Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.
ABSTRACT 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.
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ABSTRACT: Different intrinsic properties of the constituent cells of the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) have been proposed to be one of the factors in the differential repair mechanisms. We have found that the outgrowth of cells from rabbit ACL explants was slower than from MCL explants after 10 d. Growth curves of ACL and MCL cultures at both Passage numbers 2 and 6 showed a slower rate of proliferation of ACL cells than MCL cells (P < 0.005). The proliferative response of rabbit ACL and MCL cells to b-FGF and TGF-beta was also investigated. Both b-FGF and TGF-beta had no significant effect on cell proliferation of ACL and MCL cultures after 48 h. However, TGF-beta did have an inhibitory effect on thymidine incorporation, especially at concentrations greater than 1 ng.ml-1, while b-FGF stimulated thymidine incorporation in ACL and MCL in a dose-dependent manner. Differences in the cell morphology of the ACL and MCL cells grown in culture were seen also. Cells from Passages 3-6 demonstrated these differences more prominently, and phalloidin staining for actin showed that ACL cells appeared to have more intracellular actin fibers.Medicine & Science in Sports & Exercise 06/1995; 27(6):844-51. · 4.48 Impact Factor
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ABSTRACT: The effects of splintage, suture and excision of the tendon sheath on the healing of incompletely transected flexor tendons in the rabbit have been evaluated separately and in various combinations. When all procedures were done together, repair was accompanied by dense adhesion formation with little evidence of any healing activity by the tendon cells. The experiments indicated that the adhesions were the result not of any one single factor studied but of all three contributing in varying degrees. Suturing produced the most adhesions but synovial sheath excision and immobilisation also contributed. It is suggested that these factors are also responsible for the adhesions which occur after flexor tendon repair in clinical practice.Journal of Bone and Joint Surgery - British Volume 06/1976; 58(2):230-6. · 2.69 Impact Factor
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ABSTRACT: Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Tendons were cultured in explant fashion with blood, plasma, PRP, PPP, or BMA at concentrations of 100%, 50%, or 10% in serum-free DMEM with amino acids. Quantitative RT-PCR for expression of collagen type I (COL1A1), collagen type III (COL3A1), cartilage oligomeric matrix protein (COMP), decorin, matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) was performed as were DNA and total soluble collagen assays. TGF-beta1 and PDGF-BB concentrations were higher in PRP compared to all other blood products tested. Tendons cultured in 100% PRP showed enhanced gene expression of the matrix molecules COL1A1, COL3A1, and COMP with no concomitant increase in the catabolic molecules MMP-3 and MMP-13. These findings support in vivo investigation of PRP as an autogenous, patient-side treatment for tendonitis.Journal of Orthopaedic Research 03/2007; 25(2):230-40. · 2.88 Impact Factor
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
Research, use of platelet-rich plasma continues to expand
Platelet-rich plasma (PRP)—a component of whole blood containing powerful, transforming growth factors—has
garnered worldwide attention as a possible biologic method to treat tendinosis and tendon tears, as well as many
other challenging conditions.
In Europe, PRP is being used to treat conditions ranging from tendinosis to osteitis pubis. This past November, I had
the opportunity to take a European “PRP Tour”—to share my clinical work on PRP and to learn about and witness
how European orthopaedists are using PRP to enhance healing. I was also invited to speak at several meetings
focused on research and clinical experiences with PRP.
Achilles tendon repair in Sweden
Upon my arrival in Linköping, about two hours west of Stockholm by train, I met with Per Aspenberg, MD, PhD, the
author of several articles on the successful use of PRP to enhance tendon healing. We discussed the number of
researchers around the world who are investigating and assessing the value of PRP in orthopaedic surgery.
The next morning, I was asked if I would like to observe Dr. Aspenberg and his colleague, Torsten Schepull, MD,
perform an Achilles tendon repair. I welcomed the opportunity. The nurses and operating room staff were very cordial
and, fortunately for me, spoke excellent English.
As the patient was prepped for surgery, I was asked whether I would like to scrub in on the case. The patient was
lightly sedated and in a prone position; a local anesthetic was injected around the incision site. After the surgery had
started, I was informed that this patient was the first case in a prospective, randomized trial to measure the impact of
receiving autologous PRP in an Achilles tendon repair.
The lead surgeon made the incision, expertly mobilizing the tendon edges. After checking the treatment allocation
data on the computer, the surgeons found that this patient would receive PRP. Although the patient was awake,
headphones prevented him from hearing any of the discussion, so he remained unaware of the randomization
decision. To ensure the accuracy of the research, no further discussion on the use of PRP was permitted around this
Just before the surgeon closed the tendon sheath, he embedded 0.8 mm tantalum balls into the tendon above and
below the tear site. This allows for noninvasive analysis of tendon elongation at 6- to 10-week intervals postsurgery.
Researchers will be able to calculate and compare tendon length among patients in the PRP group and those in the
control group. I found this to be a particularly unique and novel method, which will provide information for the clinical
trial and additional noninvasive biomechanical data on the differences between the two groups. The PRP was
injected into and around the repaired tendon after the surgeon closed the tendon sheath.
Other uses for PRP
In the afternoon, orthopaedic surgeons from throughout northern and Eastern Europe attended a meeting to discuss
their research and clinical experiences with PRP.
From his studies with rat models, Dr. Aspenberg demonstrated how PRP enhances Achilles tendon stiffness and
force to failure. Taco Grosen, MD, from the Netherlands, presented preliminary data from his prospective,
randomized trial of PRP versus cortisone for treating chronic tennis elbow.
Dr. Grosen demonstrated how PRP produces significantly better statistical outcomes than cortisone for pain relief and
functional scoring at 6 months after a single injection. This is consistent with my findings in “Treatment of Chronic
Elbow Tendinosis with Buffered Platelet-Rich Plasma,” published in the American Journal of Sports Medicine.
Orthopaedic surgeons from Sweden, Finland, and Poland also made presentations on PRP. Ongoing investigations
include the use of PRP in the treatment of partial tears of the anterior cruciate ligament (ACL), meniscal tears, and
Krzysztof Ficek, MD, from Poland, reported that he has some success using PRP with osteitis pubis—a notoriously
difficult condition. Eight of nine patients treated with PRP are doing very well.
Italian Ministry of Health funds PRP study
At the Galeazzi Orthopedic Institute, in Milan, I met with Professor Giuesppe Banfi and Laura de Girolamo, MD, about
their prospective study of tendinosis funded by the Italian Ministry of Health.
We discussed the confusion they routinely encounter in Italy about the growth factors in PRP. Some patients and
Italian ministry administrators think growth factors are growth hormones. Part of their job is convincing patients and
administrators that PRP is not a growth hormone!
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Drs. Banfi and Girolamo provided the following statement about their study. “All the patients suffer from chronic
osteoarticular pathology and are exposed to a nonsteroidal anti-inflammatory drug (NSAID) therapy. They will
undergo either anterior cruciate ligament reconstruction surgery with PRP or Achilles/patellar tendon surgery with
PRP and will be clinically evaluated for 12 months according to a predetermined protocol.
“A biopsy of the patient’s cartilage tissue will be evaluated by other centers during an in-vitro study culturing the
patient’s chondrocytes with their PRP. The aim of the in-vitro study is to evaluate a number of inflammatory markers
and molecular ‘targets’ implicated in the inflammatory and healing response of the cartilage taken from patients
exposed to NSAID and to the PRP treatment, which in the future might be used for diagnostic and therapeutic
The investigators have asked me to evaluate their protocol and to contribute to their study.
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Genoa: PRP and the treatment of tendinopathy
In Italy, I also attended the 15th annual meeting of the Ligurian Arthroscopy Association organized by Ferdinando
Priano, MD. I had been asked to give two lectures—one on the basic science of PRP and the other on my own
clinical experiences with it.
With more than 300 orthopaedic surgeons, basic scientists, and hematologists in attendance, the meeting focused on
the potential use of PRP in the treatment of tendinopathy.
Dr. Priano shared his experience using hyaluronic acid for tendon-related disorders. Piero Volpi, MD, presented the
results of a study using ultrasonic guided injections of PRP for patellar tendinosis. Pietro Randelli, MD, showed an
excellent video of his technique using PRP to augment arthroscopic rotator cuff repairs.
My week in Europe showed me that interest in PRP as a treatment to enhance healing has grown quite dramatically,
with speculation about using this technology for cartilage, ligament, and even disk pathology. Significantly more basic
science and clinical investigations, however, will be required to fully validate the use of PRP.
I plan to continue these interactions with my esteemed European colleagues via the Internet and in person at future
meetings. I have been honored to be part of the PRP discussions in both the United States and Europe. I recently
learned that orthopaedic surgeons in Brazil, Australia, and Hong Kong have also used PRP in orthopaedic surgery. I
look forward to hearing the results from my orthopaedic colleagues throughout the world.
Disclosure information for Allan K. Mishra, MD, can be found online at www.aaos.org
Dr. Mishra can be reached at email@example.com
How does PRP work?
Platelet-rich plasma (PRP) contains powerful growth factors. including transforming growth factor-beta (TGF-β) and
vascular endothelial growth factor (VEGF). PRP has been shown to enhance the proliferation and migration of a
variety of cell types including tenocytes and mesenchymal stem cells. This in-vitro data helps explain why PRP may
be helpful for patients with chronic tendinosis. Published studies also note that PRP has a strong stimulant effect on
capillary regeneration. This improved vascularity may be another way PRP improves overall tendon health.
Not all PRP is the same. PRP that has not been activated by thrombin or calcium may be the preferred form. The
collagen within tendons can be expected to activate the platelets slowly, resulting in a sustained release of growth
factors. PRP activated by thrombin and or calcium, however, results in rapid discharge of growth factors, which may
not be ideal.
Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med.
Mishra et al. Buffered Platelet Rich Plasma Enhances Mesenchymal Stem Cell Proliferation and Chondrogenic
Differentiation. AAOS Annual Meeting; Poster Presentation, 2007
Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet rich plasma:
implications for wound healing. Plast Reconstr Surg. 2004 Nov:114(6):1502-8
Schnabel LV, Mohammed HO, Miller BJ, et al. Platelet rich plasma (PRP) enhances anabolic gene expression
patterns in flexor digitorum superficialis tendons. J Ortho Res. 2007 Feb;25(2):230-240
Woodall JR, Tucci M, Mishra A, Benghuzzi H. Cellular Effects of Platelet Rich Plasma: A Study on HL-60
Macrophage-like Cells. Biomed Sci Instrum. 2007, 43:266-71