triggered cell differentiation and proliferation more easily.
Why This Exact Combination Is The Future
Done this way, both Adipose-derived mesenchymal stem cells (ADSC) and Platelet-Rich Plasma are raw materials for healing that’s already available in plenty in almost every one (there are exceptions of course). That means, for complete healing to take place this combination treatment, still in it’s very primitive stage of development, may have the potential to replace expensive synthetic drugs that carry complex unexplained side effects. The procedure takes our body’s natural healing agents — stem cells from body fat and PRP from blood — and then inject it inside knee or other joints (or other areas where they are insufficient) for regeneration.
Isn’t that like the most wonderful thing ever?
Whether it’s cartilage cell, or a bone cell, or a collagen cell for ligaments and tendons that needs to be healed, all you need is a same-day procedure by a local, but specialized doctor, using the natural ingredients of the body.
I believe this special combo is a huge win for Platelet-Rich Plasma.
The Challenges For Growing Adoption Of This Treatment
We know Platelet-Rich Plasma has safe, yet high-speed recovery potential with it’s multiple growth factors. And it is effective in regenerative healing of cartilage injuries – the most toughest injuries to heal – as well as Osteoarthritis. However the challenges are Platelet Quality. We need to somehow ensure the Platelet-Rich Plasma quality is uniform. Currently it varies from two to several fold above baseline concentration based on donor’s physical condition.
Next we need to identify the exact PRP growth factors that promote ADSC proliferation. Scientists believe growth factors such as basic fibroblast growth factor (bFGF), epidermal growth factor, and platelet-derived growth factor stimulate stem cell proliferation while some growth factors under certain conditions are known to inhibit the process.
The percentage of PRP matters too. 5 percent, 10 percent, 15 percent and 20 percent Platelet-Rich Plasma in ADSC are tested by scientists.
The Only Treatment In Modern Medicine For Cartilage Regeneration
The bottom line is that Stem Cell Platelet-Rich Plasma or ADSC + PRP procedure is the only treatment in modern medicine that has showed cartilage regeneration. So it’s too important to ignore. And it could one of greatest advances that science has brought to the millions of people suffering from serious pain in their joints, knee and spine as well people suffering from all kinds of tendon diseases and injuries.
Since it is a new science, many people are skeptical about Platelet-Rich Plasma, otherwise known as PRP. There are some studies out there that state that PRP work no better than a similarly administered placebo, but there are many other studies and doctors that claim that PRP works and works well. This also works well at a much lower cost and less side effects, than traditional medicine.
One branch where the skepticism is loud and clear is podiatry, which deals with feet and ankles. Trying to combat this skepticism can help many surgeons to lower complication rates, improve patient satisfaction, and have better outcomes. For instance, here is a list of cases where PRP has been effective for the feet and ankles.
- Plantar Fasciitis
PRP has become rather common as a treatment for Plantar Fasciitis, with many studies to prove the efficacy of this treatment. For instance, Dr. Daanial Kassicieh or Sarasota Neurology claims that PRP is one of the most effective treatments for this condition, and that PRP is actually fully cure it. Many of his patients have avoided surgery just by utilizing PRP therapy.
This is done with no down time, no rehabilitation, and no side effects. This woud explain why plantar fasciitis is the 5th popular medical condition treated by PRP. This can be explained by over 3 million people that are diagnosed with this and no other treatment really works for it, besides, in fact, PRP.
- Archilles Tendonitis
This is another condition that can be fairly hard to treat, and gets worse over time unless healed. Many surgical approaches are often trickey and generally do not end up with good results. Because of this, the main treatment option is simply to give patients corticosteroids to reduce the pain, but really nothing else to treat the symptoms.
However, there have been many studies done that have shown that PRP is a lot more effective, including that from the European Foot and Ankle Society. This means that PRP is safer and more effective alternative than any other treatments available.
- Diabetic Foot Ulcers
Diabetic foot ulcers can be troublesome, especially when they do not heal or heal properly. Over 2.5 million Americans with diabetes who suffer from these ulcers. About 11% of these cases may need amputation of their affected limb. However, some studies have noted that just one injection of PRP and a topical solution bi-weekly started to heal the ulcers in just 8 weeks. Topical PRP also has been shown to work better than anti-septic creams as well.
- Regenerating Bones
Bone regeneration is most commonly needed in food and ankle area. Although mechanical stabilization works best, the utilization of PRP has been surprising. PRP helps with healing bones and soft tissue at the damage site. According to a recent systematic review of 64 articles, the conclusion was to include more PRP therapy into the healing of foot and ankle bones.
The science behind this is solid, for bone or tissue to form, three things are needed in the area:
- A scaffold for the growth to take place
- Biological stimulants to signal proteins
- Stem cells that provide bone building potential
All three of these are crucial for bone formation.. PRP can provide at least two of these, so there is no reason to ignore it when it comes to bone regeneration.
- Ankle Sprains
This is an incredibly common condition, and can be effectively treated by using PRP therapy. In one randomized controlled trial, researchers studied the effects of PRP injections on athletes with ankle sprains. This study showed that not only did PRP reduce the healing time by 20 days, but that they also experienced much less pain. This can reduce the recovery period from 6 weeks, for just about 2 or 3 weeks.
Immobilization is Vital
When it comes to foot and ankle related injuries, one thing that really cannot be avoided in rest and rehabilitation. This is true regardless of whether PRP is administered. Because of this, many of the studies that shows PRP to be ineffective often don’t use rest and rehabilitation, and that alone can be an issue.
PRP is in no way a magic pill. All foot injuries need rest and rehabilitation in order to properly heal. With these two combined, it can drastically reduce healing times.
How can Foot and Ankle Surgeons Benefit?
Using PRP in foot and ankle injuries is not going anywhere, so utilizing it would be the best way to go. Test it out with your patients, and try using platelet-rich plasma therapy instead of simply prescribing pills or doing costly surgeries. Your patients will thank you in the end.
Musculoskeletal tissue injuries and degeneration are common and debilitating for a high number of patients (Brooks, 2006). Unfortunately, endogenous musculoskeletal tissue regeneration is limited in many cases and may be affected by inflammation and the degree of damage. For example, most fractures of long bones heal spontaneously, whereas large segmental defects fail to heal. Additionally, although articular cartilage has almost no intrinsic reparative potential, tendons and ligaments may heal, but often with inferior properties. The high prevalence of these injuries has led to significant investment in the development of new therapies to enhance healing and augment current surgical interventions. Often the goal is to mimic and recapitulate the natural healing cascade and developmental process by transplantation of tissue-specific stromal and progenitor cells or by endogenous manipulation to enhance the native repair capacity of cells.
There has been a continuing increase in the number and type of stem and stromal cells being pursued in human clinical trials for treatment of musculoskeletal injuries (Steinert et al., 2012). Most approaches in this area are based on ex vivo-expanded mesenchymal stromal cells (MSCs) derived from bone marrow (BM). Originally identified and characterized by their multilineage differentiation potential in vitro, multipotent capabilities of MSCs in vivo have not been clearly demonstrated to date, particularly because of the lack of methods to identify and define differentiated populations (Nombela-Arrieta et al., 2011). Central to recent progress in the field has been the understanding that stem and progenitor functions of MSCs may not be the key attribute that mediates tissue repair. In addition, there is outstanding controversy over the terminology of exogenously supplied MSCs as stromal cells, and various terms, including medicinal signaling cells, have been proposed to more accurately reflect their therapeutic function in vivo (Caplan, 2017). Nevertheless, the therapeutic benefit of these cells has been largely explored. Significant advances have been made in developing strategies that deliver, protect, and recruit stem cells, and the bioengineering field is evolving to improve current surgical techniques.
This review first describes current treatments and reports the recent progress in clinical investigations of stem and stromal cell-based therapies for musculoskeletal repair with a particular focus on bone and fibrocartilaginous tissues. The current understanding of appropriate cell sources and delivery strategies is then illustrated toward endogenous repair of musculoskeletal tissues. Last, emerging therapeutic concepts are highlighted in the context of biomaterials as a particularly attractive tool to control stem and stromal cell behavior both ex vivo and in vivo, to recruit endogenous stem cells, and to control the local healing environment. Such approaches have great potential for future therapies in musculoskeletal repair.
The intrinsic repair of bone defects mirrors many events of embryonic development and makes fracture healing one of the rare postnatal processes that are regenerative and can ultimately restore damaged tissue to its pre-injury structure, composition, and biomechanical function (Figure 1). In spite of the unique capacity of bone to heal, a number of clinical indications remain where therapeutic intervention is required. In the case of complex trauma with multiple fractures, infections, and tumor-associated and endocrine diseases (e.g., diabetes, osteoporosis), the body’s natural healing response is impaired, and non-union can occur in up to 15% of cases (Grayson et al., 2015). Another debilitating disorder is non-traumatic avascular osteonecrosis, which can lead to collapse of the femoral head and accounts for 10,000–20,000 total hip replacement surgeries in the United States per year (Figure 1; Moya-Angeler et al., 2015). Autologous bone grafting represents the gold standard for management of bone defects and non-unions, and union rates of more than 90% have been reported using iliac crest bone. However, considerable donor site morbidity and limited volumes must be taken into consideration. Additionally, allogeneic or synthetic bone substitutes, such as ceramics, corals, or polymer-based materials, have not reached the biological and mechanical properties equivalent to autologous bone (Table 1).
In addition to direct traumatic injury, complex damage of bone tissue (e.g., open fractures, tumor ablations) often results in concomitant soft tissue injury, including adjacent muscles. Although skeletal muscle has the inherent ability to regenerate after injuries, the regenerative capacity fails when a large volume of muscle is lost (i.e., volumetric loss). Such severe injuries may lead to fibrosis, atrophy, and ischemia when left untreated, accounting for significant socioeconomic costs ($18.5 billion in healthcare costs are associated with sarcopenia alone) (Janssen et al., 2004). Therapeutic treatment options are limited to physical therapy, scar tissue debridement, and transfer of healthy, innervated, and vascularized autologous muscle tissue. However, the outcomes of surgical reconstructions often remain aesthetically and functionally deficient (Grogan et al., 2011; Table 1).
Articular Cartilage and Meniscus
In contrast to bone and skeletal muscle tissue, the poor intrinsic healing capacity of articular cartilage and meniscus tissue presents a major challenge in clinics. Lesions from injuries or degeneration often result in gradual tissue erosion, leading to impaired function of the affected joint and degenerative osteoarthritis (OA) (Figure 1). Patients with post-traumatic OA account for more than 10% of the 27 million adults in the United States that have a clinical diagnosis of OA (Johnson and Hunter, 2014). Commonly, the first-line treatment of articular injuries includes arthroscopic lavage, partial meniscectomy, and BM stimulation techniques to penetrate subchondral bone (Table 1). Microfracture has been considered the gold standard for stimulating endogenous repair; however, it often results in the formation of inferior fibrocartilaginous repair tissue. This cartilaginous tissue is vulnerable due to altered biomechanics of the subchondral bone, which raises concerns about the long-term efficacy of microfracture (Solheim et al., 2016). Therefore, secondary and more complex procedures strive to restore the hyaline cartilage, such as osteochondral autografting from the less weight-bearing periphery (mosaicplasty) and autologous chondrocyte implantation (ACI). ACI represents one of the first clinical applications of tissue engineering where a biopsy from a low-weight-bearing region is performed, and ex vivo-expanded chondrocytes are implanted in a second operation. The de-differentiation of monolayer expanded chondrocytes and potential of recovery when implanted has been a matter of debate, and matrix-based ACI techniques have been developed that use absorbable scaffolds (e.g., porcine collagen) to support the implanted cells (Makris et al., 2015). An important limitation of these techniques is the long recovery time (6–12 months) to ensure neotissue formation. The choice of articular injury treatment depends on several factors, including localization and size of the lesion, the level of activity, and the degree of associated damage of menisci and ligaments.
Tears of the fibrocartilaginous menisci require surgical intervention for nearly 1 million patients in the United States annually (Vrancken et al., 2013). For lesions located in the peripheral vascularized region of the meniscus, repair strategies such as sutures and anchors allow preservation of the meniscal tissue. However, meniscal lesions often appear in the avascular central regions, which makes them less suitable for healing and usually requires partial or (sub)total meniscectomy (Figure 1; Table 1). In some cases, further treatment with a meniscal substitute, such as an allograft or a synthetic implant, is indicated to limit OA (Vrancken et al., 2013).
Other Fibrous Musculoskeletal Tissues
Another large proportion of musculoskeletal injuries in the clinic is represented by other damaged fibrous structures, including tendons, ligaments, and the annulus fibrosus (AF). Often, degenerative pathology precedes acute trauma, and, like articular cartilage, these tissues have a limited healing capacity. One of the most common tendon injuries presented clinically is tearing of one or more of the interdigitating tendons of the rotator cuff (Figure 1). Failure of initial physical therapy or acute trauma in young patients motivates surgical repair using open or arthroscopic approaches for subacromial decompression, tendon debridement, and suture or anchor supplementation (Table 1). Still, repair is limited, particularly within the complex anatomic arrangement forming the shoulder cuff. The formation of fibrovascular scar tissue frequently leads to significant morbidity, re-ruptures, and difficulties in treatment choice.
The intervertebral discs (IVDs) are composed of the nucleus pulposus (NP), a hydrophilic proteoglycan-rich gelatinous core, surrounded by a dense fibrocartilage ring—the AF (Figure 1). The gradual progression of IVD degeneration and the extrusion of the NP through defects in the AF is a major cause for lower back pain, a leading cause of global disability (Sakai and Andersson, 2015). Available treatments are mostly symptomatic, and surgical treatments often resect the structural obstruction resulting from herniation or fuse motion segments (Table 1). However, the complex structural features of IVDs surrounded by neural elements and inflammation frequently cause a homeostatic imbalance favoring a catabolic response governed by the loss of the IVD structure, which is often followed by facet joint arthritis and vertebra deformation, canal stenosis, and even deformations. Most importantly, disc replacement with synthetic implants or fusion of the motion segment does not cure the underlying pathology of IVD degeneration (Sakai and Andersson, 2015).
According to many physicians, PRP (Platelet-Rich Plasma) has been a lifesaver for their practice, while others claimed that it helped them become passionate about medicine again. This is because not only is it 100% from the body of the patient themselves, but it is also natural and comes with pretty much no side effects. It can also be used to treat a plethora of medical ailments, to the point where no other treatment options come close.
Although the above are all fantastic and solid reasons for offering PRP therapies, there are also a couple other reasons as well.
For instance, it is extremely simple compared to other treatment options. For about 1000$ as an initial investment, you can get started with offering PRP. The equipment is relatively cheap, and it pays for itself over a relatively short amount of time.
It also is not just a passing trend, as it has been going popular for a long time and shows no signs of slowing down. The market for PRP therapies is expected to reach almost 500 million dollars within the next 10 years, or an annual growth rate of 12.5% since 2015.
Patient satisfaction is another reason. In certain situations, the satisfaction rate for patients have been as high as 95%. This shocks many of the patients, who believe, although justifiably, that they cannot reverse or halt their condition without side effects, down time, and invasive surgeries.
The time for you to start including PRP into your practice is now, while the supply is low but the demand is booming. There is still a lot more promise when it comes to PRP as well, including combining PRP with other treatments to increase efficacy. Since no standard has yet to be established, you may be starting these standards yourself.
It is vital that we get more doctors to utilize PRP therapy so that they can be a pioneer in this field. PRP can turn medicine on its head, and missing out should not be a smart option.
The best part about it, is that PRP can be utilized in almost every field and specialty, from sports medicine, to pain management, skin rejuvenation, hair care, and even urology. Most of the physicians who utilize this treatment also saw higher patient retention rates as well.
So is there a legitimate reason to not add PRP to your practice?
Despite being rather simple, PRP extraction has been shrouded with debate on the reliability of the methods for the past decade. We are going to help clear up the debate by providing information on choosing the best PRP kit.
Using a kit is in itself vital to the creation of PRP. While it is possible to draw blood into a test tube and put it through a centrifuge and claim it is PRP, it’s otherwise ineffective. This is what is known as “bloody PRP,” and it might hold 1.5x the amount of blood platelets if you’re lucky, but it will also contain a ton of red and white blood cells. Because of this, this ineffective form of PRP can potentially cause flare ups after injection.
However, if you use a kit, that concentration of platelets can be as high as 5-7 times the baseline.
What Makes A PRP Kit Good?
This concentration of 5-7 times is vital for PRP to work, and kits allow you to choose whether or not you want to keep in the red and white blood cells, or whether you don’t. Each one would work on different ailments. However, some commercial kits may not deliver what you may want in your PRP, so it is good to know the difference between the kits.
- Gel Separators
Gel separators is pretty much just a test tube with some gel on the bottom. This gel is able to separate the blood from the platelets due to osmosis. The main issue is that when the test tube goes through the centrifuge, most of the platelets will also be caught by the gel as well. This will wind up with 1.5 times concentration of platelets at most, but it does take out the white and red blood cells as well, so that’s a plus.
- Buffy Coat
The kits that allow you to see a buffy coat are most likely to give you concentrations of 5-7 times. A buffy coat is a thin layer that is formed between the blood and the plasma after being in a centrifuge. This is mainly just platelets and white blood cells, with plasma on top, and packed blood underneath.
After this, you have to be able to separate the bufy coat from the red blood cells without contamination. This will help you to get PRP with less than 10% red blood cells.
- Buffy Coat with a Double Spin
The third and final type utilize a buffy coat which is devoid of red blood cells. This is the best kit on the market, because what you do is after separating the PRP from the red blood cells, you spin it again to further get rid of the red blood cells and to concentrate the platelets even more. After this, all that is needed to do is to separate the buffy coat, and this is PRP.
The Biosafe Kit
Although there are many kits that create PRP, the Biosafe kit has to be the best on the market. This is because it give you full control over the end product. Using this machine, you wind up with 10cc of usable product, which you can then double spin for that 5-7 times concentration. You can also choose whether or not you want some red blood cells in the finished product as well.
What is Leukocyte-poor PRP?
Leukocytes are otherwise known as White Blood Cells, and some researchers believe that they can be detrimental to PRP therapy. While there is no consensus as of yet, it is believed by many that these blood cells may trigger an inflammatory response, and even prevent growth factors from creating new cells.
However, some researchers believe that white blood cells are vital to a beneficial response. They believe that without these cells, you will be left with a lot of scar tissue at the site of healing. This Leukocyte-rich PRP also tends to have much more growth factors as well.
If you want to try leukocyte-poor PRP, you will need a Leukocyte Reduction filter, also known as an LR filter. These filters use electrostatic attraction to separate the white blood cells from the rest of the PRP. Although some filters can get clogged, a CIF-LR filter will be able to prevent that and filter out 99.99% of white blood cells.
There Is Plenty Of Evidence To Back This Up
Many people are highly skeptical about PRP, and are willing to ignore it without tons of randomized double-blind studies. Ignoring that some of the things that they do in their practice is also not proven in this manner. Many refuse to even look at the evidence, including the long line of evidence since the 1970’s, ranging over 6000 scientific studies.
The best evidence is how much clients will pay for this despite not being covered by insurance. This shows without any doubt that something about this treatment must be working. As long as there are clients, Adimarket will be there to provide the equipment for practices.
Although the clinical demand for bioengineered blood vessels continues to rise, current options for vascular conduits remain limited. The synergistic combination of emerging advances in tissue fabrication and stem cell engineering promises new strategies for engineering autologous blood vessels that recapitulate not only the mechanical properties of native vessels but also their biological function. Here we explore recent bioengineering advances in creating functional blood macro and microvessels, particularly featuring stem cells as a seed source. We also highlight progress in integrating engineered vascular tissues with the host after implantation as well as the exciting pre-clinical and clinical applications of this technology.
Ischemic diseases, such as atherosclerotic cardiovascular disease (CVD), remain one of the leading causes of mortality and morbidity across the world (GBD 2015 Mortality and Causes of Death Collaborators, 2016, Mozaffarian et al., 2016). These diseases have resulted in an ever-persistent demand for vascular conduits to reconstruct or bypass vascular occlusions and aneurysms. Synthetic grafts for replacing occluded arterial vessels were first introduced in the 1950s following surgical complications associated with harvesting vessels, the frequent shortage of allogeneic grafts, and immunologic rejection of large animal-derived vessels. However, despite advances in pharmacology, materials science, and device fabrication, these synthetic vascular grafts have not significantly decreased the overall mortality and morbidity (Nugent and Edelman, 2003, Prabhakaran et al., 2017). Synthetic grafts continue to exhibit a number of shortcomings that have limited their impact. These shortcomings include low patency rates for small diameter vessels (< 6 mm in diameter), a lack of growth potential for the pediatric population necessitating repeated interventions, and the susceptibility to infection. In addition to grafting, vascular conduits are also needed for clinical situations such as hemodialysis, which involves large volumes of blood that must be withdrawn and circulated back into a patient several times a week for several hours.
In addition to large-scale vessel complications, ischemic diseases also arise at the microvasculature level (< 1 mm in diameter), where replacing upstream arteries would not address the reperfusion needs of downstream tissues (Hausenloy and Yellon, 2013, Krug et al., 1966). Microvascularization has proven to be a critical step during regeneration and wound healing, where the delay of wound perfusion (in diabetic patients, for example) significantly slows down the formation of the granulation tissue and can lead to severe infection and ulceration (Baltzis et al., 2014, Brem and Tomic-Canic, 2007, Randeria et al., 2015).
In order to design advanced grafts, it is important to take structural components of a blood vessel into consideration, as understanding these elements is required for rational biomaterial design and choosing an appropriate cell source. Many of the different blood vessel beds also share some common structural features. Arteries, veins, and capillaries have a tunica intima comprised of endothelial cells (EC), which regulate coagulation, confer selective permeability, and participate in immune cell trafficking (Herbert and Stainier, 2011, Potente et al., 2011). Arteries and veins are further bound by a second layer, the tunica media, which is composed of smooth muscle cells (SMC), collagen, elastin, and proteoglycans, conferring strength to the vessel and acting as effectors of vascular tone. Arterioles and venules, which are smaller caliber equivalents of arteries and veins, are comprised of only a few layers of SMCs, while capillaries, which are the smallest vessels in size, have pericytes abutting the single layer of ECs and basement membrane. Vascular tissue engineering has evolved to generate constructs that incorporate the functionality of these structural layers, withstand physiologic stresses inherent to the cardiovascular system, and promote integration in host tissue without mounting immunologic rejection (Chang and Niklason, 2017).
A suitable cell source is also critical to help impart structural stability and facilitate in vivo integration. Patient-derived autologous cells are one potential cell source that has garnered interest because of their potential to minimize graft rejection. However, isolating and expanding viable primary cells to a therapeutically relevant scale may be limited given that patients with advanced arterial disease likely have cells with reduced growth or regenerative potential. With the advancement of stem cell (SC) technology and gene editing tools such as CRISPR, autologous adult and induced pluripotent stem cells (iPSCs) are emerging as promising alternative sources of ECs and perivascular SMCs that can be incorporated into the engineered vasculature (Chan et al., 2017, Wang et al., 2017).
Importantly, a viable cell source alone is not sufficient for therapeutic efficacy. Although vascular cells can contribute paracrine factors and have regenerative capacity, merely delivering a dispersed mixture of ECs to the host tissue has shown limited success at forming vasculature or integrating with the host vasculature (Chen et al., 2010). Therefore, recent tissue engineering efforts have instead focused on recreating the architecture and the function of the vasculature in vitro before implantation, with the hypothesis that pre-vascularized grafts and tissues enhance integration with the host. In this review, we explore recent advances in fabricating blood vessels of various calibers, from individual arterial vessels to vascular beds comprised of microvessels, and how these efforts facilitate the integration of the implanted vasculature within a host. We also discuss the extent to which SC-derived ECs and SMCs have been incorporated into these engineered tissues.
The first reported successful clinical application of TEBV in patients was performed by Shin’oka et al., who implanted a biodegradable construct as a pulmonary conduit in a child with pulmonary atresia and single ventricle anatomy (Shin’oka et al., 2001). The construct was composed of a synthetic polymer mixture of L-lactide and e-caprolactone, and it was reinforced with PGA and seeded with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). The authors demonstrated patency and patient survival 7 months post-implant, and expanded their study to a series of 23 implanted TEBVs and 19 tissue patch repairs in pediatric patients (Hibino et al., 2010). They were noted to have no graft-related mortality, and four patients required interventions to relieve stenosis at a mean follow-up of 5.8 years. The first sheet-based technology to seed cultured autologous cells, developed by L’Heureux et al., was iterated by the group to induce cultured fibroblast cell sheet over a 10-week maturation period and produce tubules of endogenous ECM over a production time ranging between 6 and 9 months. They dehydrated and provided a living adventitial layer before seeding the constructs with ECs (L’Heureux et al., 2006). Their TEBV, named the Lifeline graft, was implanted in 9 of 10 enrolled patients with end-stage renal disease on hemodialysis and failing access grafts in a clinical trial. Six of the nine surviving patients had patent grafts at 6 months, while the remaining grafts failed due to thrombosis, rejection, and failure (McAllister et al., 2009). An attempt to create an “off the shelf” version of this graft in which pre-fabricated, frozen scaffolds were seeded with autologous endothelium prior to implantation led to 2 of the 3 implanted grafts failing due to stenosis, and one patient passed away due to graft infection (Benrashid et al., 2016).
Most recently, results were reported for the phase II trial of the decellularized engineered vessel Humacyte in end-stage renal disease patients surgically unsuitable for arterio-venous fistula creation (Lawson et al., 2016). This clinical scenario offers a relatively captive patient population in which graft complications are unlikely to be limb or life-threatening, and infectious and thrombotic event rates for traditional materials such as ePTFE are high (Haskal et al., 2010). The manufacturers seeded a 6mm PGA scaffold with SMCs from deceased organ and tissue donors and decellularized the scaffold following ECM production in an incubator coupled with a pulsatile pump prior to implantation. Humacyte demonstrated 63% primary patency at 6 months, 28% at 12 months, and 18% at 18 months post-implant in 60 patients. Ten grafts were abandoned. However, 12-month patency and mean procedure rate of 1.89 per patient-year to restore patency were comparable to PTFE grafts, while higher secondary patency rates were observed (89% versus 55%–65% at 1 year) (Huber et al., 2003, Lok et al., 2013). Although Humacyte revealed no immune sensitization and a lower infection rate than PTFEs (reported up to 12%) (Akoh and Patel, 2010), there remains much work to be done to improve primary patency and reduce the need for interventions.
Harnessing the regenerative functions reported in ECs derived from adult stem cells and iPSCs offers the promise of improving TEBV patency. Mcllhenny et al. generated ECs from adipose-derived stromal cells, transfected them with adenoviral vector carrying the endothelial nitric oxide synthase (eNOS) gene, and seeded the ECs onto decellularized human saphenous vein scaffolds (McIlhenny et al., 2015). They hypothesized that through inhibition of platelet aggregation and adhesion molecule expression, nitric oxide synthesis would prevent thrombotic occlusion in TEBV. Indeed, they reported patency with a non-thrombogenic surface 2 months post-implantation in rabbit aortas. While introducing additional complexities, engineering ECs and SMCs with other regenerative, anti-inflammatory, anti-thrombotic genes could perhaps bridge the functional difference between SC-derived cells and native primary cells.
Many clients are highly skeptical that their ailments can get better just by utilizing a few injections. Many clients may quit after a few sessions, but then return when they feel their ailments easing up. This is especially true when it comes to the practice of Rheumatology.
Rheumatology has benefited immensely from the use of PRP, otherwise known as Platelet-Rich Plasma. This is because not only is it simple to administer, but it works wonders for musculoskeletal conditions, such as joint issues, swelling, and bone issues.
If you are a Rheumatologist, you have probably used, or at least heard, of PRP therapy. This has helped many patients from having to go through surgery. However, over 27 million Americans in the osteoarthritis segment alone would have benefited more if their rheumatologist used PRP therapy.
Not All Treatments Are Successful, Here Is Why
Sometimes PRP can work, sometimes it may not, and this can differ even among the same person. However, there are some things you can do to prevent treatments from failing.
For PRP to work, the platelets present in the blood extracted has to be more concentrated than the baseline in the body. This can work by utilizing a PRP kit, which you can purchase at Adimarket. Using these kits, you can get a 5-8x the baseline, which works best for the treatments.
- White Blood Cells
PRP with white blood cells behave differently than those that do not have it. Most popular forms of PRP have these blood cells. There are three subgroups within this: Red Blood Cells, that don’t have platelets, Platelet Serum that has suspended platelets, and the Buffy Coat, which has both platelets as well as white blood cells. Adding in white blood cells can help speed up the healing process by removing bacteria and dead or dying cells.
- Using Anti-Coagulants
When making PRP, it is standard to use an anti-coagulant. This prevents the blood from clotting, but it does make the blood a little more acidic than usual. This can be detrimental on the growth factors, so adding a buffer before injection can be beneficial.
The Growth Factors Used
PRP heals wounds rather well due mostly to the growth factors that re found in blood platelets. By activating these platelets, the growth factors are able to be used by tissues and ligaments. Although the specifics are not well known, there is plenty of evidence that growth factors help with inflammation, remodeling, and even regenerating cells.
What is the clinical Evidence supporting PRP?
- PRP and Subacromial Tendonitis.
PRP has been shown to be effective in treating Subacromial Tendonitis in many studies. One study, headed by Dr. Turlough O’Donnell of the UPMC Beacon Hispital in Dublin Ireland, studied 102 patients treated with PRP while another 102 were treated with a 20mL solution of bupivacaine and 80 mgs of methylprednisolone.
After 12 months of follow-up, the PRP group were 16 times less likely to have to have invasive surgery as opposed to the other group.
This is often a chronic form of tendinopathy, and treatments are rarely effective. However, studies involving PRO have been promising. In one study, 19 patients who would otherwise have gotten surgery were given PRP treatment instead, and after 8 weeks, they saw a 60% improvement, and within two years, that number rose to 93%.
Another randomized double-blind study compared PRP with corticosteroids in 100 patients with chronic epicondylitis. The beneficial effects of PRP far outweighed the effects of the corticosteroids.
- Plantar Fasciitis
Otherwise known as Policeman’s Heel, plantar fasciitis is fairly common in the field of rheumatology. The main treatment to date would be to simply mask the symptoms by using corticosteroids. However, one study showed that PRP was much better than corticosteroids after a 3 month followup.
- Knee Osteoarthritis
PRP therapies for osteoarthritis of the knee have been studies intensively in the past few years. These studies have shown a lot of promise for this therapy. One systematic review showing a total of 1543 participants showed that PRP therapy fares better than hyaluronic acid when it comes to improving knee joint cartilage.
How PRP can Benefit Rheumatology
PRP is not just a passing trend, and is here to stay, and may be the most useful tool for rheumatologists. With no other treatments coming close to its safety, efficacy, or simplicity, It is a shame that it is not more common than it currently is. Since this therapy carries no risk, there is no reason to at to not at least give it a try.
Trying it is relatively inexpensive, and will pay for itself over time. Adimarket will be happy to supply you with kits, and even a standard lab centrifuge.
We need more rhumatologists to utilize PRP and help patients forgo intrusive surgeries. This will be beneficial for over 27 million Americans. Besides, since it is a new treatment option, getting into the field early will make you a pioneer in the field, which will benefit your practice immensely.
Thousands of skincare centers across the nation provide at the very least one kind of PRP treatment. However, most do not go any farther than micro-needling with a topical solution. This is mainly because it is far simpler than all other methods, and it is incredibly popular. However, it would make more sense to many practices who have invested in equipment for add in PRP injections as well.
PRP Is Growing Substantially
Regardless of what is being treated, the protocol for obtaining PRP is the same: You draw the blood, place it in the centrifuge, and then take out the PRP from the rest of the material. This simplicity can be combined with PRP’s vast usability to create significant and mindblowing advances in modern medicine.
This includes skincare as well, as the PRP that you get from patients can be used in a plethora of ways. Here are a couple of examples of what can be performed by dermatologists and plastic surgeons the world over.
- Skin Augmentation
Adding a topical solution of PRP ccombined with microneedling can help to regenerate dying skin cells, and makes skin feel soft. Although this will probably work for most clients, many might want more. For instance, if you want to plump up the face, injecting PRPinto the dermis can help provide both beauty, as well as a healing process.
Although if you want to create volume, you will need a filler. One way to do this is by using a Platelet-Poor Plasma filler, or PPP, which is often left over from the PRP process. You can also use Hyaluronic Adic. A combination of these with PRP have been known to provide wonderful results, with some clinicians boasting a 100% success rate.
- Vitiligo Correction
Many companies will shill out millions of dollars to find out how to turn defective cells healthy again. Many are looking into DNA Technology. However, simply utilizing PRPP may provide the same results. Some studies have shown that adding CO2 laser therapy for correcting vitiligo to a PRP treatment can increase it’s effectiveness by 4 times. This can also be beneficial in other areas, such as correcting wrinkles, and even acne scars. So combining PRP treatments are conventional therapies can boost the effects tremendously.
So if PRP can help boost the effects of lasers, it may be able to also boost the effects of other skin therapies as well. It seems like a great opportunity to continue doing the work that you do, but this time it is more effective due to a simple method. This is something that hundreds of skin care facilities are already providing for their clients.
- Hair Rejuvenation
Mesotherapy is a common treatment that utilizes microinjections that deliver a medication throughout the skin’s service. This prodecure has been able to provide great quality results by adding peptides and vitamins to the mix as well. However, one of the best ways that you can incorporate this into your practice is by using PRP therapy.
Mesotherapy can also be used to provide an even amount of PRP all over the body, including face, neck, hands, etc. This helps to rejuvenate the skin and reduce wrinkles, discoloration, and stretch marks. However, this works best when it comes to hair loss treatments. In fact, adding PRP with mesotherapy has exceeding the expectations that the industry has set.
This is why we think PRP therapy is something that every skincare clinic should offer. Since hair loss effects both men and women, it is important to try to work to make your treatments as effective as possible. Your patients will benefit from it and satisfaction will rise, is there any other reason to put it off?
“But I Never Heard Of Them!”
Some of these treatments and combinations are incredibly new, so new, that many might not have heard of them before. However, this is why signing up to use them as soon as possible is vital. This way, you can bee a step ahead of the competition when it comes to providing great services.
The demand for PRP is only growing over time, and the sooner you can get on board, the better off your practice will be. If you are interested in learning more about PRP therapy, or checking out our line of PRP equipment, you can do so by going to the Adimarket website and checking it out for yourself.
PRP provides more effective treatments for less time, less money, and more satisfaction. Tons off practices have been putting their trust in this treatment and have been reaping the benefits long term. PRP is here to stay, so are you ready to seize the potential of this great medical revolution?,
PRP is a powerful means of regenerating tissues, and has pretty a pretty large growth in popularity among patients, especially those who suffer from alopecia. This is despite the apparently lack of evidence that supposedly surrounds the treatment.
Is It A Lack Of Evidence Or Just A Lack Of Funding?The lack of widespread research may have more to do with funding than anything else. Many of the studies that are currently out there about PRP were unfunded, especially on the subject of Hair Regeneration. However, despite this lack of funding, the demand for PRP treatments for hair loss is growing at an unprecedented rate.
When it comes to PRP kits, there are three kinds to choose from. Ones that use gels, one that create a buffy coat, and one that creates a buffy coat utilizing a double spin. It is pretty unanimous that the last option creates the most reliable and concentrated form of PRP possible, at 5-7 times the baseline amount of platelets.
This concentration level also has the most nutrients which helps for the regeneration of blood vessels and stem cells. One commonly recommended tactic is to combine PRP hair regeneration with micro-needling with a topical layer of PRP. This may be beneficial in some cases.
Micro-needling is a way to create small amounts of trauma, which the body reacts to via a healing response. This response, mixed with PRP, can help to stimulate the growth of new cells.
In some instances, a dermatologist might have three sessions, with the first two being PRP injections, and the middle one being a micro-needling with a PRP topical solution. However, micro-needling is completely optional. Whether you choose to use this method or not, you will still be injecting the patient with PRP at the scalp.
Combining PRP with an Allograft Matrix
One thing that many hair regeneration experts do is combine PRP with an Allograft matrix. These are often used when healing wounds, as it changes inactive adult stem cells back into an active form. This makes the wounds heal faster.
This is because an allograft acts like a scaffold that proliferates cell regrowth and speeds up the healing process. Many experts in the fields have noted a high degree of success by using this method.
Allografts are generally made from using the bladder tissue of pigs. However, a better type of allograft is made from amniotic tissues and fluid. This type of allograft can be utilized with little or no chance of being rejected by the body, as opposed to those made from pig bladders.
Medications Vs PRP
The main drugs that are commonly used to regrow hair are Minoxidil and Finasteride. These were designed to be able to prevent male pattern hair loss, but did almost nothing when it came to regrowing lost hair. However, these drugs have been well known to only be temporary solutions, and if the patients stopped taking the drugs, the benefits of them would quickly reverse. These are also not 100% effective at stopping hair loss either, but it can slow the progression.
However, PRP is different. It may actually be the only treatment on the market that has been clinically proven to regrow hair and heal hair follicles. This means that it only only slows down hair loss, but actually helps with hair growth.
Many may ask how temporary the solution is, saying that the other drugs on the market are just temporary solutions. However, many pateints report that a PRP and allograft combination treatment was able to give them great results that lasted for nearly half a decade or more with just one treatment. However, each patient is indeed different.
Aside from drugs, we only had one other choice when it came to hair loss, and that was hair transplants. This is why PRP has been growing in popularity in hair regrowth groups lately. Although those other treatments are not obsolete in the slightest, adding PRP therapy can be both beneficial and safe to patients in the long run.
Some people combine the two, and use PRP alongside Minoxidil and Finasteride with little to no side effects seen to date. You can even combine PRP with laser light scalp stimulation therapy, but that is up to you.
So Try It Out
PRP for hair regeneration, skin rejuvination, and even facelifts is going strong with no sign of stopping. Many dermatologists have already taken the plunge, and since this treatment is not going anywhere anytime soon, it may behoove you to join in on it too.
For more information about PRP including equipment, check out the Adimarket website. We provide great tools for any practice to utilize.
Global Stem Cells Group Advisory Board Member Amine Rafik, M.D., Ph.D. to speak on the Role of Adipose-Derived Stem Cells in Wound Healing, at the ISSCA Regenerative Medicine Cell Therapies Symposium in Istanbul, Turkey
MIAMI, Feb 19, 2018—Amine Rafik, M.D., Ph.D., a member of the Global Stem Cells Group Advisory Board, will be a keynote speaker at the International Association for Stem Cell Application (ISSCA) Regenerative Medicine Cell Therapies Symposium in Istanbul, Turkey April 28, 2018. Rafik will speak on the role of adipose-derived stem cells in regenerative medicine as an attractive alternative to the use of stem cells derived from bone marrow and other sources, due to their abundance in fat and their ability to be easily harvested.
Rafik’s lecture will include patient demographic data and digital photographs taken on the day of each patient’s surgery and every day thereafter. ASC patients received three treatments of 20 cc of autologous adipose stem cell injections in the subcutaneous tissue surrounding the ulcer with time to wound closure defined as the time at which the wound bed was completely re-epithelialized and filled with new tissue.
He will discuss study results revealing the average time for wound closure in adipose stem cell (ASC) recipient patients compared to control group patients. He will also examine the study’s conclusion that suggests local transplantation of autologous adipose stem cells could accelerate wound healing, and that some clinical aspects of wound healing, as well as the potential for therapies based on stem cells, represent a feasible therapeutic approach to the treatment of clinical wounds.
Rafik is a consultant and plastic, reconstructive and aesthetic surgeon at Al Farabi Hospital in Morocco. He specializes in reconstructive plastic surgery particularly for the face, head, and neck, as well as for patients who require reconstructive surgery following treatment for skin cancer or trauma. Rafik also performs cosmetic surgery and microsurgery.
He completed his plastic surgery training in Casablanca and was awarded full membership to the American Academy of Cosmetic Surgery in 2015, and the European Association of Maxilla-Facial surgery in 2016.
He is a reviewer for many international indexed journals, including; OncoTargets and Therapy Journal, the British Journal of Medicine and Medical Research, and the Cancer and Clinical Oncology Journal, published by Canadian Center of Science and Education, where he is a member of the editorial board.
The Istanbul international symposium is part of ISSCA’s mission to support a paradigm shift from traditional healthcare solutions to regenerative medicine and provide the latest innovative discoveries and developments in all areas of stem cell research. The symposium will host a group of renowned international speakers, experts in the field of stem cell and regenerative medicine, who will provide a full day of rigorous scientific discourse directed to physicians.
The day’s events will incorporate information on stem cell biology, medicine, applications, regulations, product development, and commercialization, business opportunities, challenges, and potential strategies for overcoming those challenges.
To participate in the ISSCA Istanbul Symposium, reserve your spot by registering today.
For more information, visit the stemcellconference.org website, email email@example.com, or call +1305 560 5337.
About International Society for Stem Cell Application (ISSCA):
The International Society for Stem Cell Application (ISSCA) is a multidisciplinary community of scientists and physicians, all of whom aspire to treat diseases and lessen human suffering through advances in science, technology and the practice of regenerative medicine. ISSCA serves its members through advancements made to the specialty of regenerative medicine.
The ISSCA’s vision is to take a leadership position in promoting excellence and setting standards in the regenerative medicine fields of publication, research, education, training, and certification.
As a medical specialty, regenerative medicine standards and certifications are essential, which is why ISSCA offers certification training in cities all over the world. The goal is to encourage more physicians to practice regenerative medicine and make it available to benefit patients both nationally and globally. Incorporated under the Republic of Korea as a non-profit entity, the ISSCA is focused on promoting excellence and standards in the field of regenerative medicine.
ISSCA conference speaker Amine Rafik