PKh:cwrefs.MYD<7CAnitua, E. Sanchez, M. Nurden, A. T. Nurden, P. Orive, G. Andia, I.2006KNew insights into and novel applications for platelet-rich fibrin therapies227-34Trends Biotechnol245*Blood Platelets Fibrin/*therapeutic use Fractures, Bone/*therapy Humans Musculoskeletal Diseases/*therapy Platelet Transfusion/*methods/trends Soft Tissue Injuries/*therapy Tissue Engineering/*methods/trendsMay The therapeutic use of autologous platelet-rich plasma constitutes a relatively new biotechnology that has been a breakthrough in the stimulation and acceleration of soft-tissue and bone healing. The efficiency of this process lies in the local and continuous delivery of a wide range of growth factors and proteins, mimicking the needs of the physiological wound healing and reparative tissue processes. Consequently, the application of platelet-rich plasma has been extended to many different fields, including orthopedics, sports medicine, dentistry, cosmetic and periodontal medicine and cosmetic, plastic and maxillofacial surgery. This article highlights the use of this technology and discusses some of the obstacles and challenges that need to be addressed to maintain progress in this field.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16540193 ?Journal Article Research Support, Non-U.S. Gov't Review England0167-7799 (Print)Trends in biotechnology16540193IBiotechnology Institute I MAS D, c/ San Antonio 15, 01005 Vitoria, Spain.eng <7+Cancedda, R. Giannoni, P. Mastrogiacomo, M.2007\A tissue engineering approach to bone repair in large animal models and in clinical practice4240-50 Biomaterials2829Animals Bone Diseases/*surgery *Bone Regeneration *Bone Substitutes *Bone Transplantation Clinical Medicine/methods *Disease Models, Animal Fractures, Bone/*surgery Humans Tissue Engineering/*methodsOctThe repair of large segmental bone defects due to trauma, inflammation and tumor surgery remains a major clinical problem. Animal models were developed to test bone repair by tissue engineering approaches, mimicking real clinical situations. Studies differed with regard to animals (dog, sheep, goat), treated bone (femur, tibia, mandible), chemistry and structure of the scaffolds. Still, an advantage in the bone formation and in the healing of the segmental defect was always observed when scaffolds were seeded with bone marrow derived stromal cells (BMSCs). In the year 1998 was performed the first implantation of a porous ceramic construct in a bone segmental defect of a patient; it was the first construct seeded with cultured autologous osteogenic cells. Since then, only few other similar cases were treated by the same approach. However, in other fields, such as oral and maxillofacial surgery, injectable cells/platelet-rich plasma composites have been used as grafting materials for maxillary sinus floor augmentation and/or onlay plasty. More recently, the reconstruction of a human mandible was also reported by means of a bone-muscle-flap in vivo prefabrication technique, where the patient served as his own bioreactor. Indeed continuous implementations test and provide new means of defects treatment and cure. However, based on results so far obtained in animal models and pilot clinical studies, one can affirm that the bone tissue engineering approaches, although successful in most cases, need further validation before a wide application in clinics. In particular, the supply of oxygen and nutrients to the cells in the inner part of the implanted scaffolds remains a major concern, requiring additional investigations.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17644173 ?Journal Article Research Support, Non-U.S. Gov't Review England0142-9612 (Print) Biomaterials17644173oIstituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genova, Italy. ranieri.cancedda@unige.iteng |7+Cara, D. C. Ebbert, K. V. McCafferty, D. M.2004TMast cell-independent mechanisms of immediate hypersensitivity: a role for platelets4964-71 J Immunol1728xAllergens/administration & dosage Animals Blood Platelets/*immunology Capillary Permeability/genetics/immunology Cell Adhesion/genetics/immunology Cell Communication/genetics/immunology Cell Movement/genetics/immunology Endothelium/blood supply/cytology/immunology Hypersensitivity, Immediate/*immunology/pathology/physiopathology Injections, Intraperitoneal Leukocytes/cytology/immunology Male Mast Cells/*immunology/pathology Mice Mice, Inbred C57BL Mice, Mutant Strains Muscle, Skeletal/blood supply/immunology/pathology Ovalbumin/administration & dosage/immunology Rats Rats, Sprague-Dawley Skin/blood supply/cytology/immunologyApr 15yMast cells have been implicated as the central effectors in allergic responses, yet a fatal anaphylactic response can be induced in mast cell-deficient mice. In this study, we examined the immediate hypersensitivity response in wild-type (WT) and mast cell-deficient mice (W/W(v)) in two different tissues (skin and skeletal muscle). Vascular permeability and leukocyte recruitment were studied after immediate challenge or 4 h postchallenge in OVA-sensitized mice. In skin, immediate challenge induced a significant increase in vascular permeability (75%) within 30 min and was accompanied by increased leukocyte adhesion 4 h postchallenge. In the absence of mast cells, no changes in vascular permeability or leukocyte recruitment were observed in skin. In WT skeletal muscle, immediate challenge induced a rapid increase (80%) in vascular permeability within 5 min and significant leukocyte recruitment after 4 h. Surprisingly, in W/W(v), a gradual increase in vascular permeability was observed, reaching a maximum (50%) within 30 min. Despite the absence of mast cells, subsequent leukocyte emigration was similar to that observed in WT mice. Pretreatment with anti-platelet serum in W/W(v) returned Ag-induced vascular permeability and leukocyte recruitment to baseline. Platelets were shown to interact with endothelium in skeletal muscle, but not dermal microvasculature. These data illustrate that mast cells play a prominent role in vascular permeability and leukocyte recruitment in skin in response to Ag, however, in skeletal muscle; these changes can occur in the absence of mast cells, and are mediated, in part, by the presence of platelets.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15067077 VComparative Study Journal Article Research Support, Non-U.S. Gov't United States 1950)0022-1767 (Print)15067077zGastrointestinal Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.eng <7Creaney, L. Hamilton, B.2008VGrowth factor delivery methods in the management of sports injuries: the state of play314-20Br J Sports Med425Animals Athletic Injuries/*drug therapy/pathology Doping in Sports/*legislation & jurisprudence Fibrosis/chemically induced Humans Injections Intercellular Signaling Peptides and Proteins/*administration & dosage/adverse effects Wound Healing/drug effectsMayIn recent years there have been rapid developments in the use of growth factors for accelerated healing of injury. Growth factors have been used in maxillo-facial and plastic surgery with success and the technology is now being developed for orthopaedics and sports medicine applications. Growth factors mediate the biological processes necessary for repair of soft tissues such as muscle, tendon and ligament following acute traumatic or overuse injury, and animal studies have demonstrated clear benefits in terms of accelerated healing. There are various ways of delivering higher doses of growth factors to injured tissue, but each has in common a reliance on release of growth factors from blood platelets. Platelets contain growth factors in their alpha-granules (insulin-like growth factor-1, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, vascular endothelial growth factor, transforming growth factor-beta(1)) and these are released upon injection at the site of an injury. Three commonly utilised techniques are known as platelet-rich plasma, autologous blood injections and autologous conditioned serum. Each of these techniques has been studied clinically in humans to a very limited degree so far, but results are promising in terms of earlier return to play following muscle and particularly tendon injury. The use of growth factors in sports medicine is restricted under the terms of the World Anti-Doping Agency (WADA) anti-doping code, particularly because of concerns regarding the insulin-like growth factor-1 content of such preparations, and the potential for abuse as performance-enhancing agents. The basic science and clinical trials related to the technology are reviewed, and the use of such agents in relation to the WADA code is discussed.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17984193 Journal Article Review England1473-0480 (Electronic)"British journal of sports medicine17984193mOlympic Medical Institute, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK. leoncreaney@hotmail.comeng <7dde Mos, M. van der Windt, A. E. Jahr, H. van Schie, H. T. Weinans, H. Verhaar, J. A. van Osch, G. J.2008DCan platelet-rich plasma enhance tendon repair? A cell culture study1171-8Am J Sports Med366jCell Proliferation Cells, Cultured Collagen Type I/*biosynthesis/genetics Collagen Type III/*biosynthesis/genetics DNA/analysis Gene Expression Humans Matrix Metalloproteinases/biosynthesis *Platelet-Rich Plasma Tendons/*cytology/metabolism Transforming Growth Factor beta1/biosynthesis Vascular Endothelial Growth Factor A/biosynthesis Wound Healing/*physiologyJun4BACKGROUND: 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 I alpha 1 (COL1) and III alpha 1 (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.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18326832 Journal Article United States1552-3365 (Electronic)'The American journal of sports medicine18326832rDepartment of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands. m.demos@erasmusmc.nleng<7@Intini, G. Andreana, S. Intini, F. E. Buhite, R. J. Bobek, L. A.2007fCalcium sulfate and platelet-rich plasma make a novel osteoinductive biomaterial for bone regeneration13 J Transl Med5BACKGROUND: With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. METHODS: First, we tested CS-Platelet in heterotopic (muscle) and orthotopic (bone) bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. RESULTS: The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS-Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. CONCLUSION: This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost-effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17343737 Journal Article England1479-5876 (Electronic)!Journal of translational medicine17343737Department of Oral Biology, University at Buffalo-109 Foster Hall, 3435 Main Street, Buffalo, NY 14214, USA. gintini@buffalo.edueng <7|Kasemkijwattana, C. Menetrey, J. Bosch, P. Somogyi, G. Moreland, M. S. Fu, F. H. Buranapanitkit, B. Watkins, S. S. Huard, J.2000CUse of growth factors to improve muscle healing after strain injury272-85Clin Orthop Relat Res370Animals Cumulative Trauma Disorders/*drug therapy/metabolism Desmin/drug effects/metabolism Disease Models, Animal Drug Evaluation, Preclinical Fibroblast Growth Factor 2/*therapeutic use Hindlimb Humans Immunohistochemistry Insulin-Like Growth Factor I/*therapeutic use Mice Mice, Inbred C57BL Muscle, Skeletal/drug effects/*injuries/metabolism Nerve Growth Factor/*therapeutic use Recombinant Proteins/therapeutic use Time Factors Vimentin/drug effects/metabolism Wound Healing/*drug effectsJan9Muscle injuries represent a large number of professional and recreational sports injuries. Muscle strains habitually occur after an eccentric contraction, which often leads to an injury located in the myotendinous junction. Treatment varies widely, depending on the severity of the trauma, but has remained limited mostly to rest, ice, compression, elevation, antiinflammatory drugs, and mobilization. The authors' research group aims to develop new biologic approaches to improve muscle healing after injuries, including muscle strains. To achieve this goal, the authors investigated several parameters that will lead to the development of new strategies to enhance muscle healing. The authors first evaluated natural muscle healing after strain injuries and showed that muscle regeneration occurs in the early phase of healing but becomes impaired with time by the development of tissue fibrosis. Several growth factors capable of improving muscle regeneration were investigated; basic fibroblast growth factor, insulin-like growth factor, and nerve growth factors were identified as substances capable of enhancing muscle regeneration and improving muscle force in the strained injured muscle. The current study should aid in the development of strategies to promote efficient muscle healing and complete recovery after strain injury.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10660723 1P60 AR44811-01/AR/United States NIAMS Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states0009-921X (Print)*Clinical orthopaedics and related research10660723KDepartment of Orthopaedic Surgery, University of Pittsburgh, PA 15261, USA.eng <7rKasemkijwattana, C. Menetrey, J. Somogyl, G. Moreland, M. S. Fu, F. H. Buranapanitkit, B. Watkins, S. C. Huard, J.1998KDevelopment of approaches to improve the healing following muscle contusion585-98Cell Transplant76Animals Contusions/physiopathology/*therapy Fibroblast Growth Factor 2/genetics *Gene Therapy Insulin-Like Growth Factor I/genetics Mice Muscle, Skeletal/*injuries/*physiology Nerve Growth Factors/genetics *Regeneration *Wound HealingNov-Dec%Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscle's ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.ehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9853587 1P60 AR44811-01/AR/United States NIAMS Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states0963-6897 (Print)Cell transplantation9853587Department of Orthopaedic Surgery, Musculoskeletal Research Center, University of Pittsburgh, and Children's Hospital of Pittsburgh, PA 15261, USA.eng<7 bMenetrey, J. Kasemkijwattana, C. Day, C. S. Bosch, P. Vogt, M. Fu, F. H. Moreland, M. S. Huard, J.2000-Growth factors improve muscle healing in vivo131-7J Bone Joint Surg Br821Animals Fibroblast Growth Factor 2/*physiology Insulin-Like Growth Factor I/*physiology Mice Muscle, Skeletal/anatomy & histology/injuries/*physiology Nerve Growth Factor/*physiology *Wound HealingJanInjury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10697329 Journal Article England0301-620X (Print)%The Journal of bone and joint surgery10697329Department of Orthopaedic Surgery, Musculoskeletal Research Centre, Children's Hospital of Pittsburgh and the University of Pittsburgh, Pennsylvania 15261, USA.eng <7 Mishra, A. Pavelko, T.2006HTreatment of chronic elbow tendinosis with buffered platelet-rich plasma1774-8Am J Sports Med3411Activities of Daily Living Adult *Blood Transfusion, Autologous Chronic Disease Cohort Studies Follow-Up Studies Humans Middle Aged Pain Measurement Patient Satisfaction Pilot Projects Platelet Transfusion/*methods Tennis Elbow/*therapy Treatment OutcomeNovJBACKGROUND: Elbow epicondylar tendinosis is a common problem that usually resolves with nonoperative treatments. When these measures fail, however, patients are interested in an alternative to surgical intervention. HYPOTHESIS: Treatment of chronic severe elbow tendinosis with buffered platelet-rich plasma will reduce pain and increase function in patients considering surgery for their problem. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: One hundred forty patients with elbow epicondylar pain were evaluated in this study. All these patients were initially given a standardized physical therapy protocol and a variety of other nonoperative treatments. Twenty of these patients had significant persistent pain for a mean of 15 months (mean, 82 of 100; range, 60-100 of 100 on a visual analog pain scale), despite these interventions. All patients were considering surgery. This cohort of patients who had failed nonoperative treatment was then given either a single percutaneous injection of platelet-rich plasma (active group, n = 15) or bupivacaine (control group, n = 5). RESULTS: Eight weeks after the treatment, the platelet-rich plasma patients noted 60% improvement in their visual analog pain scores versus 16% improvement in control patients (P =.001). Sixty percent (3 of 5) of the control subjects withdrew or sought other treatments after the 8-week period, preventing further direct analysis. Therefore, only the patients treated with platelet-rich plasma were available for continued evaluation. At 6 months, the patients treated with platelet-rich plasma noted 81% improvement in their visual analog pain scores (P =.0001). At final follow-up (mean, 25.6 months; range, 12-38 months), the platelet-rich plasma patients reported 93% reduction in pain compared with before the treatment (P <.0001). CONCLUSION: Treatment of patients with chronic elbow tendinosis with buffered platelet-rich plasma reduced pain significantly in this pilot investigation. Further evaluation of this novel treatment is warranted. Finally, platelet-rich plasma should be considered before surgical intervention.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16735582 XControlled Clinical Trial Journal Article Research Support, Non-U.S. Gov't United States0363-5465 (Print)'The American journal of sports medicine16735582Department of Orthopedic Surgery, Menlo Medical Clinic, Stanford University Medical Center, 1300 Crane Street, Menlo Park, CA 94025, USA. allan_mishra@yahoo.comengYF<7 GMishra, A. Tummala, P. King, A. Lee, B. Kraus, M. Tse, V. Jacobs, C. R.2009kBuffered Platelet-Rich Plasma Enhances Mesenchymal Stem Cell Proliferation and Chondrogenic DifferentiationTissue Eng Part C MethodsFeb 13The success of tissue engineering applications can potentially be dramatically improved with the addition of adjuncts that increase the proliferation and differentiation of progenitor or stem cells. Platelet-rich plasma (PRP) has recently emerged as a potential biologic tool to treat acute and chronic tendon disorders. The regenerative potential of PRP is based on the release of growth factors that occurs with platelet rupture. Its autologous nature gives it a significant advantage in tissue engineering applications. To test whether PRP may be useful specifically for cartilage regeneration, a cell culture experiment was devised in which mesenchymal stem cells (MSCs) were grown in control media or media enhanced with inactivated, buffered PRP. Proliferation 7 days after PRP treatment was increased: 1.041 versus 0.199 for the control media cells (p < 0.001). The messenger RNA (mRNA) level of the osteogenic marker RUNX2 was 52.84 versus 26.88 for the control group (p < 0.005). Likewise the mRNA level of the chondrogenic markers Sox-9 and aggrecan was 29.74 versus 2.29 for the control group (p < 0.001) and 21.04 versus 1.93 (p < 0.001), respectively. These results confirm that PRP enhances MSC proliferation and suggest that PRP causes chondrogenic differentiation of MSC in vitro.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19216642 Journal article1937-3384 (Print)Tissue engineering192166421 Menlo Sports Medicine , Menlo Park, California., 2 Department of Orthopaedic Surgery, Stanford University Medical Center , Stanford, California., 3 Bone and Joint R&D Center, Palo Alto Veterans Affairs Health Care Center , Palo Alto, California., 4 Department of Mechanical Engineering, Stanford University , Stanford, California., 5 Department of Biomedical Engineering, Columbia University , New York, New York.Engy<7 &Mishra, A. Woodall, J., Jr. Vieira, A.20099Treatment of tendon and muscle using platelet-rich plasma113-25Clin Sports Med281JanfTendon 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.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19064169 Journal Article United States1556-228X (Electronic)Clinics in sports medicine19064169Department of Orthopedic Surgery, Menlo Medical Clinic, Stanford University Medical Center, 1300 Crane Street, Menlo Park, CA 94025, USA. am@totaltendon.comeng<7 ?Randelli, P. S. Arrigoni, P. Cabitza, P. Volpi, P. Maffulli, N.2008SAutologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study1584-9Disabil Rehabil3020-22Aged *Arthroscopy Disability Evaluation Female Follow-Up Studies Humans *Intraoperative Care Male Pain Measurement Pilot Projects *Platelet-Rich Plasma Rotator Cuff/injuries/*surgery Thrombin/administration & dosage Transplantation, AutologousBACKGROUND 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.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18608363 Journal Article England0963-8288 (Print)Disability and rehabilitation18608363tDipartimento di Scienze Medico-Chirurgiche, Policlinico San Donato, Universita degli Studi di Milano, Milano, Italy.eng <7BSanchez, M. Anitua, E. Azofra, J. Andia, I. Padilla, S. Mujika, I.2007[Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices245-51Am J Sports Med352FAchilles Tendon/*injuries/physiology/*surgery Adult Athletic Injuries/surgery Fibrin Tissue Adhesive/*administration & dosage Follow-Up Studies Humans Male *Platelet-Rich Plasma Recovery of Function/physiology Retrospective Studies Rupture/surgery *Suture Techniques Tissue Adhesives/*administration & dosage Treatment OutcomeFeb]BACKGROUND: Platelet-rich fibrin matrices release a natural mixture of growth factors that play central roles in the complex processes of tendon healing. HYPOTHESIS: Application of autologous platelet-rich matrices during Achilles tendon surgery may promote healing and functional recovery. STUDY DESIGN: Case-control study and descriptive laboratory study; Level of evidence, 3. METHODS: Twelve athletes underwent open suture repair after complete Achilles tendon tear. Open suture repair in conjunction with a preparation rich in growth factors (PRGF) was performed in 6 athletes and retrospectively compared with a matched group that followed conventional surgical procedure. The outcomes were evaluated on the basis of range of motion, functional recovery, and complications. Achilles tendons were examined by ultrasound at 50 +/- 11 months in retrospective controls and 32 +/- 10 months in the PRGF group. In the laboratory portion of the study, PRGF treatment was characterized by the number of platelets and concentration of insulin (IGF-I), transformed (TGF-beta1), platelet-derived (PDGF-AB), vascular endothelial (VEGF), hepatocyte (HGF), and epidermal (EGF) growth factors in patients affected by musculoskeletal traumatic injuries. RESULTS: Athletes receiving PRGF recovered their range of motion earlier (7 +/- 2 weeks vs 11 +/- 3 weeks, P = .025), showed no wound complication, and took less time to take up gentle running (11 +/- 1 weeks vs 18 +/- 3 weeks, P = .042) and to resume training activities (14 +/- 0.8 weeks vs 21 +/- 3 weeks, P = .004). The cross-sectional area of the PRGF-treated tendons increased less (t = 3.44, P = .009). TGF-beta1 (74.99 +/- 32.84 ng/mL), PDGF-AB (35.62 +/- 14.57 ng/mL), VEGF (383.9 +/- 374.9 pg/mL), EGF (481.5 +/- 187.5 pg/mL), and HGF (593.87 +/- 155.76 pg/mL) significantly correlated with the number of platelets (677 +/- 217 platelets/microL, P < .05). CONCLUSION: The operative management of tendons combined with the application of autologous PRGF may present new possibilities for enhanced healing and functional recovery. This needs to be evaluated in a randomized clinical trial.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17099241 PComparative Study Journal Article Research Support, Non-U.S. Gov't United States0363-5465 (Print)'The American journal of sports medicine17099241JArthroscopic Surgery Unit, USP-La Esperanza Clinic, Basque Country, Spain.eng<7RSanchez, M. Azofra, J. Anitua, E. Andia, I. Padilla, S. Santisteban, J. Mujika, I.2003UPlasma rich in growth factors to treat an articular cartilage avulsion: a case report1648-52Med Sci Sports Exerc3510Adolescent Arthroscopy Blood Transfusion, Autologous Cartilage, Articular/*injuries/*surgery Growth Substances/blood/*therapeutic use Humans Knee Injuries/*surgery/*therapy Male Soccer Wound HealingOctINTRODUCTION: The application of an autologous plasma rich in growth factors is beneficial in restoring connective tissues, as shown by clinical evidence in oral surgery and more recently in arthroscopic anterior cruciate ligament reconstruction and two cases of ruptured Achilles tendon in professional athletes. This is attributed to the slow delivery of growth factors from harvested platelets that have been activated by endogenous thrombin promoted by the addition of calcium chloride. PURPOSE: This case report describes a new application of this therapy in the arthroscopic treatment of a large, nontraumatic avulsion of articular cartilage in the knee of an adolescent soccer player. METHODS: After arthroscopic reattachment of the large (>2 cm) loose chondral body in its crater in the medial femoral condyle, autologous plasma rich in growth factors was injected into the area between the crater and the fixed fragment. RESULTS AND CONCLUSION: Despite the extremely poor prognosis of the case, complete articular cartilage healing was considerably accelerated, and the functional outcome was excellent, allowing a rapid resumption of symptom-free athletic activity. This technique opens new perspectives for human tissue regeneration.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14523300 *Case Reports Journal Article United States0195-9131 (Print)+Medicine and science in sports and exercise14523300[Arthroscopic Surgery Unit, USP-La Esperanza Clinic, Vitoria-Gasteiz, Basque Country, SPAIN.eng<7ESariguney, Y. Yavuzer, R. Elmas, C. Yenicesu, I. Bolay, H. Atabay, K.2008?Effect of platelet-rich plasma on peripheral nerve regeneration159-67J Reconstr Microsurg243Animals Electromyography Female Microsurgery/methods Models, Animal Muscle, Skeletal/pathology Myelin Sheath/ultrastructure *Nerve Regeneration *Platelet-Rich Plasma Rats Rats, Wistar Sciatic Nerve/injuries/*physiology/*surgery SuturesAprActivated platelets release various growth factors, some of which are recognized to improve nerve regeneration. This study evaluated the effect of platelet-rich plasma (PRP) in end-to-end neurorrhaphy. A total of 45 Wistar rats were used, with the initial five used for PRP preparation. The right hind limbs were used as experimental, with the left as control. The animals were treated in five groups. Group A (n = 4): The right sciatic nerve was dissected only from the sciatic notch to the bifurcation. In all other groups, the nerve was sharply transected and repaired with: group B (n = 8): two sutures; group C (n = 8): six sutures; group D (n = 10): two sutures and PRP; and group E (n = 10): six sutures and PRP. Groups D and E were compared with groups B and C, respectively. Group E had a shorter latency time in electromyography ( P < 0.01) and a thicker myelin layer in the histological evaluation ( P < 0.003) in comparison with group C. These positive effects of PRP were not detected in the nerves were repaired with two sutures. In this animal model, the application of PRP to the repair site helped to improve remyelinization of the sciatic nerve in rats when the epineural repair was done with six sutures.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18452111 Journal Article United States0743-684X (Print)&Journal of reconstructive microsurgery18452111qDepartment of Plastic, Reconstructive and Aesthetic Surgery, Gazi University Faculty of Medicine, Ankara, Turkey.eng <7\Sato, K. Li, Y. Foster, W. Fukushima, K. Badlani, N. Adachi, N. Usas, A. Fu, F. H. Huard, J.2003cImprovement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis365-72 Muscle Nerve283SAnimals Disease Models, Animal Drug Therapy, Combination Extracellular Matrix Proteins Fibrosis/*drug therapy/etiology/*prevention & control Insulin-Like Growth Factor I/*pharmacology/therapeutic use Mice Muscle Contraction/drug effects/physiology Muscle Fibers/cytology/drug effects/metabolism Muscle Fibers, Fast-Twitch/cytology/drug effects/metabolism Muscle, Skeletal/*drug effects/*injuries/physiopathology Proteoglycans/*pharmacology/therapeutic use Recovery of Function/drug effects/physiology Regeneration/*drug effects/physiology Treatment Outcome Wound Healing/*drug effects/physiologySepSkeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor-1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12929198 R01 AR47973-01/AR/United States NIAMS Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States0148-639X (Print)Muscle & nerve12929198yGrowth and Development Laboratory, Department of Orthopaedic Surgery, Children's Hospital, Pittsburgh, Pennsylvania, USA.eng B|7oSchnabel, L. V. Mohammed, H. O. Miller, B. J. McDermott, W. G. Jacobson, M. S. Santangelo, K. S. Fortier, L. A.2007oPlatelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons230-40 J Orthop Res252$Animals Collagen/genetics/metabolism DNA/genetics/metabolism Dose-Response Relationship, Drug Extracellular Matrix Proteins/genetics/metabolism Gene Expression Regulation/*physiology Glycoproteins/genetics/metabolism Horses Insulin-Like Growth Factor I/genetics/metabolism Metabolism/genetics/*physiology Platelet-Derived Growth Factor/genetics/metabolism *Platelet-Rich Plasma/physiology RNA, Messenger/genetics/metabolism Tendinopathy/drug therapy Tendons/*metabolism Tissue Culture Techniques Transforming Growth Factor beta1/genetics/metabolismFebPlatelet 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.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17106885 wJournal Article Research Support, Non-U.S. Gov't United States official publication of the Orthopaedic Research Society0736-0266 (Print)17106885]Department of Clinical Sciences, VMC C3-181, Cornell University, Ithaca, New York 14853, USA.eng x<7Virchenko, O. Aspenberg, P.2006How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation806-12 Acta Orthop775aAchilles Tendon/injuries/physiology Animals Biomechanics Blood Platelets/*physiology Botulinum Toxin Type A/administration & dosage Neuromuscular Agents/administration & dosage Physical Stimulation Rats Rats, Sprague-Dawley Regeneration/*physiology Rupture Tendon Injuries/physiopathology/*therapy Tensile Strength Time Factors Wound Healing/*physiologyOctBACKGROUND: Mechanical stimulation improves the repair of ruptured tendons. Injection of a platelet concentrate (platelet-rich plasma, PRP) can also improve repair in several animal models. In a rat Achilles tendon transection model, 1 postoperative injection resulted in increased strength after 4 weeks. Considering the short half-lives of factors released by platelets, this very late effect calls for an explanation. METHODS: We studied the effects of platelets on Achilles tendon regenerates in rats 3, 5 and 14 days after transection. The tendons were either unloaded by Botulinum toxin A (Botox) injections into the calf muscles, or mechanically stimulated in activity cages. No Botox injections and ordinary cages, respectively, served as controls. Repair was evaluated by tensile testing. RESULTS: At 14 days, unloading (with Botox) abolished any effect of the platelets and reduced the mechanical properties of the repair tissue to less than half of normal. Thus, some mechanical stimulation is a prerequisite for the effect of platelets at 14 days. Without Botox, both activity and platelets increased repair independently of each other. However, at 3 and 5 days, platelets improved the mechanical properties in Botox-treated rats. INTERPRETATION: Platelets influence only the early phases of regeneration, but this allows mechanical stimulation to start driving neo-tendon development at an earlier time point, which kept it constantly ahead of the controls.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17068715 7Journal Article Research Support, Non-U.S. Gov't Sweden1745-3674 (Print)Acta orthopaedica17068715Orthopaedics and Sports Medicine, Department of Neuroscience and Locomotion, Linkoping University, Linkoping, SE-581 85, Sweden.engc|7]Wehling, P. Moser, C. Frisbie, D. McIlwraith, C. W. Kawcak, C. E. Krauspe, R. Reinecke, J. A.2007[Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy323-32BioDrugs215Animals Blood Transfusion, Autologous/*methods Bone Diseases/*therapy Humans Injections, Intra-Articular Interleukin-1 Receptor Accessory Protein/administration & dosage/chemistry/therapeutic use Muscular Diseases/therapy Serum/*chemistry/immunologyThe common strategies for the treatment of patients with orthopedic diseases do not address the underlying pathogenesis. Several biologically based, local therapies aiming to influence the cytokine imbalance are either in development or in the initial stages of clinical use. A method based on exposure of blood leukocytes to pyrogen-free surfaces (e.g. glass spheres) elicits an accumulation of anti-inflammatory cytokines, including interleukin-1 receptor antagonist, and several growth factors, including insulin-like growth factor-1, platelet-derived growth factor, and transforming growth factor-beta(1), in the liquid blood phase. Based on these observations, a new therapy using cell-free, autologous conditioned serum (ACS) from the incubation of whole blood with glass spheres was developed. The injection of ACS into affected tissue(s) has shown clinical effectiveness and safety in animal models and studies, as well as in human clinical studies, for the treatment of osteoarthritis, lumbar stenosis, disc prolapse, and muscle injuries.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17896838 Journal Article Research Support, Non-U.S. Gov't Review New Zealand clinical immunotherapeutics, biopharmaceuticals and gene therapy1173-8804 (Print)17896838HCentre for Molecular Orthopaedics, Dusseldorf, Germany. p.wehling@gmx.deeng<7>Woodall, J., Jr. Tucci, M. Mishra, A. Asfour, A. Benghuzzi, H.2008YCellular effects of platelet rich plasmainterleukin1 release from prp treated macrophages489-94Biomed Sci Instrum44The therapeutic use of Platelet Rich Plasma (PRP) as a biological tool to enhance soft tissue and bone healing has recently yielded encouraging results in many areas of clinical medicine. PRP is a specific portion of whole blood that contains a high concentration of platelets. The local treatment of bone and soft tissue injuries with this autologous blood product has become increasingly common in recent years. There is still little known about the mechanism by which PRP acts at the cellular level. The macrophage cell has been shown to be critical in the healing of tissues. In this study the macrophage release of a specific pro-inflammatory factor, interleukin-1 (IL-1), was evaluated in macrophage cells activated and treated with platelets as compared to control macrophages in culture. The results show that platelets caused an initial suppression of IL-1 release from activated macrophage compared to controls. The initial suppression was followed by an increase in IL-1 release at day seven over control and activated macrophages that had ceased release of IL-1 at day seven. The initial suppression of the inflammatory response to activation during days 1, 2 and 3 could have broad implications in the explanation of a mechanism by which PRP acts. If PRP can truly be used as a transient anti-inflammatory agent that initially suppresses inflammation and then stimulates a late healing response, then indications for use of PRP may expand beyond the current scope of treatment.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19141963 Journal Article United States0067-8856 (Print)#Biomedical sciences instrumentation19141963Department of Orthopedic Surgery and Rehabilitation, University of Mississippi Medical Center, Jackson, MS, 39216, USA. jwoodall@orthopedics.umsmed.edu.eng ,<7SWright-Carpenter, T. Klein, P. Schaferhoff, P. Appell, H. J. Mir, L. M. Wehling, P.2004Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains588-93Int J Sports Med258Athletic Injuries/*therapy Case-Control Studies Enzyme-Linked Immunosorbent Assay Growth Substances/*biosynthesis/blood Humans Male Muscle, Skeletal/*injuries Pilot Projects Stimulation, Chemical Wound Healing/*physiologyNovMuscle injuries represent a major part of sports injuries and are a challenging problem in traumatology. Strain injuries are the most common muscle injuries after contusions. These injuries can lead to significant pain and disability causing time to be lost to training and competition. Despite the frequency of strain injuries the treatment available is limited and is generally not sufficient to enhance muscle regeneration efficiently when fast resumption of sport activity is a primary target. A number of growth factors play a specific role in regeneration and it has been proven that a previously described method of physically and chemically stimulating whole blood (to produce autologous conditioned serum) induces concentration increases in FGF-2, HGF, and TGF-beta1. A preliminary study was conducted on muscle strain injuries in professional sportsmen receiving either: 1. autologous conditioned serum (ACS) or 2. Actovegin/Traumeel treatment as control. Assessment of recovery from injury was done by: 1. sport professional's ability to participate to 100 % under competition conditions in their respective sport and 2. MRI analysis. A significant difference in the recovery time from injury was demonstrated: 16.6 +/- 0.9 in the ACS treated instead of 22.3 +/- 1.2 (mean +/- SEM) days in the Actovegin/Traumeel control group (p = 0.001). MRI analysis supported the observed acceleration of the lesion recovery time. We conclude that ACS injection is a promising approach to reduce the time to recovery from muscle injury.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15532001 8Journal Article Research Support, Non-U.S. Gov't Germany0172-4622 (Print)(International journal of sports medicine15532001:UMR 8121 CNRS, Institut Gustave-Roussy, Villejuif, France.eng D<7OWright-Carpenter, T. Opolon, P. Appell, H. J. Meijer, H. Wehling, P. Mir, L. M.2004Treatment of muscle injuries by local administration of autologous conditioned serum: animal experiments using a muscle contusion model582-7Int J Sports Med258Animals Contusions/*therapy Enzyme-Linked Immunosorbent Assay Fibroblast Growth Factor 2/*biosynthesis/blood Injections, Intramuscular Mice Mice, Inbred C57BL Models, Animal Muscle Fibers/physiology Muscle, Skeletal/*injuries Regeneration/physiology Satellite Cells, Skeletal Muscle/metabolism Stimulation, Chemical Transforming Growth Factor beta/*biosynthesis/blood Wound Healing/*physiologyNovcMuscle contusions represent a major part of sports injuries. The suggested treatments are generally sufficient to support muscle healing, but require a relatively long period of time. Given that autologous blood products are safe treatments, we have used a technique which stimulates the release of certain growth factors in the autologous conditioned serum (ACS). Those growth factors are known to improve the proliferative activity of myogenic precursor cells. Mice were subjected to an experimental contusion injury to their gastrocnemius muscle; one group received local injections of ACS at 2 hrs, 24 hrs, and 48 hrs after injury, a control group received saline injections. The histology results showed that satellite cell activation at 30/48 hrs post injury was accelerated and the diameter of the regenerating myofibers was increased compared to the controls within the first week after injury. ELISA results on the ACS have shown that the elevations in FGF-2 (460 %) and TGF-beta1 (82 %) could be partly responsible for the accelerating effects on regeneration due to proliferative and chemotactic properties. We conclude that ACS injection is a promising approach to reduce the time of recovery from muscle injury. In terms of clinical targets, this new approach could be used in the treatment of sports injuries and may also be interesting in postoperative situations.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15532000 AIn Vitro Journal Article Research Support, Non-U.S. Gov't Germany0172-4622 (Print)(International journal of sports medicine15532000:UMR 8121 CNRS, Institut Gustave-Roussy, Villejuif, France.eng |<7pYuasa, T. Kakuhata, R. Kishi, K. Obata, T. Shinohara, Y. Bando, Y. Izumi, K. Kajiura, F. Matsumoto, M. Ebina, Y.2004Platelet-derived growth factor stimulates glucose transport in skeletal muscles of transgenic mice specifically expressing platelet-derived growth factor receptor in the muscle, but it does not affect blood glucose levels2776-86Diabetes5311oAnimals Biological Transport/drug effects Blood Glucose/drug effects/*metabolism Glucose/*metabolism Heart/physiology Insulin/pharmacology Mice Mice, Transgenic Muscle, Skeletal/physiology Platelet-Derived Growth Factor/*pharmacology Receptor, Platelet-Derived Growth Factor beta/drug effects/genetics/*physiology Recombinant Proteins/pharmacology Signal TransductionNovInsulin stimulates the disposal of blood glucose into skeletal muscle and adipose tissues by the translocation of GLUT4 from intracellular pools to the plasma membrane, and consequently the concentration of blood glucose levels decreases rapidly in vivo. Phosphatidylinositol (PI) 3-kinase and Akt play a pivotal role in the stimulation of glucose transport by insulin, but detailed mechanisms are unknown. We and others reported that not only insulin but also platelet-derived growth factor (PDGF) and epidermal growth factor facilitate glucose uptake through GLUT4 translocation by activation of PI 3-kinase and Akt in cultured cells. However, opposite results were also reported. We generated transgenic mice that specifically express the PDGF receptor in skeletal muscle. In these mice, PDGF stimulated glucose transport into skeletal muscle in vitro and in vivo. Thus, PDGF apparently shares with insulin some of the signaling molecules needed for the stimulation of glucose transport. The degree of glucose uptake in vivo reached approximately 60% of that by insulin injection in skeletal muscle, but blood glucose levels were not decreased by PDGF in these mice. Therefore, PDGF-induced disposal of blood glucose into skeletal muscle is insufficient for rapid decrease of blood glucose levels.fhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15504957 >Journal Article Research Support, Non-U.S. Gov't United States0012-1797 (Print)Diabetes15504957Division of Molecular Genetics, Institute for Enzyme Research, the University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.engPKFh:I/**refs.FRM 0B< !// !HPRIMARYyearIndex 6ByP/) idreference_type text_stylesauthoryear title pages secondary_title volume numbernumber_of_volumessecondary_authorplace_published publishersubsidiary_authoredition keywords type_of_workdate2)  abstractlabelurltertiary_titletertiary_author notes isbn custom_1 custom_2 custom_3 custom_4alternate_titleaccession_number call_number short_title custom_5 custom_6sectionoriginal_publicationH) reprint_editionreviewed_itemauthor_addressimagecaption custom_7 electronic_resource_number link_to_pdf translated_author translated_titlename_of_databasedatabase_providerresearch_notes language access_datelast_modified_date !! 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