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

Summary 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) combine...

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Published in:	Osteoarthritis and cartilage Vol. 21; no. 1; pp. 175 - 185
Main Authors:	Mifune, Y, Matsumoto, T, Takayama, K, Ota, S, Li, H, Meszaros, L.B, Usas, A, Nagamune, K, Gharaibeh, B, Fu, F.H, Huard, J
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-01-2013
Subjects:	Animals Apoptosis - drug effects Bone Morphogenetic Protein 4 - metabolism Cartilage, Articular - drug effects Cartilage, Articular - metabolism Chondrocytes - metabolism Collagen Type II - biosynthesis Female Muscle derived stem cells Osteoarthritis Osteoarthritis, Knee - drug therapy Platelet-Rich Plasma Rats Rats, Nude Rheumatology Stem Cell Transplantation Stem Cells - drug effects Stem Cells - metabolism Stifle Vascular Endothelial Growth Factor Receptor-1 - metabolism Muscle derived stem cells Osteoarthritis Platelet-rich plasma
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Summary:	Summary 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1063-4584 1522-9653
DOI:	10.1016/j.joca.2012.09.018