PRP and Major League Baseball

A major league baseball pitcher begins throwing again after Platelet Rich Plasma.

Read the full story. AM (Total Tendon)

Future Trends in Sports Medicine

Below is the abstract from a soon to be published article discussing the use of PRP for tendon and muscle. It will be published in a volume of Clinics in Sports Medicine entitled: "Future Trends in Sports Medicine"

AM (Total Tendon, ApexPRP)

Treatment of Tendon and Muscle Using Platelet-Rich Plasma.Mishra A, Woodall J Jr, Vieira A.Clin Sports Med. 2009 Jan;28(1):113-125.Department of Orthopedic Surgery, Menlo Medical Clinic, Stanford University Medical Center, 1300 Crane Street, Menlo Park, CA 94025, USA.

Tendon and muscle injuries are common in elite and weekend athletes. Treatment of these injuries in both groups is rapidly evolving. Sports medicine patients are demanding better and less invasive solutions for all types of musculoskeletal disorders. In this context, platelet-rich plasma (PRP) has emerged as a potential solution. PRP is a fraction of whole blood containing concentrated growth factors and proteins. These cytokines direct tissue healing through autocrine and paracrine effects. The number of basic science, animal, and human investigations of PRP for tendon and muscle injuries worldwide has risen sharply in recent years. These studies are helping clinicians better understand the mechanisms of PRP and are guiding novel treatment protocols. In this paper, the value of PRP as a treatment for acute or chronic tendon and muscle disorders is explored.

Platelet Rich Plasma helps Treat Achilles Tendons

The published and presented data supporting the use of buffered platelet rich plasma continues to grow. PRP has now been shown in a small study to help treat chronic achilles tendonitis (tendinosis).

AM (Total Tendon, ApexPRP)

Guelfi et al recently presented a series of 16 cases of non-insertional achilles tendonitis at a recent meeting in Brazil. They used unactivated, buffered platelet rich plasma prepared using the Biomet Recover System, also known as the GPS. Significant improvement was found in all 16 of their patients via imaging. They also reported the patients returning to sports at six months with a high degree of satisfaction.

MRI Prior to PRP

4 months after PRP

"International Federation of Foot and Ankle Societies", , Third Triennial Scientific Meeting, Costa do Sauipe, Bahia, Brazil September 18-20, 2008. (The case shown is from AM)

Growth Factors in Shoulder Surgery

In the article outlined below, Dr. Randelli and his colleagues have confirmed that valuable growth factors are released when performing an arthroscopic acromioplasty. This is a landmark paper that will be cited many times as we try to understand how to use platelet rich plasma and other biologic treatments. His work for the first time has confirmed that the mechanical removal of an acromial spur has biologic consequences. Excellent information.

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Knee Surg Sports Traumatol Arthrosc. 2008 Oct 31.

Release of growth factors after arthroscopic acromioplasty.

Randelli P, Margheritini F, Cabitza P, Dogliotti G, Corsi MM.

It has recently been postulated that a variety of growth factors may be released from cancellous bone after an acromioplasty. The aim of this study was to demonstrate the presence of growth factors in the subacromial space after acromioplasty. Between October 2006 and March 2007, 23 patients underwent arthroscopic acromioplasty. A sample of at least 3 ml of fluid from the shoulder was obtained 15 min after the end of the procedure. At the same time another sample of 3 ml of the patient's venous blood was obtained as a control. The concentrations of growth factors in the fluids collected were determined using enzyme-linked immunosorbent assay (ELISA). The growth factors assayed were platelet-derived growth factor-AB (PDGF-AB), basic fibroblast growth factor basic (bFGF) and transforming growth factor beta 1 (TGF-beta1). The concentrations of TGF-beta1 (p = 0.0001), PDGF-AB (p = 0.02), and bFGF (p <>

PRP promotes Cell Proliferation

Below is still more basic science evidence to suggest platelet rich plasma is helpful for wound healing and tissue engineering.

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Plast Reconstr Surg. 2008 Nov;122(5):1352-60.

Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts.

Kakudo N, Minakata T, Mitsui T, Kushida S, Notodihardjo FZ, Kusumoto K.

Department of Plastic and Reconstructive Surgery, Kansai Medical University, Osaka, Japan. kakudon@takii.kmu.ac.jp

BACKGROUND: This study evaluated changes in platelet-derived growth factor (PDGF)-AB and transforming growth factor (TGF)-beta1 release from platelets by platelet-rich plasma activation, and the proliferation potential of activated platelet-rich plasma and platelet-poor plasma on human adipose-derived stem cells and human dermal fibroblasts. METHODS: Platelet-rich plasma was prepared using a double-spin method, with the number of platelets counted in each preparation stage. Platelet-rich and platelet-poor plasma were activated with autologous thrombin and calcium chloride, and levels of platelet-released PDGF-AB and TGF-beta1 were determined by enzyme-linked immunosorbent assay. Cells were cultured for 1, 4, or 7 days in serum-free Dulbecco's Modified Eagle Medium supplemented with 5% whole blood plasma, nonactivated platelet-rich plasma, nonactivated platelet-poor plasma, activated platelet-rich plasma, or activated platelet-poor plasma. In parallel, these cells were cultured for 1, 4, or 7 days in serum-free Dulbecco's Modified Eagle Medium supplemented with 1%, 5%, 10%, or 20% activated platelet-rich plasma. The cultured human adipose-derived stem cells and human dermal fibroblasts were assayed for proliferation. RESULTS: Platelet-rich plasma contained approximately 7.9 times as many platelets as whole blood, and its activation was associated with the release of large amounts of PDGF-AB and TGF-beta1. Adding activated platelet-rich or platelet-poor plasma significantly promoted the proliferation of human adipose-derived stem cells and human dermal fibroblasts. Adding 5% activated platelet-rich plasma to the medium maximally promoted cell proliferation, but activated platelet-rich plasma at 20% did not promote it. CONCLUSIONS: Platelet-rich plasma can enhance the proliferation of human adipose-derived stem cells and human dermal fibroblasts. These results support clinical platelet-rich plasma application for cell-based, soft-tissue engineering and wound healing.

Best Treatment for Tennis Elbow?

We are polling people to figure out the best treatment for a patient with 3 months of tennis elbow pain (lateral epicondylitis). The patient is a healthy 42 year old female who plays 2-3 hours per week and can no longer participate. Her pain now occurs even with activities of daily living such as driving. Please vote in the poll on this blog.

Comment as you wish as well.

AM (Total Tendon)

Cartilage Formation better with Platelet Rich Plasma

Here is more evidence that PRP may be helpful for cartilage regeneration.

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Platelet lysate favours in vitro expansion of human bone marrow stromal cells for bone and cartilage engineering.

Zaky SH, Ottonello A, Strada P, Cancedda R, Mastrogiacomo M.

Istituto Nazionale per la Ricerca sul Cancro, and Dipartimento di Oncologia, Biologia e Genetica dell'Universita' di Genova, Genova, Italy.

The heterogeneous population of non-haematopoietic cells residing in the bone marrow (bone marrow stromal cells, BMSCs) and the different fractions and components obtained from platelet-rich plasma provide an invaluable source of autologous cells and growth factors for bone and other connective tissue reconstruction. In this study, we investigated the effect of an allogenic platelet lysate on human BMSCs proliferation and differentiation. Cell proliferation and number of performed cell doublings were enhanced in cultures supplemented with the platelet-derived growth factors (platelet lysate, PL), either with or without the concomitant addition of fetal bovine serum (FBS), compared to cultures performed in the presence of FBS and FGF2. Both in vitro and in vivo osteogenic differentiation were unaltered in cells maintained in medium supplemented with PL and not FBS (Only PL) and in cells maintained in medium containing FBS and FGF2. Interestingly, the in vitro cartilage formation was more effective in the pellet of BMSCs expanded in the Only PL medium. In particular, a chondrogenic differentiation was observed in pellets of some in vitro-expanded BMSCs in the Only PL medium, whereas pellets from parallel cell cultures in medium containing FBS did not respond to the chondrogenic induction. We conclude that the platelet lysate from human source is an effective and even more beneficial substitute for fetal bovine serum to support the in vitro expansion of human BMSCs for subsequent tissue-engineering applications.

Stanford Football Player returns after PRP

A Stanford football player who had chronic severe patellar tendonitis has returned to play this year after being treated with platelet rich plasma by Dr. Mishra.
Click here to read the full story.

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United Nations and Platelet Rich Plasma

AM at the United Nations

This week Dr. Allan Mishra presented his platelet rich plasma research at the United Nations in Geneva, Switzerland. The lecture was part of a worldwide conference on stem cells and regenerative medicine. Researchers, clinicians and government ministers from the United States, Dubai, Japan, Sinapore, Australia, Italy, France, Switzerland, the Netherlands, Spain, England, Turkey, Brazil and even Kazakhstan were in attendance.

The BioBridge meeting included the researchers from Kyoto Japan who are pioneering the use of induced pluripotential stem cells (an alternative to embryonic stem cells) and several physicians using platelet rich plasma (PRP) for dermatologic, traumatic and degenerative conditions. Data from the meeting suggests PRP is ahead of stem cells as a therapeutic biologic agent in terms of applications and safety.

The meeting was a collaborative and inspiring international event. The relationships established and the sharing of data will hopefully lead to future multi-disciplinary discoveries.

AM

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Forbes Magazine Article Platelet Rich Plasma Tennis

Forbes just published an article on the use of platelet rich plasma (PRP) in elite athletes. It discusses the value of PRP in the context of cortisone and surgery. Forbes Story

To join in a group of patients and providers discussing the use of PRP and other treatments for tendon related injuries join the FREE Total Tendon Network.

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Wired Magazine Stem Cells and PRP

Wired magazine just ran an article about stems and platelet rich plasma. Dr. Mishra's work is mentioned toward the end of the article.

Wired Stem Cell and PRP Article

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San Francisco Chronicle Article: "Miracle Cure"

The San Francisco Chronicle calls platelet rich plasma a "Miracle Cure". To read the full story, click here.

Join the FREE Total Tendon Network to interact with patients and providers familar with platelet rich plasma as a treatment.

For more information:

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Pioneer PRP Story on ABC TV

ABC TV in San Francisco just aired a story about the pioneering of platelet rich plasma for tendon related problems such as tennis elbow or patellar tendonitis.

Link to ABC TV Story about Stanford Football Player

To learn more about PRP visit: ApexPRP

Join the Total Tendon Network to have the most up to date information and interact with other patients and providers.

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How PRP works for Tendonitis and Tendon Tears

Platelet Rich Plasma produced by AM at Total Tendon

Platelet rich plasma (PRP) continues its advance as a novel and increasingly valuable treatment for tendon related problems like chronic tendonitis (also medically known as tendinosis). It is important to realize that not all physicians and machines produce clinically valuable (meaning it helps improve your pain and function) PRP. Published peered reviewed data suggests that PRP should contain at least 5 times the number of whole blood platelets.

(See Dr. Mishra's study published in American Journal of Sports Medicine Nov. 2006 for details)


As PRP evolves, it is important to find physicians and surgeons who base their clinical decisions on the literature not on opinion. Also, they should use devices that produce PRP with the appropriate concentrations of platelets. Not all methods are the same.

PRP Website: ApexPRP.com

Platelet rich plasma has been found to work via three mechanisms:

1. Release of Growth Factors increase local cell division (producing more cells)

2. Inhibition of excess inflammation (decreased early macrophage proliferation)

3. Recruitment of circulating or bone marrow derived cells that help repair tissue.

This combination of mechanisms helps heal a tendon. Animal data confirm that PRP helps produce a biomechanically stronger tendon.

All of these statements are based on peer reviewed publications.


AM

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Platelet Rich Plasma and Rotator Cuff Repair

We now have published evidence that PRP is safe and may be useful in arthroscopic rotator cuff repair. This excellent study by Dr. Randelli and his colleagues will lead the way to larger trials.

Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study.

Here is Dr. Randelli's excellent rotator cuff video. (Thanks for sharing it.)

Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N.

Dipartimento di Scienze Medico-Chirurgiche, Policlinico San Donato, Universita degli Studi di Milano, Milano.

Background and purpose. Arthroscopic repair of rotator cuff tears can produce excellent results. The application of platelet rich plasma during arthroscopic rotator cuff repair is safe, and produces results which do not deteriorate over time. Methods. A total of 14 patients undergoing arthroscopic repair of a rotator cuff tear received an intra-operative application of autologous platelet rich plasma in combination with an autologous thrombin component after tear repair. Following the procedure, patients were given a standardized rehabilitation protocol, and followed for 24 months. Outcome measures included a pain score (VAS) as well as functional scoring (UCLA and Constant scores). Results. Of the original 14 patients, 13 were seen at a final follow-up appointment 24 months after the index operation. Patients demonstrated a significant decrease in VAS scores and significant increases in the UCLA and Constant scores at 6, 12 and 24-month follow-ups compared to a pre-operative score. Conclusion. No adverse events related to this application were noted during the procedure. The application of platelet rich plasma during arthroscopic rotator cuff repair is safe and effective, and produces results which seem to be stable with time. A prospective randomized investigation will be necessary to ascertain the efficacy of platelet rich plasma application to improve or expedite the surgical outcome following arthroscopic rotator cuff repair.

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Platelet Rich Plasma beats Cortisone

Gosens and Sluimer in a prospective, randomized controlled trial of 100 patients with tennis elbow found PRP beat cortisone in terms of improvement in pain and function at 24 weeks. This excellent study (Level 1 evidence) for the first time confirms platelet rich plasma performs better than the "gold standard" of treatment for patients with tennis elbow that don't respond to simple treatments.

Gosen and his colleagues will be hosting a "Trends in Tendinopathy" course next week in Europe. AM will be presenting and in this space, I will report the details of that important conference.

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Platelet Rich Plasma Treats Stanford Football Player

A San Francisco based TV station just aired a segment on the use of platelet rich plasma to treat a Stanford football player. Here is a link to the spot.

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PRP Used in Chronic Knee Tendonitis

Dr. Mishra's method of using platelet rich plasma to treat chronic knee tendonitis was discussed in a recent story about a college football Player. Here is a link to the story.

Please also visit our new website: Tendon Tips to view a story about Tiger Woods' recent knee surgery

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Platelet Rich Plasma on TV in Los Angeles

A TV story on ABC7 in Los Angeles California just aired. The story discusses the value of using platelet rich plasma for chronic tennis elbow. It follows a patient who is an avid tennis player who was able to return to her game with a single PRP injection.

Link to TV Story

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Platelet Rich Plasma Basic Science

This is a video produced by Dr. Allan Mishra discussing the basic science of PRP. Future videos will discuss cell culture, animal and human studies. For more information, please visit either Total Tendon or ApexPRP.

More Evidence that PRP may heal Tendons

In this study the authors found that PRP releasate stimulated cell proliferation and total collagen production. It is an interesting article that adds to the growing body of PRP knowledge.

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Can Platelet-Rich Plasma Enhance Tendon Repair? A Cell Culture Study.

de Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA, van Osch GJ.

BACKGROUND: Autologous platelet-rich plasma (PRP) application appears to improve tendon healing in traumatic tendon injuries, but basic knowledge of how PRP promotes tendon repair is needed. HYPOTHESIS: Platelet-rich plasma has a positive effect on cell proliferation and collagen production and induces the production of matrix-degrading enzymes and endogenous growth factors by human tenocytes. STUDY DESIGN: Controlled laboratory study. METHODS: Human tenocytes were cultured 14 days in 2% fetal calf serum medium complemented with 0%, 10%, or 20% vol/vol platelet-rich clot releasate ([PRCR] the active releasate of PRP) or platelet-poor clot releasate (PPCR). At day 4, 7, and 14, cell amount, total collagen, and gene expression of collagen Ialpha1 (COL1) and IIIalpha1 (COL3), matrix metalloproteinases ([MMPs] MMP1, MMP3, and MMP13), vascular endothelial-derived growth factor (VEGF)-A, and transforming growth factor (TGF)-beta1 were analyzed. RESULTS: Platelet numbers in PRP increased to 2.55 times baseline. Growth-factor concentrations of VEGF and platelet-derived growth factor (PDGF)-BB were higher in PRCR than PPCR. Both PRCR and PPCR increased cell number and total collagen, whereas they decreased gene expression of COL1 and COL3 without affecting the COL3/COL1 ratio. PRCR, but not PPCR, showed upregulation of MMP1 and MMP3 expression. Matrix metalloproteinase 13 expression was not altered by either treatment. PRCR increased VEGF-A expression at all time points and TGF-beta1 expression at day 4. CONCLUSION: In human tenocyte cultures, PRCR, but also PPCR, stimulates cell proliferation and total collagen production. PRCR, but not PPCR, slightly increases the expression of matrix-degrading enzymes and endogenous growth factors. CLINICAL RELEVANCE: In vivo use of PRP, but also of PPP to a certain extent, in tendon injuries might accelerate the catabolic demarcation of traumatically injured tendon matrices and promote angiogenesis and formation of a fibrovascular callus. Whether this will also be beneficial for degenerative tendinopathies remains to be elucidated. Am J Sports Med. 2008 Mar 7

Platelet Rich Plasma Wins!

In our informal survey of best names, "Platelet Rich Plasma" won with 61% of the vote with "PRP" taking 22%, "Platelet Gel" 8% and "Platelet Enriched Plasma and Growth Factors" 4% each. With a total of 83% of the votes, Platelet Rich Plasma/PRP wins in a landslide.

I propose we end the argument of what to name it and begin to define it in studies moving forward. The landscape of PRP is scattered at best. In order to figure out how best to use this important tool, we must agree on what we are talking about. Please see the post below for a definition that is published in the literature.

I am repeating the survey of what machine producing the best PRP. I'll post the results in a month.

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What is platelet rich plasma (PRP)?

Marx one of the pioneers of PRP defined it quite simply: "it is a volume of autologous plasma that has a platelet concentration above baseline". (Marx, Implant Dentistry Dec. 2001, pp. 225-228) There have been other attempts to specific what define PRP but I think this one is the best.

I would add that PRP naturally is unactivated. In his paper, Dr. Marx states that activation of platelet results 70% of the stored growth factors being secreted with in 10 minutes and close to 100% within the first hour. That makes it clear that PRP should NOT be activated until it is ready to be used. As I have consistently suggested, PRP should not be activated at all except in vivo by the collagen that is abundant within most connective tissues.

Any comments on this paper would be appreciated.

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PRP activates Circulating Cells

The article referenced below discusses how locally injected PRP can mobilize cells to help heal a tendon. This provides solid mechanistic evidence to use PRP for tendon injuries and disorders and helps explain the positive clinical results. It is an excellent study and the authors have contributed significantly to our understanding of how PRP works.

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Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.

Kajikawa Y, Morihara T, Sakamoto H, Matsuda KI, Oshima Y, Yoshida A, Nagae M, Arai Y, Kawata M, Kubo T.

J. Cell Physiology Jan. 2008

Circulation-derived cells play a crucial role in the healing processes of tissue. In early phases of tendon healing processes, circulation-derived cells temporarily exist in the wounded area to initiate the healing process and decrease in number with time. We assumed that a delay of time-dependent decrease in circulation-derived cells could improve the healing of tendons. In this study, we injected platelet-rich plasma (PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and compared the effects on activation of circulation-derived cells and enhancement of tendon healing with a control group (no PRP injection). To follow the circulation-derived cells, we used a green fluorescent protein (GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the numbers of GFP-positive cells and heat-shock protein (HSP47; collagen-specific molecular chaperone)-positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of circulation-derived cells for enhancement of the initial tendon healing process. J. Cell. Physiol. (c) 2008 Wiley-Liss, Inc.

Total Tendon Network

A new network of both Patients and Providers has been created to improve the diagnosis and treatment of tendon related injuries and disorders. Discussion groups, pictures and video can be posted on this FREE network. Patients and Providers (Surgeons, Phyisicans, Physical Therapist etc) have joined from North America, Europe, South American, Australia and Asia.

Joining is simple and FREE.

Click here to sign up for the Total Tendon Network.

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American Academy of Orthopedic Surgery Article

Dr. Mishra's recent trip to Europe was featured in the American Academy of Orthopedic Surgery's Magazine: AAOS Now. The article titled "AAOS fellow takes European PRP Tour" was feature in the Jan. 2008 issue. The picture above is Dr. Mishra assisting on a platelet rich plasma enchanced achilles tendon repair in Sweden.


Click here to view AAOS Platelet Rich Plasma view article

Another sports medicine meeting in Chamonix France focusing on PRP will take place at the end of Jan 2008. Details of both meetings will be posted here soon.

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PRP Stimulates the greatest number of genes

According to recent reports from BEVA 2007, Cornell researchers examined the use of platelet-rich plasma (PRP) in horses with tendon injury, according to Schramme (Schnabel et al., Journal of Orthopedic Research, 2007). "The rationale is that if platelets release considerable growth factors, you could help with the healing of cartilage, tendons, ligaments)," he said.

"This study looked at gene expression patterns, DNA, and collagen content of equine tendon explants cultured (in vitro) with whole blood, plasma, and platelet-rich plasma," he continued. Concentrations of TGF-â1 and PDGF were higher in PRP-treated tendons, compared to other blood products and bone marrow."

Schramme commented that all blood products stimulate gene expression, PRP seemed to stimulate the greatest number of genes (collagen types II and III, and COMP), with no c with no concomitant (accompanying) increase in molecules of harmful enzymes. "These findings support in vivo (in the live animal) investigation of 100% PRP as an autogenous (generated in the body), patient-side treatment for tendonitis," he noted. "It's another treatment that we need to carefully evaluate in vivo as it continues to come along.

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