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The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair

Mifune, Y and Matsumoto, T and Takayama, K and Ota, S and Li, H and Meszaros, LB and Usas, A and Nagamune, K and Gharaibeh, B and Fu, FH and Huard, J (2013) The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthritis and Cartilage, 21 (1). 175 - 185. ISSN 1063-4584

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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. © 2012 Osteoarthritis Research Society International.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Mifune, Y
Matsumoto, T
Takayama, K
Ota, S
Li, Hhol24@pitt.eduHOL24
Meszaros, LB
Usas, A
Nagamune, K
Gharaibeh, Bburhan@pitt.eduBURHAN0000-0002-5947-1232
Fu, FHffu@pitt.eduFFU
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 January 2013
Date Type: Publication
Journal or Publication Title: Osteoarthritis and Cartilage
Volume: 21
Number: 1
Page Range: 175 - 185
DOI or Unique Handle: 10.1016/j.joca.2012.09.018
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 1063-4584
PubMed ID: 23041435
Date Deposited: 31 Mar 2014 15:00
Last Modified: 03 Jan 2022 12:55


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