Thursday, May 24, 2012

Platelet Rich Plasma Significantly Improves Pain and Function for Patellar Tendonitis

In a randomized controlled trial, platelet rich plasma significantly improved pain and function in patients with patellar tendinopathy (also known as patellar tendonitis).  In the study, PRP was compared to dry needling.  The PRP used in the study contained concentrated platelets and white blood cells, also known as leukocytes (prepared via the Biomet Biologics GPS system).   Both groups were also given an eccentric exercise program.

“Importantly, we also showed that PRP is both clinically and statistically significantly better than dry needling based on the Victorian Institute of Sports Assessment  (VISA) score of patella tendinopathy symptoms.”  (See Full Article)



MRI showing significant patellar tendinopathy


This important data contributes significantly to the growing body of evidence suggesting PRP has value in the treatment of tendon related disorders.  


AM (@bloodcure)
Total Tendon

Thursday, May 17, 2012

Stem Cells Enhance Function after Spinal Cord Injury

In the study outlined below, researchers injected bone marrow derived stem cells that had been expanded in culture into patients with spinal cord injuries.  Sixty percent of the patients noted improvement in their motor function after the treatment.  Importantly, there were no complications.  This is an important first study validating the approach.  The details of why some patients responded and others did not will be crucial to planning further trials. 

AM

Neurosurgery. 2012 May;70(5):1238-47.
Long-term Results of Spinal Cord Injury Therapy Using Mesenchymal Stem Cells Derived From Bone Marrow in Humans.

Park JH, Kim DY, Sung IY, Choi GH, Jeon MH, Kim KK, Jeon SR.

SourceDepartments of *Neurological Surgery ‡Rehabilitation Medicine §Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract
BACKGROUND: : Although the transplantation of mesenchymal stem cells (MSCs) after spinal cord injury (SCI) has shown promising results in animals, less is known about the effects of autologous MSCs in human SCI.

OBJECTIVE: : To describe the long-term results of 10 patients who underwent intramedullary direct MSCs transplantation into injured spinal cords.

METHODS: : Autologous MSCs were harvested from the iliac bone of each patient and expanded by culturing for 4 weeks. MSCs (8 × 10) were directly injected into the spinal cord, and 4 × 10 cells were injected into the intradural space of 10 patients with American Spinal Injury Association class A or B injury caused by traumatic cervical SCI. After 4 and 8 weeks, an additional 5 × 10 MSCs were injected into each patient through lumbar tapping. Outcome assessments included changes in the motor power grade of the extremities, magnetic resonance imaging, and electrophysiological recordings.

RESULTS: : Although 6 of the 10 patients showed motor power improvement of the upper extremities at 6-month follow-up, 3 showed gradual improvement in activities of daily living, and changes on magnetic resonance imaging such as decreases in cavity size and the appearance of fiber-like low signal intensity streaks. They also showed electrophysiological improvement. All 10 patients did not experience any permanent complication associated with MSC transplantation.

CONCLUSION: : Three of the 10 patients with SCI who were directly injected with autologous MSCs showed improvement in the motor power of the upper extremities and in activities of daily living, as well as significant magnetic resonance imaging and electrophysiological changes during long-term follow-up.



ABBREVIATIONS: : ADL, activities of daily livingASIA, American Spinal Injury AssociationBM, bone marrowMEP, motor evoked potentialMSC, mesenchymal stem cellP, passageSCI, spinal cord injury.



Wednesday, May 09, 2012

Treatment of Wounds with Platelet Rich Plasma: Proposed Coverage by Medicare

In a landmark decision "the Centers for Medicare & Medicaid Services("CMS") issued a proposed National Coverage Determination ("NCD") memo for autologous blood-derived products for chronic non-healing wounds. In its decision memo CMS has proposed coverage through its Coverage with Evidence Development ("CED") program for all three major wound categories: diabetic, venous and pressure wounds."  CMS also, "believes that  PRP may have the potential to benefit Medicare beneficiaries." 


This decision marks an important turning point for platelet rich plasma and autologous blood based products in general.  The value of PRP for specific clinical problems will continue to rise as data is generated supporting it for specific applications.  


Read more about it via this article.


AM
Total Tendon

Systematic Analysis reveals Platelet Rich Plasma improves Rotator Cuff Repair Surgery

Improving the healing rates for rotator cuff repair surgery has been an important goal in orthopedic surgery for years. Recently, platelet rich plasma has been proposed as a potential biologic adjuvant to rotator cuff repair.  Several studies have been published on the topic with conflicting results.  This data variability can be traced to the variety of PRP formulations being used and the types of tears being repair.

Recent, Brian Cole and his colleagues at Rush, released information about a systematic analysis of the PRP rotator cuff literature.  "Their review revealed that the re-tear rate for small and medium tears treated at the time of surgery with PRP was 7.9 percent, compared to a re-tear rate of 26.8 percent when PRP was not used. The results will be published in the Journal of Arthroscopy this summer.
We are still at the beginning of understanding how to use PRP for rotator cuff repairs.  This review, however, clearly suggest PRP may be of value for small or medium sized tears.  Further details and analysis will be provided about publication of the paper. 

AM

TotalTendon

" (Reference site)

Tuesday, May 08, 2012

Lose 5 pounds, your knees will feel as if you lost 25 pounds.





The forces supporting your knees are complex but the math is simple.  About 4-6 times your body weight is transmitted through your knee joint when you simply walk.  Think about that fact for a second.  If you weigh 200 pounds, your knee experiences 1000 pounds of force while strolling down the street.

Importantly, being overweight is a "clear risk factor" for knee osteoarthritis.  For women, being overweight increases this risk 4 times higher.  For men, the risk increases 5 fold in patients who are overweight.  Dropping as little as 10 pounds may be enough to significantly lower this risk.

There are no simple solutions to weight loss.  One suggestion I give my patients is to try the "One Less, One More" plan.  Try it for a week.  One less beer, one less glass of wine, one less bagel, one less serving of ice cream.  One more time taking the stairs, one more trip to the gym, one more walk around the block.

For more information about knee osteoarthritis and being overweight with references for the data outlined about, click here.

Allan Mishra, MD
Send thoughts/ideas about how to lose weight to:  @bloodcure

Thursday, May 03, 2012


Platelet Rich Plasma stimulates rotator cuff cells to proliferate and enhances matrix synthesis.

This is a basic science study using tenocytes from degenerative rotator cuffs.  The data suggests platelet rich plasma helped increase cell proliferation and also increased collagen synthesis.  This speaks to the importance of formulation and application when using PRP.  The clinical data for rotator cuff pathology is not consistent.  We need larger studies applying specific formulations such as the one in this study to determine if their is clinical value of PRP for patients with rotator cuff tears.  See abstract below.  


Am J Sports Med. 2012 May;40(5):1035-45. Epub 2012 Feb 23.

Platelet-rich plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes from human rotator cuff tendons with degenerative tears.

Source

Chris Hyunchul Jo, Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 41 Boramae-gil, Dongjak-gu, 156-707 Seoul, Korea. 

Abstract

BACKGROUND:

Platelet-rich plasma (PRP) contains various growth factors and appears to have a potential to promote tendon healing, but evidence is lacking regarding its effect on human tenocytes from rotator cuff tendons with degenerative tears.

HYPOTHESIS:

Platelet-rich plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes isolated from human rotator cuff tendons with degenerative tears.

STUDY DESIGN:

Controlled laboratory study.

METHODS:

Tenocytes were enzymatically isolated and cultured. To evaluate cell proliferation, tenocytes were cultured with 10% (vol/vol) platelet-poor plasma (PPP), PRP activated with calcium, and PRP activated with calcium and thrombin at platelet concentrations of 100, 200, 400, 800, 1000, 2000, 4000, 8000, and 16,000 × 10(3)/µL for 14 days. Cell number was measured at days 7 and 14. To investigate matrix gene expression and synthesis, cells were cultured with a PPP or PRP gel (10% vol/vol) at a platelet concentration of 1000 × 10(3)/µL for 14 days. Quantitative real-time reverse transcriptase polymerase chain reaction was performed to determine the expressions of type I and III collagen, decorin, tenascin-C, and scleraxis, and measurements of total collagen and glycosaminoglycan (GAG) synthesis were conducted at days 7 and 14.

RESULTS:

Platelet-rich plasma significantly increased cell proliferation at days 7 and 14 in a dose-dependent manner, and the addition of thrombin moved up the plateau of proliferation. Platelet-rich plasma significantly induced the gene expression of type I collagen at day 7 but not at day 14, while it significantly promoted that of type III both at days 7 and 14. The ratio of type III/I collagens did not change at days 7 and 14. The expressions of decorin and scleraxis significantly increased at day 14, whereas that of tenascin-C significantly increased at days 7 and 14. Platelet-rich plasma significantly increased total collagen synthesis at days 7 and 14 and GAG synthesis at day 14.

CONCLUSION:

Platelet-rich plasma promoted cell proliferation and enhanced gene expression and the synthesis of tendon matrix in tenocytes from human rotator cuff tendons with degenerative tears.

CLINICAL RELEVANCE:

These findings suggest that PRP might be used as a useful biological tool for regenerative healing of rotator cuff tears by enhancing the proliferation and matrix synthesis of tenocytes from tendons with degenerative tears.

Wednesday, May 02, 2012


Genes Identified that are Associated with Risk of Fracture

In the study outlined below, genes were identified that are associated with increased risk of fracture.  Importantly, six genes NOT known to have a role in bone biology were found to correlate with bone mineral density.  This speaks to the importance of looking for diseases related genes within AND outside of known pathways.  See abstract below.


Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Nature Genetics
 
44,
 
491–501
 
(2012)
Received
 
Accepted
 
Published online
 



Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Umbilical cord blood-derived platelet rich plasma more potent than adult platelet rich plasma.

Platelet rich plasma derived from umbilical cord blood (ucPRP) was compared to adult PRP.  In the study outlined below, the ucPRP had greater potency than adult PRP in terms of stem cell proliferation and chemotaxis (ability to have cells migrate).  Very interesting work.  See abstract below.


AM
Total Tendon


Adult and umbilical cord blood-derived platelet-rich plasma for mesenchymal stem cell proliferation, chemotaxis, and cryo-preservation.

Source

Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX 77025, USA; Center for Stem Cell Research, Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Abstract

Platelet-rich plasma (PRP) was prepared from human adult peripheral blood and from human umbilical cord (uc) blood and the properties were compared in a series of in vitro bioassays. Quantification of growth factors in PRP and platelet-poor plasma (PPP) fractions revealed increased levels of mitogenic growth factors PDGF-AB, PDGF-BB, and FGF-2, the angiogenic agent VEGF and the chemokine RANTES in ucPRP compared to adult PRP (aPRP) and PPP. To compare the ability of the various PRP products to stimulate proliferation of human bone marrow (BM), rat BM and compact bone (CB)-derived mesenchymal stem cells (MSC), cells were cultured in serum-free media for 4 and 7 days with varying concentrations of PRP, PPP, or combinations of recombinant mitogens. It was found that while all forms of PRP and PPP were more mitogenic than fetal bovine serum, ucPRP resulted in significantly higher proliferation by 7 days than adult PRP and PPP. We observed that addition of as little as 0.1% ucPRP caused greater proliferation of MSC effects than the most potent combination of recombinant growth factors tested, namely PDGF-AB + PDGF-BB + FGF-2, each at 10 ng/mL. Similarly, in chemotaxis assays, ucPRP showed greater potency than adult PRP, PPP from either source, or indeed than combinations of either recombinant growth factors (PDGF, FGF, and TGF-β1) or chemokines previously shown to stimulate chemotactic migration of MSC. Lastly, we successfully demonstrated that PRP and PPP represented a viable alternative to FBS containing media for the cryo-preservation of MSC from human and rat BM.
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