Soon to be released by Springer Publishing – Regenerative Treatments in Sports & Orthopedic Medicine
Marko Bodor, together with colleagues Sean Colio and Ryan Dregalla, is contributing an important chapter in the forthcoming book, “Regenerative Treatments in Sports & Orthopedic Medicine”, to be published by Springer Publishing in September 2o17.
Chapter 9: Amniotic and Umbilical Cord Products, Alpha-2 Macroglobulin, and Interleukin-1 Receptor Antagonist Protein
In this chapter we review three emerging areas in regenerative medicine for orthopedic conditions:
amniotic products, interleukin- 1 receptor antagonist protein ( IRAP ), and alpha- 2 macroglobulin (A2M ). Amniotic fluid and membranes contain numerous growth factors, cytokines, anti-inflammatory proteins, collagen, fibronectin, mesenchymal stromal cells, epithelial cells, and hyaluronic acid. These components are appealing for their utility in treating various acute and chronic musculoskeletal pathologies. IRAP is a naturally occurring analog and a competitor of interleukin- 1 (IL-1) and binds to the interleukin- 1 receptor (IL-1R) causing suppression of inflammation typically caused by IL-1. By suppressing the IL-1 inflammatory cascade, it may be possible to prevent the activation of macrophages, monocytes, and stimulation of osteoclasts that break down bone and cartilage matrix in orthopedic injuries and degenerative processes. A2M is a plasma glycoprotein with
a unique ability to inhibit metalloproteinases (MMP) involved in degrading cartilage and inflammatory cytokines production. Similar to IRAP , A2M may help reduce the catabolic process in degenerative and inflammatory orthopedic conditions. Throughout this chapter we also review the current clinical evidence regarding the use of these techniques.
The majority of studies investigating the use of amniotic products, IRAP , and A2M are limited to in vitro and animal studies with few human clinical trials. Additional randomized clinical trials including other musculoskeletal pathologies along with larger sample sizes and longer term follow- ups are needed to understand their future potential. Furthermore, most of the trials have compared their efficacy versus corticosteroids and saline rather than other orthobiologics. Corticosteroids have known
dose- dependent side effects with risks, including osteoporosis, osteonecrosis, deterioration of articular cartilage and tendon or ligament weakening or rupture leading to minimizing their chronic usage and in some cases avoiding them altogether. Intra- articular saline injections have been shown to yield a statistically and clinically meaningful improvement in knee OA symptoms for up to 6 months, which exceed a placebo effect (102). Therefore, a more logical comparison would be evaluating these products versus other regenerative medicine techniques, such as HA, platelet- rich plasma, or MSC. Nonetheless, improvements have been made in the production and isolation of these products allowing this research to advance, a great stride forward when compared with the early use of bovine amniotic fluid in the joints of patients described in 1938.
ABOUT THE BOOK
Regenerative medicine offers physicians new tools to help repair damaged tissue, alleviate pain, accelerate healing, and improve function for patients with degenerative conditions or sports injuries. Regenerative Treatments in Sports and Orthopedic Medicine is the first comprehensive book devoted to orthobiologic treatments for orthopedic conditions. Authored by experts in regenerative medicine, this evidence- and experience-based guide is written for clinicians looking to understand and effectively implement these treatments in their practices.
Broad yet focused coverage of the scientific underpinnings, regulatory issues, staffing and equipment, nutritional and rehabilitation concerns, and orthobiologic interventions for specific clinical problems make this the ideal procedural reference for anyone working to restore function to athletes or other patients with musculoskeletal pathologies.
- Unparallelled coverage of clinical science and practical applications
- Written by pioneering leaders at the forefront of an emerging standard of care
- Evidence-based indications for initiating orthobiologic therapies
- Includes a review of important nomenclature for the novice
- Covers both Platelet Rich Plasma (PRP) and stem cell procedures
- A must-read guide for practitioners in academic and private practice settings
PRE-ORDER YOUR COPY HERE: www.springerpub.com/regenerative-treatments-in-sports-and-orthopedic-medicine.html
The 25th Annual Meeting of the Spine Intervention Society
July 19 – 22, 2017 San Francisco Mariott Marquis
General Session : Regenerative Medicine
Learn the latest information about the rapidly expanding field of regenerative medicine. The speakers discuss the latest research and the clinical use of stem cells, bone marrow aspiration concentrate, platelet-rich plasma (PRP), amniotic tissue, and alpha-2-macroglobulin in the interventional spine field. The use of these therapies in clinical practice is also debated.
About the SIS:
The Spine Intervention Society (SIS), formerly known as the International Spine Intervention Society, has spent the last 25 years developing and promoting the highest standards for the practice of interventional procedures in the diagnosis and treatment of spine pain. Our Society is driven by leading multi-specialty physicians who are dedicated to advancing awareness of the implementation of evidence-based spine interventions through practice, advocacy, research, and education. With over 2,600 members, the Society comprises physicians from multiple specialties: Anesthesiology, Physical Medicine and Rehabilitation, Radiology, Neurology, Orthopedic Surgery, and Neurosurgery.
ESSENTIALS OF REGENERATIVE MEDICINE IN INTERVENTIONAL PAIN MANAGEMENT
PRP: History, Mechanism of Action, Preparation and Clinical Applications
By Dr. Marko Bodor, MD; Ryan Dregalla, PhD; and Yvette Uribe, BA
Platelet Rich Plasma (PRP) was first described for clinical use in 1999 to enhance osseointegration for tooth implants well after specific individual growth factors had already been identified for healing of various wound and injury types. The therapeutic importance of platelets became clear when they became better characterized, acting as reservoirs for a wide array of bioactive factors, growth factors, adhesive proteins, coagulation factors, cytokines and chemokines released in the presence of appropriate stimuli and orchestrated in the progression of wound repair. Hence, it was logical to assume that if platelets and their bioactive factors were concentrated and delivered to an injury site, the healing process could be enhanced and expedited.
Soon after being described for oral surgery, PRP was used in veterinary and sports medicine. In 2006, Mishra and Pavelko reported on PRP as an alternative to surgery for chronic tennis elbow.In the last decade the deleterious effects of corticosteroids on tendons and cartilage have become increasingly more recognized and interest in PRP for the treatment of neuromuscular, musculoskeletal and orthopedic conditions has increased exponentially with over 700 peer-reviewed articles referenced on PubMed in 2016.Many “next generation” platelet products, including platelet-rich fibrin, leukocyte-rich or -poor PRP, platelet lysate, post-platelet degranulation serum and extracts have been developed.
Mechanism of Action
Platelets are anuclear 2-3 µm diameter fragments of megakaryocytes from the bone marrow and contain an abundance of growth, chemotactic, and clotting factors. Platelets are capable of adhering to and pulling together torn tissue using their tentacle-like filopodia with an internal network of actin and myosin. PRP is simply a platelet concentrate, platelets in plasma concentrated 3-5x or higher than in whole blood.
Platelets need to become activated in order to adhere to collagen and release their growth factors. Platelet activation depends on external stimuli such as thrombin, ADP, calcium or the presence of certain structural proteins that are not present in the endothelium such as collagen.Platelets adhere to soluble factors, extracellular matrices and other platelets. Platelet degranulation involves the fusion of alpha and dense (delta) granules to their membranes with release of growth and anabolic factors.
Platelet degranulation results in inflammation,recruitment and proliferation of several cell types including leukocytes (days 0-2),promotion of neovascularization (days 2-3), migration and division of fibroblasts, synthesis of collagens type I and III and new tissue formation (days 3-5). PRP may help repair or regenerate tissue, especially in poorly vascular regions where platelets are not already present.
Pro-Inflammatory and Catabolic Pathway
Within minutes of activation, platelets release platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta-1 (TGF-B1), interleukin 1B (IL-1B), adenosine diphosphate (ADP) and histamine. These factors stimulate leukocytes to release inflammatory cytokines (IL-1B, TNF-α, IL-6) enhance the expression of degradative enzymes of the matrix metalloproteinase (MMP) family and prepare tissue for repair and regeneration. How much platelet-leukocyte interaction is necessary at the site of injury to optimize healing is not known. When leukocytes are increased at the site of injury, PRP will have more of an inflammatory effect. However, platelets alone may be all that is necessary to repair tissu.
Anti-Inflammatory and Anabolic Pathway
Upon degranulation platelets release growth factors over a period of days. These are later accompanied by other growth factors secreted by the leukocytes This process reduces inflammation, restores the environment to an anabolic state, and may be part of the pain-relieving effect of PRP.
Platelet related growth factors and neovascularization stimulate fibroblast homing and proliferation in tendons and ligaments Fibroblasts orient at the site of injury marked by platelet aggregates and neovessels and synthesize collagen. For hyaline cartilage injuries, neovascularization does not occur because the appropriate precursor (endothelial) cells are lacking Fibrocartilage fills these defects days to weeks after injury, but does not have the durability of hyaline cartilage.
Mechanical Functions of Platelets
Lam et al have extensively studied the mechanical properties of platelets Platelets are capable of adhering to and pulling together torn collagen using tentacle-like filopodia and an internal network of actin and myosin, the same contractile proteins in skeletal muscle. Platelets are able to generate a dynamic force of 29 nN and a static force of 70 nN, approximately 1/3rd that of slow twitch muscle fibers, Therefore it may be possible to use platelets to close small defects in tissues similar to how sutures are used in surgery.
PRP preparation begins with the collection of whole blood mixed with an anti-coagulant such as heparin, sodium citrate or citrate-dextrose, allowing cells to remain in suspension, followed by centrifugation for several minutes. There are three basic fractions of centrifuged whole blood: 1) the red blood cell fraction, always the densest, collecting at the bottom, 2) the buffy coat, containing white blood cells and possibly platelets, and 3) the plasma fraction, containing some degree of platelets. Where platelets settle depends on centrifuge time and force. The goal of most PRP preparations is 1 million platelets/µl .
Centrifugal Forces and the Composition of the Plasma and Buffy Coat Fractions
Centrifugal forces commonly used are 100 – 700 x gravity (x g with spin times on the order of 5 – 20 minutes. There is an inverse relationship between force and spin time – the higher the force the lower the spin time and vice-a-versa. A standard objective in producing PRP has been to concentrate platelets into a small volume with the count per microliter (µl) being several times (e.g. 5x) higher than in whole blood. Several years ago many preparations focused on increase over baseline concentration alone, however it has since been recognized that this is only one aspect affecting the quality and characteristics of PRP.
In systems using high centrifugal forces, leukocytes and platelets are concentrated in the buffy coat. Furthermore, this results in a high concentration of red blood cells due to the poor resolution of the interface between the buffy coat and the red blood cells. The final product is generally a red color indistinguishable from whole blood but possesses a high concentration of leukocytes and platelets (≥5x over baseline) and is known as leukocyte-rich PRP (LR-PRP).
Alternatively, lower centrifugal forces can be used over longer periods of time, allowing platelets to remain in suspension and leukocytes to collect at the red blood cell interface. In this case, aspiration of the entire plasma fraction results in PRP with a platelet concentration approximately 2x higher than in whole blood. This is due to the simple fact that red blood cells, comprising approximately 50% of whole blood, are left out. Furthermore, leukocytes within the buffy coat are also left behind, resulting in a relatively pure platelet product
However, many clinicians seek to achieve higher platelet concentrations than just 2x over baseline. To achieve this, the plasma fraction undergoes an additional centrifugation step to concentrate the platelets from the suspension into a pellet at the bottom of the container. This pellet is then re-suspended in a variable volume of plasma depending on the final desired concentration. This preparation is referred to as leukocyte-poor PRP (LP-PRP).
The differences between LR-PRP and LP-PRP are becoming better understood. These include higher inflammation and catabolic activity of LR-PRP and more anabolic and anti-inflammatory activity of LP-PRP, however, the anabolic processes of LP-PRP may favor the formation of fibrotic tissue. Both LR-PRP and LP-PRP possess anti-microbial and bactericidal properties
In an attempt to release the contents of platelets into solution, many aim to create platelet lysates. The method generally incorporates one or more freeze-thaw cycles of whole PRP at -20°C or -80°C. It has been demonstrated that PL is a viable source of growth factors above that of serum and increases cell growth when added to culture.This is viewed as an alternate version of PRP providing elevated levels of readily available growth factors that do not depend on platelet activation and degranulation.
Activation-State of Platelets
Regardless of how it was made, PRP can be injected in a “non-activated” or “activated” state. Non-activated PRP is injected as is, whereas activated PRP is injected following the addition of ADP, calcium or thrombin, or exposure to hypothermic conditions or extracellular stimuli such as collagen or glass.The latter methods serve to increase platelet sensitivity to degranulation and immobilization via adhesion. The aim of activation is to better enable platelet adhesion and delivery of growth factors to the site of injury immediately upon injection of PRP. We are unaware of in-vivo studies comparing activated versus non-activated PRP for musculoskeletal applications, although a recent study on alopecia showed no difference.
Non-activated PRP Preparations
In situations where fluidity and extended handling times may occur, PRP is injected without activation. The PRP remains as a simple concentrate and the platelets will not clot or release their growth factors right away. However, in the presence of extracellular matrices such as collagens which are major platelet activators and typically present at sites of injury, platelets will begin to degranulate. The question remains whether platelets releasing their growth factors over a period of time or right away hold any distinct advantage.
Activated PRP Preparations
Platelet activation can be achieved enzymatically, via soluble factors or by interacting with certain matrices/surfaces. Enzyme-induced activation uses thrombin at physiological or supra-physiological levels to cleave protease-activated receptors on the surface of platelets Thrombin is an irreversible, potent activator of platelets resulting in a strong intra-platelet signal for degranulation. Thrombin cleaves fibrinogen and polymerizes fibrin to produce an insoluble clot that binds and encapsulates platelets in the local vicinity. Use of thrombin to activate platelets requires that the PRP be injected immediately or else might clot and fail to pass through the needle.
Other platelet activators include calcium chloride, ADP, hypothermic conditions, and activating surfaces such as glass or collagens, but still rely on the intermediate steps of the enzymatic activation pathway, occurring downstream of thrombin-induced activation. Calcium mediates platelet granule tethering to the outer membranes and release of contents into the extracellular space ADP interacts with the P2Y1 and P2Y12 platelet surface receptors, stimulating the release of calcium from intraplatelet stores and promoting granule fusion. Calcium and ADP are thus synergistic. Hypothermia to less than 28°C has also been shown to weakly promote platelet activation, is ADP-dependent and a popular adjunct for platelet activation.Finally, collagen and negatively charged glass can be used to stimulate platelet aggregation and activation Depending on how they are activated, platelets release their growth factors differently and the optimum sequence of release is not known.
Platelet-rich fibrin (PRF) production relies on the collection of whole blood without anticoagulant, followed by a single centrifugation step for about 8 minutes at 200 x g. The result is a three-fraction blood product, as with PRP, but with the activation of clotting factors. As a result all three layers, the plasma, buffy coat and red blood cell fraction, are fixed in a fibrin matrix. The resulting PRF, consisting of the plasma fraction or plasma + buffy coat, can be extracted by cutting away the red blood cell fraction. PRF is equivalent to a 2-fold concentrated activated leukocyte-rich PRP product known to release an abundance of growth factors and which has an innate biological scaffold (fibrin PRF can easily be implanted into a surgical site, but because of its density cannot be injected unless homogenized.
Ligaments and Fibrocartilage
One of the most rewarding applications of PRP in interventional pain practice involves the treatment of ligament or fibrocartilage injuries, particularly those discovered using the skilled application of high-frequency diagnostic ultrasound. We have thus diagnosed and successfully treated chronic (and acute) hip labrum tears using LP-PRP activated with calcium chloride 10% (0.3 per 1 ml PRP) and injected into the gap of the tear (0.5 ml), above it (1 ml) and into the joint (2 ml). The calcium chloride enhances platelet aggregation in the setting of plasmin, which inhibits platelets and is in the joint fluid.
We have also had good results injecting PRP into non-displaced meniscus tears (e.g. 0.5 ml into tear, 1 ml peripheral to meniscus and 3 ml into joint, activated LP-PRP). Urzen and Fullerton reported on a case of an acute displaced bucket-handle tear reduced manually and treated with 3 injections of PRP The tear healed completely as seen on follow-up MRI and arthroscopy. Pujol et al showed improved pain, function and MRI signal in peripheral meniscus tears treated with PRP and mini-open repair versus mini-open repair alone
Podesta et al achieved high rates of return to play in 34 partial ulnar collateral ligament (elbow) injuries. Seijas et al injected PRP into partially torn anterior cruciate ligaments in a series of 19 professional soccer players, all of whom experienced improvement of stability as confirmed on KT-1000 testing and 16 returning at an average of 16 weeks after treatment It is important to note that PRP during arthroscopic surgery has not been shown to significantly improve outcomes, perhaps because circulating fluid dilutes the PRP, washed off adhesion factors on target tissues, or plasmin within the joint fluid inhibits the formation of a fibrin matrix.
In our experience, PRP is a highly effective treatment for partial tendon tears and tendinosis, but evidence-based reviews show comparable efficacy for a variety of other treatments including eccentric strengthening, needling and whole blood injections Sadoghi et al reviewed 150 studies and analyzed 14 high quality ones in animals and humans and concluded that PRP for Achilles tendinopathy has a medium to large positive effect for tendon tears but not for tendinosis.
In a double-blind randomized controlled multi-center trial, Mishra et al needled the common extensor tendons with and without PRP in 230 patients with chronic lateral epicondylitis At 6 months, 84% of the PRP and 63% of the needle only group had resolution of symptoms. Mishra’s study, like a number of others, did not separate patients with tears from those with tendinosis. For gluteus medius and minimus tendinosis, Jacobson et al found no significant difference between needling with PRP and without with 79% and 71% respective improvement at 3 months.
Fitzpatrick et al’s meta-analysis of 8 high quality studies concluded there was good evidence to support a single ultrasound-guided injection of LR-PRP for tendinopathy Fitzpatrick et al endorsed LR-PRP over LP-PRP on the basis of more studies having been done with LR-PRP as opposed to LP-PRP. The single LP-PRP study they reviewed showed improvement of pain from 7.5 to 1.2 in the 15 patients injected with LP-PRP versus 7.5 to 4.1 in 10 injected with bupivacaine at 6 months follow-up.We hope future clinical trials will compare LR-PRP to LP-PRP for tendinopathy, especially since in-vitro studies have shown that leukocytes reduce tendon matrix synthesis and promote catabolism
In our experience some tendons respond better to PRP than others depending on location and geometry. The common extensor tendon of the forearm, which has a broad attachment area, responds better than the common flexor tendon, which has a small attachment area. Tears of the rotator cuff of the hip respond better than tears of the rotator cuff of the shoulder, probably because of less tension and no adjacent joint fluid. When injecting tendons it is important to note that the needle should be visualized in two ultrasound planes to ensure injectate flows where intended. Tendons previously injected with corticosteroids or other destructive agents are less likely to respond to PRP and repeat injections might be necessary. In general, we expect significant improvement within 4-8 weeks of a single injection.
Joints and Cartilage
PRP is variably effective for osteoarthritis (OA) in our experience, in some cases resulting in long-term relief and in others not being effective at all. Typically mild to moderate improvement is seen, better and longer-lasting than with hyaluronic acid or corticosteroid, but temporary, on the order of months to a year. Results vary depending on location, with knees responding better than hips. In some cases it may not be the arthritis that is causing pain but an associated injury to the meniscus, a collateral ligament or fibrocartilage such as the hip labrum. In these cases, treating the associated injury may result in long-term resolution of symptoms and possible healing. Cartilage defects are not thought to be capable of significant healing and the primary benefit of PRP likely involves reduction of inflammation.
For knee OA, Riboh et al reviewed 6 randomized controlled trials (RCT) and 3 comparative studies on PRP LP-PRP was used in 6 studies and LR-PRP in 3; hyaluronic acid was used in 6 studies and placebo injection in 3. Riboh et al concluded that studies using LP-PRP resulted in improved pain and function compared to placebo, hyaluronic acid and corticosteroid.
Xu et al performed a meta-analysis of 10 studies on PRP for knee OA, but did not consider that LR-PRP and LP-PRP might result in different outcomes On the basis of the 2 best performed studies using LR-PRP, they concluded that PRP in general was not better than hyaluronic acid (HA). They attributed the positive outcomes of the other studies using LP-PRP to inadequate blinding of subjects and therefore a possible placebo effect.
For hip OA, Dallari et al randomized patients to PRP lysate, hyaluronic acid (HA) and PRP lysate + HA groups, showing the best outcome in the PRP lysate group, whose VAS scores improved from 3.5/10 to 1.4/10 at 3 months, rising to 2/10 at 1 year. By contrast, Battaglia et al, using PRP-lysate with an average leukocyte level of 8300/μL, showed no difference between PRP-lysate and HA and DiSante et al showed better outcomes with HA than PRP at 4 months.
For ankle OA associated with tibia vara and cross-leg sitting positions in Japan, Fukawa et al performed 3 LP-PRP lysate injections at 2 week intervals with reduction of pain from 6/10 to 2.5/10 for early and 4/10 for late stage disease at 3 months with maintenance of improvement in both groups at 6 months For moderate to advanced ankle OA, Repetto et al noted reductions of pain from 7.8+0.5 to 2.6+2.2 at an average of 17 months following a series of 4 weekly LP-PRP ankle injections For osteochondral defects of the talus, Mei-Dan et al compared LP-PRP to HA, noting improvements pain and function on the Ankle-Hindfoot scale from 66 to 98 and 66 to 78 respectively at 7 months.
For OA of the thumb, 2 intra-articular autologous conditioned plasma (2.4x LP-PRP) injections to the trapezium-metacarpal and scaphoid-trapezium-trapezoid joints spaced 4 weeks apart reduced pain from 6.2 + 1.6 to 4.0 + 2.4 at 3 months and 5.4 + 2.2 at 6 months.
Bone and Muscle
Hsu et al reviewed the evidence for PRP for spine and ankle fusions and bone in general and found no evidence that PRP is of benefit, even in conjunction with bone grafts We believe this is because bone is highly vascular, and in the case of surgery when bleeding and platelets are already present, the addition of more platelets does not add much. The same reasoning would apply to muscle. Colio et al performed a review on PRP injections for muscle and concluded that most of the published evidence, including one Level I study, indicates that PRP does not significantly benefit muscle injuries
Intervertebral Discs and Spine
Bodor et al provided a scientific rationale for PRP for intervertebral discs, given that it worked well for tendon tears and the fact that platelets have mechanical properties enabling them to pull together torn collagen. In 35 patients with lumbar and thoracic annular tears, degeneration and disc pain confirmed via anesthetic discography a week or two prior, they injected 1-2 ml of LP-PRP and noted good (reduced pain medications, improved function) to excellent (resolution of pain) outcomes in approximately two-thirds of patients at 4 to 8 weeks.13 In a double-blind RCT, Tuakli-Wosornu et al performed discography using radiographic contrast with (29 patients) and without (19 patients) LR-PRP, noting significant improvements in pain, function and patient satisfaction in the PRP group at all time points from 8 weeks to 1 year and beyond No studies have yet shown that disc height or hydration improves as a result of PRP treatment. In 46 patients with lumbar facet pain confirmed via fluoroscopically-guided intra-articular anesthetic injections, Wu et al did a RCT of LR-PRP versus corticosteroid showing improvement in both groups at 1 month but only the PRP group at 6 months.
Nerves and Neuropathic Pain
We have been surprised how often some patients (e.g. overweight 70 year old with chronic posterior ankle pain, tendinosis and tearing of the tibialis posterior) respond to PRP much faster than expected (3-5 days), with substantial improvement of pain and function before healing could have occurred. This has led us to thinking about the biologic purpose for pain. We believe there are three main reasons: 1) intrusion alert (e.g. thorn, mosquito) 2) harm avoidance (e.g. do not put hand in fire), 3) guide to healing (e.g. splint a fracture, reduce weight-bearing). With regard to the “guide to healing,” pain guides the organism to optimize the internal and external environment for healing. PRP injected at the site of injury might optimize the environment for healing. When this occurs there is no further purpose for pain, and nociceptors at the site of injury reduce or turn off the pain signal.
Kuffler has written extensively on PRP and neuropathic pain and hypothesized that PRP may help reduce neuropathic pain and neurogenic inflammation by optimizing the environment at the location of the severed nerve ends or neuroma. Kuffler et al have also been able to successfully eliminate pain in a patient with a chronic ulnar nerve injury by surgically freshening the nerve ends, placing them on both sides of a collagen tube and injecting LR-PRP within the gap Within 3 months, the patient’s chronic neuropathic pain resolved and a year later he had improvement of sensation and motor function.
In several patients with chronic neuropathy and neuropathic pain, we hydrodissected LP-PRP and LP-PRP-lysate around the ulnar nerve at the elbow without benefit. By contrast, Uzun et al found PRP to be helpful for carpal tunnel syndrome. The difference may be attributable to two primarily different etiologies, with the former being a compression neuropathy and the latter being an entrapment neuropathy caused by increased pressure within the carpal tunnel due to synovitis and swelling of flexor tendons. PRP may reduce synovitis and swelling of the tendons and pressure within the carpal tunnel and around the nerve.
Nerves have a good blood supply and in theory should not significantly benefit from additional platelets or growth factors. Further research will need to be done to determine the role of PRP for nerves and neuropathic pain.
PRP has become increasingly popular in sports, rehabilitation and pain medicine. There are at least 6 Level I studies for osteoarthritis of the knee showing improvement of pain and function following a single or a series of LP-PRP but not LR-PRP injections. There are at least 8 Level I studies showing efficacy for LR-PRP and one for LP-PRP for tendinopathies. One meta-analysis found PRP to be effective for Achilles tendon tears but not tendinopathy, but most clinical trials have not differentiated outcomes for patients with tears from those with tendinopathy.
PRP is promising for ligament and fibrocartilage injuries, especially in conjunction with precise ultrasound guidance or mini-open but not arthroscopic surgery. Muscles and bones are full of platelets (assuming an intact blood supply) and have not been shown to significantly benefit. PRP for discogenic pain is promising, with at least one Level I study showing good outcomes at 1 year and beyond.95 PRP for nerves and neuropathic pain remains investigational.
PRP procedures should ideally be performed by specialists capable of precisely identifying and guiding needles to sites of pathology using imaging guidance. Patients should avoid aspirin for 10 days and NSAIDS for 5 days. For optimum effect, PRP should not be in contact with local anesthetics and probably radiographic contrast dye. NSAIDS, which inhibit prostaglandin mediated vasodilation and have been shown to inhibit healing, should be avoided for at least 4-8 weeks following injections. While there is good evidence that PRP improves pain and function, there is limited evidence that it actually heals or regenerates tendons, discs or ligaments. Hopefully, future studies will continue to elucidate the healing and regenerative effects of PRP.
Acknowledgement: The authors would like to thank the non-profit 501(c)3 Napa Medical Research Foundation for their financial support.
Marko Bodor, MD, will deliver a Keynote speech discussing up-and-coming treatments of carpal tunnel syndrome at the 26th Annual Meeting of the American Medical Society for Sports Medicine on Thursday, May 11, in San Diego, CA.
Dr. Bodor has been a trailblazer in exploring innovative ways to treat carpal tunnel syndrome, one of the most common wrist and upper extremity conditions. He will explore this topic during his presentation titled, “Expanding the Treatment Options for Hand and Wrist Conditions.”
“Recent advances in high-frequency ultrasound allow the ‘camera’ to stay on the outside,” Dr. Bodor said. “The surgeon can see all the pertinent structures within the carpal tunnel, and the procedure can be done using a single 2-4 mm incision and local anesthesia. Most patients are able to return to work within a few days.”
Dr. Bodor is one of the pioneers of this technique, having performed over 100 operations. He works in Napa, California, and serves as the Director of Medical Research for the Napa Medical Research Foundation. He also is the Medical Director of the Wellness Center at the Queen of the Valley Medical Center in Napa. The founder of the Bodor Clinic, Regenerative Spine & Sports Medicine, Dr. Bodor is an assistant professor at University of California San Francisco and University of California Davis.
The presentation addresses a new approach to carpal tunnel release, the second-most common surgical procedure after hysterectomy. Dr. Bodor will cover the history of the procedure during the “Hot off the Press” Session.
We are delighted to announce Conrad Hewitt has joined the Napa Medical Research Board of Directors. Mr. Hewitt brings extensive board experience with him to the Foundation as well as a broad knowledge of the Napa community. It is our pleasure to welcome Con and his wife Linda to he NMRF family!
Conrad W. Hewitt
Mr. Hewitt received a B.S. degree in Finance from the University of Illinois and performed MBA post-graduate studies at the University of Southern California in addition to Executive Programs at Stanford Graduate School of Business, The Aspen Institute, and Kellogg School of Business.
After serving as a Captain in the U.S. Air Force at Strategic Air Command Headquarters, Mr. Hewitt joined Ernst & Ernst (Ernst & Young) where he specialized in financial institutions, hi-technology and health care industries for 33 years. Upon retirement, he became the Superintendent of Banks for the State of California and proceeded to found the Department of Financial Institutions. He later served as Chief Accountant of the U.S. Securities and Exchange Commission (SEC), Washington D.C., subsequently forming and leading the SEC Advisory Committee on Improvements to Financial Reporting.
Mr. Hewitt is a frequent speaker at industry and governmental conferences and has provided oral and written testimony to the U.S. Senate Finance Committee
He is currently director emeritus at Bank of the West, President of the Silverado Homeowner’s Association, and a member of the board of trustees for both Hawaii Pacific University and the Queen of the Valley Medical Center.
Recently published in “Techniques in Regional Anesthesia and Pain Management” by Elsevier
Regenerative medicine for muscle and ligament problems: Technical aspects and evidence
By Sean Colio, MD, Matthew McAuliffe, MD, Yvette Uribe, BA, and Marko Bodor, MD
Interest in regenerative medicine for treating musculoskeletal pathology has grown tremendously over the past decade. Part of its appeal lies in the ability to use a patient’s own cells to potentially heal acute and chronic injuries. While evidence grows supporting
its use in certain injuries, a perception exists that regenerative medicine may be a panacea. In this article,we review the evidence for platelet-rich plasma and bone marrow aspirate concentrate in treating muscle, ligament, and fibrocartilage injuries. We also offer our own practice experiences and technical considerations in the uses of these techniques.
PRP for muscle injuries
Muscle injuries can be classiﬁed as extrinsic due to external forces such as a laceration or direct blunt trauma to the muscle. Intrinsic muscle injuries are caused by muscular contraction during concurrent elongation resulting in over-extension of the ﬁbers and tearing. A common location for intrinsic muscle injuries is the weak point for the muscle unit at the myotendinous junction resulting in rupturing of muscle ﬁbers and small vessels causing bleeding and hematoma formation. The degree of muscle injury can be measured using the Peetrons ultrasonography classiﬁcation: grade 0 has no visible lesion on ultrasound, grade I corresponds to minimal elongation with less than 5% of muscle involved, grade II involves partial tears involving 5%-50% of muscle volume or cross-sectional diameter and grade III lesions are full-thickness muscle tears with complete retraction.
Traditional treatment options have been directed toward reducing bleeding and swelling at the injury including rest, compression, elevation, physical therapy, ice, nonsteroidal anti-inﬂammatory drugs, ultrasound modalities, and time. Newer treatment options aiming to accelerate the rate of recovery, reduce recurrent injuries and minimize ﬁbrosis are the subject of ongoing research and have led to an interest in the use of platelet-rich plasma (PRP). PRP injected at the site of muscle injury has been thought to modulate inﬂammation, improve angiogenesis, reduce ﬁbrosis, and enhance muscle ﬁber regeneration.4-6 PRP might replace a muscle hematoma with platelets, plasma, and a ﬁbrin scaffold to enhance hemo-stasis, secrete growth factors and guide the repair process.
Wright-Carpenter et al induced gastrocnemius muscle injuries in mice and injected autologous conditioned plasma vs saline. At 30-48 hours histological results showed accel-erated muscle satellite cell activation and increased diameter of regenerating myoﬁbers in the PRP group vs the saline group. Quarteiro et al induced muscle injuries in the gastro-cnemius muscle of rats comparing PRP to physiologic serum injection to no treatment. Between 7 and 21 days, the PRP group showed a higher mean quantity of collagen production, but after 21 days the morphological features of muscles were the similar in all groups. Delos et al induced gastrocnemius muscle injuries in rats comparing injections of PRP vs saline. There were no differences between groups at any time point for the primary outcome measure of maximal isometric torque, nor were there any differences in the proportion of centronucleated muscle ﬁbers and scar tissue on histological analysis after 15 days.
Hamstring muscle injuries are one of the most common injuries among athletes resulting in substantial time lost from sport. PRP has been used for these injuries with the goal of faster return to training and competition and reduced chance of reinjury. PRP is typically injected in the acute phase, 24-48 hours postinjury. Rettig et al performed a retrospective review of 10 NFL players with similar hamstring injuries, 5 of whom received PRP 24-48 hours postinjury and 5 of whom did not. The median time for return to play was 20 days in the PRP group and 17 days in the non-PRP group. A recent study by Zanon et al11 evaluated 25 professional soccer players with grade 2 hamstring injuries, all of whom received PRP injections. The average return to sport was 36.8 days, signiﬁcantly longer than the 22 days reported by Ekstrand for grade 2 hamstring injuries treated without PRP.
In a double blind randomized controlled trial of PRP vs saline for acute muscle injuries in a cohort of 80 competitive and recreational athletes, Reurink et al found that PRP did not accelerate return to play or lower the reinjury rate at 1 year. Hamilton et al compared PRP vs no injection for acute grade 1 or 2 hamstring injuries among a population of professional, semiprofessional, and amateur athletes in Qatar. The median time for return to sport was 21 days in the PRP group and 25 days among those receiving no injection. Guillodo et al15 did not ﬁnd faster return to play for severe (grade 3) hamstring injuries treated with a single PRP injection.
Some studies did show PRP as helping athletes return to sports more quickly. Hamid et al provided a single PRP injection of 3 mL in 14 patients with acute grade 2 hamstring injuries.16 No local anesthetic was used, the PRP was not activated, and the patients were kept supine for 10-15 minutes. The mean return to play time was 26.7 +/- 7 days in the PRP group and 42.5 +/- 20.6 days in the control group. Recently, Rossi et al17 published results on a single PRP injection for grade 2 gastrocnemius, hamstrings, and quad-riceps muscle injuries. They reported a return to play of 21.1 +/- 3.1 days for the PRP group and 25 +/- 2.8 days for the control group. No local anesthetic was used, the PRP was not activated, and the amount of PRP was correlated with the volume of the injury.
While the safety proﬁle for PRP is appealing, based on the current evidence it is difﬁcult to recommend its use in muscle injuries as a means for faster recovery. This should not be surprising because muscle is highly vascularized and has abundant platelets, in contrast to tendons, ligaments, and intervertebral discs. As such the administration of additional platelets would not appear to be helpful except in the case of infarcted or ischemic tissue.
Mesenchymal stem cells for muscle injuries
Hernigou et al18 published on the use of bone marrow aspirate concentrate (BMAC) in conjunction with arthroscopic rotator cuff repair in 59 patients. At time of follow-up 10 years later, 40 of the 59 did not have evidence of a re-tear or progression of fatty inﬁltration on magnetic resonance imag-ing (MRI), whereas the remaining 19 had an increase of 1 grade of fatty inﬁltration. Hernigou et al suggested that injection of BMAC into atrophied muscle may have had a positive effect, however, it is not possible to tell whether the noted improvements were attributable to a direct effect of BMAC on muscle or an indirect effect related to improved muscle activation following tendon healing or both. BMAC is being researched to treat chronic limb ischemia and infarcted myocardium. Tateishi-Yuyama et al injected BMAC into the gastrocnemius of ischemic limbs and demonstrated angio-genesis and the formation of stable capillary vessels. Beeres et al showed that BMAC injection into infarcted myocar-dium improved MRI and tissue Doppler imaging parameters of diastolic function.
PRP for ligament and ﬁbrocartilage injuries
Ligament injuries have traditionally been classiﬁed as grades 1-3. A grade 1 injury is stretching of the ligament with no visible tear, grade 2 is an incomplete tear or rupture and grade 3 is complete tear or rupture of the ligament. The mechanism of injury involves joint distraction and tensile strain in the direction that the ligament is stabilizing.
PRP has been shown to enhance anabolic effects such as collagen synthesis, angiogenesis, proliferation of ﬁbroblasts and anti-ﬁbrotic effects. PRP has been shown to augment the differentiation of musculoskeletal stem cells into mature cells. In-vivo studies have assessed the effects of PRP on repair of anterior cruciate ligament (ACL) injuries, acute medial collateral ligament (MCL) injuries, meniscal tears, high ankle sprains, and ulnar collateral ligament (UCL) injuries.
Murray et al have done extensive research showing that PRP combined with a collagen composite improves the heal-ing of ACL grafts in pigs. When used for primary repair of the ACL, they found only an 11% increase in ligament strength compared to controls. They also found that high concentrations of PRP (5) were inhibitory on proliferation of ACL ligament cells in vitro compared to low concentrations (1). In humans, Orrego et al noted that PRP had an enhancing effect on the graft maturation process evaluated by MRI signal intensity, but no signiﬁcant effect on the osteoligamentous interface or tunnel widening at 6 months. Sanchez et al32 noted higher synovial coverage and graft width in patients treated with PRP as assessed arthroscopically 6-24 months following ACL reconstruction. Other studies have shown the beneﬁts of PRP with improved graft maturation and vascularization in ACL reconstruction using autologous tendon grafts.
In a series of 19 professional soccer players with subacute partial ACL disruptions, Seijas et al injected PRP into the torn bundle during and most signiﬁcantly after arthroscopy when all the irrigation ﬂuid had been drained. All players experienced restoration of knee stability as assessed objectively by KT-1000 measurements, with 16 returning to pre-injury levels of sport at an average of 16 weeks following the procedure, 2 to lower levels of sport, and 1, who had experienced cartilage damage, not being able to return to sport.35
MCL tears generally have a good prognosis with conservative treatment with or without PRP. Foster et al noted a 27%faster return to play among those who received PRP into the MCL within 72 hours of injury. Yoshioka et al studied PRP for MCL injuries in 31 rabbits, showing higher levels of growth factors and earlier signs of repair at 3 and 6 weeks after administration.
Injuries of the UCL of the elbow can devastate the career of a throwing athlete and usually necessitate reconstructive surgery. In 34 athletes with partial UCL tears who had failed 2 months of conservative therapy, Podesta et al performed ultrasound-guided PRP injections resulting in an average return to play time of 12 weeks and 88% of patients playing without pain at 70 weeks. A recent case report by Hoffman et al demonstrated a good outcome with return to activity without pain for a patient who underwent UCL reconstruc-tion augmented by PRP and a dermal allograft.
The meniscus of the knee functions to reduce contact pressure between the femoral condyle and the tibial plateau. When the meniscus is injured, it increases the risk of osteoarthritis. Urzen and Fullerton reported on a case of a 43-year-old athlete with a displaced bucket-handle tear of his medial meniscus, which was reduced with manipulation and completely healed, as assessed by arthroscopy, following a series of 3 PRP injec-tions. The authors acknowledged that there have been several case reports documenting spontaneous healing of bucket-handle medial meniscus tears without PRP.
PRP has been studied in conjunction with arthroscopic surgery for meniscus and hip labral tears, showing no beneﬁt. Recognizing that irrigation ﬂuid during arthroscopic surgery might dilute or inhibit PRP, Pujol et al used a mini-open approach to repair the meniscus with and without the addition of PRP in a case-control study. Both groups improved signiﬁcantly, but the PRP group had slightly better pain, activity and quality of life scores, and 75% had resolution of increased T2 signal in the outer meniscus compared to 40% of controls at 1 year.
Injuries to the syndesmosis between the tibia and the ﬁbula (high ankle sprains) are uncommon but can be very debilitating with a high likelihood of long-term disability. In these cases, the anterior inferior tibio-ﬁbular ligament is often partially or completely ruptured. Using ultrasound, Laver et al diagnosed and injected PRP in 8 patients with anterior inferior tibio-ﬁbular ligament injuries and compared them to 8 controls treated without PRP. They noted a more rapid return to play, less pain and better resolution of the gap between the tibia and ﬁbula in the PRP compared with the control group.
Mesenchymal stem cells for ligament and ﬁbrocartilage injuries
Kenaya et al studied partial ACL tears in rats and noted improved healing and mechanics in animals injected with cultured bone marrow mesenchymal stem cells compared with controls. Oe et al created partial ACL tears in rats and injected BMAC, cultured bone marrow mesenchymal stem cells and buffered saline. At 4 weeks the BMAC and cultured cell groups recovered 90% and 88% tensile strength compared with 50% among controls. Centeno et al used a ﬂuoroscopi-cally guided technique to inject 10 patients with acute and subacute partial and less than 1 cm retracted complete ACL tears using a combination of BMAC, PRP, and platelet lysate. At 3 or more months, 7 of 10 patients experienced improvement of pain, function and ACL appearance on MRI. Centeno et al reported on a case of a 34-year old who experienced a 23% increase in meniscal volume 3 months following treatment with cultured bone marrow mesenchymal cells. Vangness et al compared injections of 150 (106 vs 50) 106 allogeneic cultured bone marrow mesenchymal cells 7-10 days after meniscectomy and found that 24% of the higher vs 6% of the lower vs 0% of the sodium hyaluronate groups had increased meniscal volume at 1 year. Note that typical quantities of noncultured mesenchymal cells harvested from bone or fat are several orders of magnitude smaller than cultured cells.
In our 10 years of experience using precise ultrasound guidance to inject PRP, our highest success rates have been in treating injuries that can be visualized on ultrasound, such as intra-substance, partial or small full-thickness tears in ligaments and tendons. We have noted that the conﬁguration of tendons or ligaments makes a difference in outcome. Flat tendons and ligaments with broad attachment areas, such as the common extensor tendon of the forearm and the MCL of the knee, tend to heal better than round tendons with short attachment areas, such as the common ﬂexor tendon of the forearm.
Speciﬁc considerations when injecting biologic agents into tendons or ligaments includes being aware that tendons and ligaments are solid or semi-solid structures and that the spread of injectate should be seen in 3-dimensions to ensure that it reaches all areas of pathology. This requires skill and hand to eye coordination in order to precisely and efﬁciently rotate the ultrasound transducer back and forth between short and long axis views around a point of interest. Additional technical considerations include calculating the volume of a torn area or region of pathology before injecting and knowing when to activate PRP. Too much volume could lengthen and widen a tear while too many cells could inhibit healing. The volume of a tear or region of pathology in milliliters is calculated by multiplying its width, depth, and length in centimeters. Calcium chloride 10% should be used to activate PRP (in a 1:6 ratio) when injecting ligaments that are exposed to joint ﬂuid in order to enable platelet adhesion and aggregation. Joint ﬂuid contains plasmin, which inhibits platelet aggregation. Local anesthetics inhibit platelet aggre-gation and should not be mixed with PRP or BMAC.
In our experience, the success of treatment depends on the physician/surgeon having high level diagnostic ultrasound skills, enabling the discovery of problems that might have been missed resulting in a diagnosis of “chronic pain.” Furthermore, a number of ultrasound interventional techni-ques require high level ultrasound visualization skills to perform successfully, such as those recently developed for injecting the ACL and PCL.50,51 We recommend that all physicians who wish to practice regenerative medicine become proﬁcient in diagnostic and interventional ultra-sound, as covered in several excellent texts.
Most of the published evidence, including one level I study, indicates that PRP and BMAC are not effective for acute muscle injuries. There is good evidence, including one level I study, that BMAC is effective in improving pain, function and perfusion in ischemic muscle. There is level II evidence indicating PRP and BMAC to be effective for some ligament and ﬁbrocartilage injuries when done separate from arthro-scopic surgical procedures. Current best practice is for PRP and BMAC to be injected precisely to areas of identiﬁed pathology using ultrasound or other imaging guidance.
Greetings from the Research Lab!
We would like to share the latest news from the field, recent findings from our clinical studies, and stories about the people of Napa Medical Research Foundation.
November 2016 Newsletter
WELCOME TIM HERMAN
We are delighted to announce long-time Napa resident Tim Herman has joined the NMRF Board of Directors. Tim brings many years of experience with non-profit organizations to the Foundation, along with a deep commitment to the power of philanthropy.
Our local community recognizes Tim for his significant contributions to the Queen of the Valley Medical Center both as a dedicated Board member for many years and through the establishment of the Peggy Herman Neuroscience Center and the Herman Family Pavilion. He is the founder of the International Children’s Dream Foundation, committed to providing vital resources to young people trying to manage life’s challenges, such as violence and substance abuse.
Tim has served on multiple local school boards and is very engaged with promoting health and well being across the county. His wealth of knowledge and immense generosity of spirit will greatly benefit the Foundation and we are delighted to have his experience and wise counsel to strengthen our Board.
LATEST INNOVATIONS FOR TREATING DISC DEGENERATION
Chronic back pain is considered the number one cause of musculoskeletal disability worldwide. As the fifth most common reason for a physician visit, it affects five out of ten working adults and is responsible for causing 40% of missed days off work. Unfortunately, most individuals will experience acute back pain at some point in their lives.
The most common cause of back pain among younger and middle aged adults is related to tears of the collagen fibers in the disc. These tears by themselves can cause pain, or if a significant number of fibers tear, the disc can bulge and herniate. Bulges and herniation can be a source of irritation or can compress spinal nerves causing “sciatica”. Over time, if the disc does not repair its’ self, it deteriorates and leads to spinal stenosis, or narrowing of the spaces around the spinal nerves and causing pain in the arms or legs.
Up until recently, for patients with injured discs and chronic pain, the only options were to wait and hope the disc heals itself and if not, then treat the symptoms. Recently in sports medicine it was discovered that platelets obtained from the blood and other cells in the bone marrow can be used to repair chronically torn non-healing ligaments and tendons. Dr. Bodor was among the first to utilize these in the Bay Area and, given that he is also an expert on treating the spine, was among the first to use this technique for disc pain. Dr. Bodor described the rationale for the technique and pilot series of patients in a chapter in the textbook, Platelet Rich Plasma (PRP), editor Lana, publisher Springer, 2014 (available on Amazon.com). Dr. Greg Lutz, at the Hospital for Special Surgery in New York City, published positive results for PRP for disc pain in a randomized blinded placebo-controlled trial in the journal PMR in January 2016.
Owing to the relatively low available blood supply in the disc, the introduction of concentrated platelets can seal tears and contribute vital growth and healing factors to facilitate natural repair processes. Dr. Bodor has administered PRP therapy to discs experiencing some degree of degeneration in the lumbar, thoracic and cervical spine. With the support of the Napa Medical Research Foundation, he and Research Assistant Yvette Uribe are carefully monitoring the progress of more than 170 patients to prove the effectiveness of the PRP as a healing agent. The findings thus far yield a minimum 75% improvement rate.
Of special interest is the new technique Dr. Bodor developed during the course of the study. Whenever needles are placed into the neck, a high degree of skill and vigilance is necessary to ensure safety and comfort in doing the procedure. Traditionally such injection procedures are done using x-rays only, but Dr. Bodor developed a technique combining ultrasound and x-rays which allows for better visualization of the carotid arteries, brachial plexus and other vulnerable structures and ensure precise placement into the discs or the cervical facet joints.
Dr. Bodor and his research team were asked recently to write a review article on the evidence for PRP and stem cells in treating chronic painful muscle and ligament injuries. Their work is currently going into publication in Techniques in Regional Anesthesia and Pain Medicine, a peer-reviewed journal published by Elsevier.
As a strong advocate for the work of Dr. Bodor and as a contributor to the Napa Medical Research Foundation, could you please tell us how you got to know Dr. Bodor and your personal experience in receiving these leading edge treatments?
To begin, it is important to recognize that Dr Bodor is an extraordinary, superior and bright individual in addition to being a highly skilled and talented physician. He has remarkable breadth of knowledge well beyond the medical arena. This enhances his ability to examine problems with fresh and unique insight and creates a very engaging experience for the patient.
My own experience with Dr. Bodor comprises two separate medical conditions on two different parts of my body: the treatment I received for both – Platelet Rich Plasma – proved highly effective.
Nearly 20 years ago, I tore my gluteus medius tendon off the end of my femur which required a highly specialized and uncommon surgery at the time. While the team at Mayo Clinic reattached the tendon, it never fully healed. I was left with a misaligned foot that left me without the ability to run and a pronounced limp when walking. Sixteen years later I was referred to Dr. Bodor to see if I could possibly benefit from the use of platelets where the tendon had pulled away from the bone. Following the ultrasound-guided PRP injections, the limp has significantly healed and my walking has improved immensely!
Recognizing the powerful impact of the platelets, I engaged Dr. Bodor in a discussion about the severe arthritis in my right hand. After accompanying me personally to the hand specialized surgeon in San Francisco, and lending his exceptional technical ability to observe tendons, nerve and bone, the partially-successful surgery still resulted in an an incredible amount of chronic pain. With several platelet injections, Dr. Bodor has been able to greatly reduce that pain, and improve my functionality.
~ Christopher Peacock
We would like to thank Chris Peacock for sharing his story with us. His generous support for the Napa Medical Research Foundation and his advocacy for Dr. Bodor’s work is greatly appreciated!
STEM CELL TREATMENTS: Who Can be Trusted?
In June of this year, The Sacramento Bee published an article, “Growing industry or unregulated risk?,” investigating the operations of stem cell centers offering low-risk alternative treatments whose procedures have not been fully tested and regulated by the Food and Drug Administration (FDA). The authors found 570 clinics operating in the US who are providing some form of stem cell treatment.
One company in particular, Nervana, captured the attention of Dr. Bodor with their claim of being able to cure neuropathy with the injection of third party umbilical cord stem cells. As you will soon read in the Napa Valley Register in a Letter to the Editor authored by Dr. Bodor, there are clearly some unethical and illegal practices in effect here.
For the researchers around the country making vital new discoveries and insights into the harvesting and application of stem cells in legal and fully FDA-sanctioned labs, these clinics are the “snake oil charmers” of the 1800s and have the potential to seriously damage the invaluable work being done in this field.
The Napa Medical Research Foundation is here to support the legal, valid work of Dr. Bodor, and his colleagues at Mayo Clinic, Stanford and UCSF, in their efforts to make truly ground-breaking advances in the treatment of a wide variety of diseases and conditions.
We believe it is essential that the public be informed: For example, using umbilical cord stem cells obtained from a third party is illegal. While not yet regulated, procedures that utilize the patient’s own stem cells for reintroduction into their body are acceptable, though currently under consideration for regulatory oversight
It is important that stem cell-related treatments find precedent in medical literature, be used in conjunction with an Independent Review Board (IRB) approved clinical study, and be performed in a legal, FDA approved lab.
The field of regenerative medicine holds a great deal of promise from treating the orthopedic and musculoskeletal conditions to breakthroughs in diabetes treatment, improving heart failure outcomes and treating traumatic brain injuries. It is imperative we maintain the necessary level of ethical and legal behavior in our clinical studies, in the development of new treatments, and in the promises made to patients suffering and in pain worldwide.
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