title: The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair.
abstract: OBJECTIVE
  Platelet-rich plasma (PRP) is reported to promote collagen synthesis and cell proliferation as well as enhance cartilage repair. Our previous study revealed that the intracapsular injection of muscle derived stem cells (MDSCs) expressing bone morphogenetic protein 4 (BMP-4) combined with soluble Flt-1 (sFlt1) was effective for repairing articular cartilage (AC) after osteoarthritis (OA) induction. The current study was undertaken to investigate whether PRP could further enhance the therapeutic effect of MDSC therapy for the OA treatment.
  
  
  METHODS
  MDSCs expressing BMP-4 and sFlt1 were mixed with PRP and injected into the knees of immunodeficient rats with chemically induced OA. Histological assessments were performed 4 and 12 weeks after cell transplantation. Moreover, to elucidate the repair mechanisms, we performed in vitro assays to assess cell proliferation, adhesion, migration and mixed pellet co-culture of MDSCs and OA chondrocytes.
  
  
  RESULTS
  The addition of PRP to MDSCs expressing BMP-4 and sFlt1 significantly improved AC repair histologically at week 4 compared to MDSCs expressing BMP-4 and sFlt1 alone. Higher numbers of cells producing type II collagen and lower levels of chondrocyte apoptosis were observed by MDSCs expressing BMP-4 and sFlt1 and mixed with PRP. In the in vitro experiments, the addition of PRP promoted proliferation, adhesion and migration of the MDSCs. During chondrogenic pellet culture, PRP tended to increase the number of type II collagen producing cells and in contrast to the in vivo data, it increased cell apoptosis.
  
  
  CONCLUSIONS
  Our findings indicate that PRP can promote the therapeutic potential of MDSCs expressing BMP-4 and sFlt1 for AC repair (4 weeks post-treatment) by promoting collagen synthesis, suppressing chondrocyte apoptosis and finally by enhancing the integration of the transplanted cells in the repair process.
authors.affiliation: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mifune
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Takayama
authors.forename: S
authors.initials: S
authors.lastname: Ota
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: L B
authors.initials: LB
authors.lastname: Meszaros
authors.forename: A
authors.initials: A
authors.lastname: Usas
authors.forename: K
authors.initials: K
authors.lastname: Nagamune
authors.forename: B
authors.initials: B
authors.lastname: Gharaibeh
authors.forename: F H
authors.initials: FH
authors.lastname: Fu
authors.forename: J
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D024043:Collagen Type II / Q000096:biosynthesis; D005260:Female; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D053657:Platelet-Rich Plasma; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013264:Stifle; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D055415:Bone Morphogenetic Protein 4; D024043:Collagen Type II; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1