PRP enhances healing after Achilles Tendon Rupture

PRP being added to an Achilles Tendon Repair

If you rupture your Achilles tendon, new data suggests platelet rich plasma can enhance the healing.  In an abstract published by the journal Lancet, researchers from England discussed how they treated patients who had ruptured their Achilles with either PRP or a placebo.  Six weeks later, they biopsied the healing tendons under ultrasonic guidance.  In the study, they found improved cell content, better tendon fiber structure and more normal collagen (type 1) in the tendons treated with PRP.  The study included 20 patients (10 PRP, 10 Control) and is the first investigation in humans showing the significant value of using PRP to help treat Achilles tendon ruptures.  Of course, more data will be needed to confirm these important findings.  For years, I have been adding PRP to my achilles tendon repairs and if I ever rupture my own, I will certainly request that PRP is included in the treatment protocol.

AM 

Total Tendon

Tennis Elbow Stretches

Tennis elbow is a very common problem.  Most often it can be treated with rest, activity modification and some simple exercises.

Check out the TotalTendon Tennis Elbow Stretching Protocol.



In future posts, I will demonstrate a strengthening protocol and discuss other treatment options.

AM
TotalTendon

Why patients are seeking out platelet rich plasma and other biologic treatments.

Platelet rich plasma (PRP) and adult stem cell treatments derived from bone marrow are rapidly evolving into the mainstream of medicine.  As you can see from the chart above, the number of hits for "platelet rich plasma" is rising dramatically.  There are also over 7400 PRP references on PubMed.org.  Let's explore why.

Patients are seeking out less invasive treatments.  When presented with the option of surgery or an office procedure, patients typically will choose the office procedure.  Surgery often carries significant more risk and certainly more cost.

Patients want to return to sports, work or life as quickly as possible.
Botox and Lasik eye surgery provide patients with almost immediate improvement for wrinkles and vision.  Patients now expect other specialities to deliver similar almost instantaneous success.   Elite athletes are especially interested in returning to the highest level of function as quickly as possible.  They have been one of the primary drivers of PRP and other biologic treatments.

Patients are dissatisfied with the surgical treatments we have been offering them.
This is particularly true when it comes to knee arthritis.  Presently, there is very little definitive evidence supporting the use of many common treatments and there is a Grand Canyon size hole in our ability to effectively manage tens of millions of patients.  Biologic therapies will likely fill this void within the next five years.

Patients intuitively understand the regenerative abilities of your own blood and bone marrow.  Evidence is mounting across a several specialties supporting the use of blood and bone marrow to treat a variety of conditions.  A new study will begin this fall evaluating the utility of giving Alzheimer's patients blood transfusions from healthy volunteers under 30.  (Stanford Blood-Alzheimer's study)

Patients are willing to be treated without perfect supporting data.

Patients do not often understand the need for large clinical trials and are impatient with the time and effort it takes to generate meaningful clinical data.  The use of their own blood (PRP) or bone marrow simply make sense to them and they are willing and often eager to try a new treatment instead of undergo surgery.

We are presently scrambling to figure out how to develop, execute and pay for the clinical trials needed to best understand how to utilize biologic orthopedic therapies.  The good news is:  hundreds of clinicians, researchers and medical device professionals are working diligently on dozens of new treatment options.

Please post any comments about why you may think patients and clinicians are using PRP, stem cells or other biologic treatments.

AM   (@BloodCure on Twitter)
TotalTendon

Stem Cells from the Rotator Cuff and Biceps Tendon

In a landmark study, Dr. Pietro Randelli and his colleagues found a population of cells within the rotator cuff and biceps tendon with stem cell like "characteristics (ie, they were self-renewing in vitro, clonogenic, and multipotent), as they could be induced to differentiate into different cell types-namely, osteoblasts, adipocytes, and skeletal 

muscle cells."

The full implications of this paper are difficult to predict but this work could enable entirely new approaches to tendon repair within and outside of the shoulder.  The authors should be congratulated on this truly important work.  See the full abstract below for details.

AM
Total Tendon

Am J Sports Med. 2013 Feb 7. [Epub ahead of print]

Isolation and Characterization of 2 New Human Rotator Cuff and Long Head of Biceps Tendon Cells Possessing Stem Cell-Like Self-Renewal and Multipotential Differentiation Capacity.

Randelli P, Conforti E, Piccoli M, Ragone V, Creo P, Cirillo F, Masuzzo P, Tringali C, Cabitza P, Tettamanti G, Gagliano N, Anastasia L.

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Source

IRCCS Policlinico San Donato, San Donato Milanese, Italy.

Abstract

BACKGROUND:Stem cell therapy is expected to offer new alternatives to the traditional therapies of rotator cuff tendon tears. In particular, resident, tissue-specific, adult stem cells seem to have a higher regenerative potential for the tissue where they reside. HYPOTHESIS:Rotator cuff tendon and long head of the biceps tendon possess a resident stem cell population that, when properly stimulated, may be induced to proliferate, thus being potentially usable for tendon regeneration. STUDY DESIGN:Controlled laboratory study. METHODS:Human tendon samples from the supraspinatus and the long head of the biceps were collected during rotator cuff tendon surgeries from 26 patients, washed with phosphate-buffered saline, cut into small pieces, and digested with collagenase type I and dispase. After centrifugation, cell pellets were resuspended in appropriate culture medium and plated. Adherent cells were cultured, phenotypically characterized, and then compared with human bone marrow stromal cells (BMSCs), as an example of adult stem cells, and human dermal fibroblasts, as normal proliferating cells with no stem cell properties. RESULTS:Two new adult stem cell populations from the supraspinatus and long head of the biceps tendons were isolated, characterized, and cultured in vitro. Cells showed adult stem cell characteristics (ie, they were self-renewing in vitro, clonogenic, and multipotent), as they could be induced to differentiate into different cell types-namely, osteoblasts, adipocytes, and skeletal muscle cells. CONCLUSION:This work demonstrated that human rotator cuff tendon stem cells and human long head of the biceps tendon stem cells can be isolated and possess a high regenerative potential, which is comparable with that of BMSCs. Moreover, comparative analysis of the sphingolipid pattern of isolated cells with that of BMSCs and fibroblasts revealed the possibility of using this class of lipids as new possible markers of the cell differentiation status. CLINICAL RELEVANCE:Rotator cuff and long head of the biceps tendons contain a stem cell population that can proliferate in vitro and could constitute an easily accessible stem cell source to develop novel therapies for tendon regeneration.

Systemic Effects of Platelet Rich Plasma

In a well done study, researchers have shown when athletes are given an intratendinous injection of leukocyte-enriched platelet rich plasma (PRP), they will have elevated levels of growth factors in their blood up to four days after the procedure.  (see abstract below)

Vascular-endothelial growth factor  (VEGF), a molecule known to enhance angiogenesis (new blood vessel formation), was elevated in all 25 patients after injection.  This is very interesting and important data suggesting PRP may trigger a systemic response.  It also helps explain why PRP may be a useful treatment for tendon related injuries and disorders.   Several controlled studies confirm PRP can be an effective treatment for chronic tennis elbow and this study may reveal one of the mechanisms of action.
Tennis Elbow Study 1,  Tennis Elbow Study 2

It would be quite interesting and important to also measure growth factors in athletes who have received a saline injection or dry needling of their tendons to see if the act of introducing a needle into a damaged tendon produces a similar or different systemic response.

AM
TotalTendon.com

Am J Sports Med. 2012 Dec 4.

The Systemic Effects of Platelet-Rich Plasma Injection.

Wasterlain AS, Braun HJ, Harris AH, Kim HJ, Dragoo JL.

Source

Department of Orthopaedic Surgery, Stanford University, Stanford, California.

Abstract

BACKGROUND:Platelet-rich plasma (PRP) is an autologous blood product used to treat acute and chronic tendon, ligament, and muscle injuries in over 86,000 athletes in the United States annually. The World Anti-Doping Agency (WADA) banned intramuscular PRP injections in competitive athletes in 2010 because of concerns that it may increase performance-enhancing growth factors. The ban on PRP was removed in 2011 because of limited evidence for a systemic ergogenic effect of PRP, but the growth factors within PRP remain prohibited. PURPOSE:To quantify the effect of PRP injection on systemic growth factors with performance-enhancing effects and to identify molecular markers to detect treated athletes. STUDY DESIGN:Descriptive laboratory study. METHODS:Six ergogenic growth factors monitored by WADA-human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB)-were measured in 25 patients before (baseline) and at 0.25, 3, 24, 48, 72, and 96 hours after intratendinous leukocyte-rich PRP injection. Eating and exercise were prohibited for 3 hours before testing. Growth factors were quantified by enzyme-linked immunosorbent assay, and the change relative to each patient's baseline was calculated. RESULTS:Relative to serum, PRP contained significantly more bFGF (226 vs 5 pg/mL), VEGF (1426 vs 236 pg/mL), and PDGF-BB (26,285 vs 392 pg/mL), but IGF-1 and hGH were not elevated. Serum levels increased significantly for IGF-1 at 24 and 48 hours, for bFGF at 72 and 96 hours, and for VEGF at 3, 24, 48, 72, and 96 hours after PRP injection. Additionally, VEGF was increased in all 25 patients after PRP treatment. CONCLUSION:Serum IGF-1, VEGF, and bFGF levels are significantly elevated after PRP injection, supporting a possible ergogenic effect of PRP. An indirect marker for hGH doping, the product of IGFBP-3 × IGF-1, also significantly increased after PRP. Platelet-rich plasma appears to trigger an increase in circulating growth factors through activating biological pathways rather than by serving as a vehicle for the direct delivery of presynthesized growth factors. Elevated VEGF was observed in all patients after PRP, and ≥88% of patients had elevated VEGF at each time point from 3 to 96 hours after PRP, suggesting that VEGF may be a sensitive molecular marker to detect athletes recently treated with PRP. CLINICAL RELEVANCE:This is the first and only adequately powered study of the systemic effects of PRP. We present evidence that PRP contains and may trigger systemic increases in substances currently banned in competitive athletes. Finally, we provide evidence that VEGF could serve as a useful molecular marker to detect athletes treated with PRP.

NFL grants $100,000 to study PRP and Stem Cells for Tendon Disorders

The National Football League recently granted $100,000 to the Hospital for Special Surgery to study the effects of platelet rich plasma and stem cells on tendons.  The research will be conducted by Dr. Scott Rodeo, associate team physician for the New York Giants.  The focus will be to better understand the effects of different formulations of PRP in a preclinical model.  Specific evaluations of how PRP influences the tendon structure will be done.

This is important research that should help answer multiple questions.  Clinical studies to date have been variable in their outcomes.  The best available data today supports the use of PRP with white blood cells injected in an unactivated form for chronic tennis elbow.  We need to better understand the mechanisms underlying various forms of PRP in order to best apply it clinically.

We will all be most interested in following the results of their investigations.

See full article about research grant. 

Allan Mishra
TotalTendon
@BloodCure

Steroid Injections may Deplete Tendon Stem Cell Pools

Steroid injections are commonly used for a number of musculoskeletal conditions.  There is increasing evidence to suggest this is not a good idea especially for tendon related problems such as tennis elbow or rotator cuff tendinopathy.  Clinical studies only confirm short term pain relief for cortisone injections.  Basic science studies are now revealing that such injections may deplete tendon stems cells pools or increase the risk of tendon rupture.  (See Abstract Below)

Platelet rich plasma has been shown to be superior to cortisone injection in a double blind randomized trial at least for tennis elbow.  When discussing the value of evolving biologic therapies it is crucial to compare them to commonly used treatments.  In the case of cortisone for tendon related injuries and disorders at least for now PRP is the superior choice based on basic science and clinical publications for tennis elbow.  (Gosens et al Study)

Allan Mishra, MD

@Bloodcure
TotalTendon

J Orthop Res. 2012 Aug 8. 

The effects of dexamethasone on human patellar tendon stem cells: Implications for dexamethasone treatment of tendon injury.

Zhang J, Keenan C, Wang JH.

Source

Abstract

Injection of Dexamethasone (Dex) is commonly used in clinics to treat tendon injury such as tendinopathy because of its anti-inflammatory capabilities. However, serious adverse effects have been reported as a result of Dex treatment, such as impaired tendon healing and tendon rupture...... Dex treatment depletes the stem cell pool and leads to the formation of non-tendinous tissues (e.g., fatty and cartilage-like tissues), which make tendon susceptible to rupture. 

© 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 

Copyright © 2012 Orthopaedic Research Society.

See Full Abstract

PRP Enhances Tendon Vascularity

Platelet rich plasma is now being used worldwide for tendon related injuries and disorders. Increased vascularity is one of the proposed mechanism of action for PRP. In the study outlined below, this hypothesis is supported in an achilles tendon injury model.

The poor vascularity of tendons is a major factor in their limited healing capacity. The aim of this study was to assess the effect of Platelet Rich Plasma (PRP) on angiogenesis during tendon healing. MATERIALS AND METHODS: Forty-eight skeletally mature New Zealand White rabbits were used. The Achilles tendon was transected transversely and 0.5 ml of PRP was injected into the tendon mass on each side of the incision on both limbs. The injection in the control group consisted of saline. Six animals from each group (12 tendons each) were sacrificed after 1, 2, 3, and 4 weeks following treatment. Three sections from each Achilles were stained with hematoxylinosin for microscopic examination. Further three sections were immunostained with a monoclonal antibody against CD31 (Daco Co), followed by image analysis to count new vessel numbers and statistical analysis was performed. RESULTS: There was significantly more angiogenesis in the PRP group compared to the control group during the first two weeks of the healing process, i.e., inflammatory and proliferative phase (p <> Lyras et al.

AM

San Francisco Chronicle Article: "Miracle Cure"

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

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