Spatiotemporal control of proliferation and differentiation of bone marrow-derived mesenchymal stem cells recruited using collagen hydrogel for repair of articular cartilage defects

Articular cartilage has a poor healing capacity, and cartilage regeneration is not always warranted to achieve healing. On the other hand, collagen scaffolds have been shown to support regeneration of articular cartilage defects in animal models, whereas bone morphogenetic protein-2 (BMP-2) is known to cause chondrogenic differentiation of marrow-derived mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the effectiveness of intraarticular administration of BMP-2 into bone marrow-derived MSCs recruited to defects using original collagen hydrogel in rabbits at various time points. Full-thickness defects were created in both knees, then collagen hydrogels were transplanted, and BMP-2 was supplied for 1-week periods, as follows. BMP-2 was administered immediately after the operation for 1 week (BMP0-1 group), and BMP-2 was administered between weeks 1 and 2 after the operation (BMP1-2 group). BMP2 was administered between weeks 2 and 3 (BMP2-3 group). Specimens were then obtained, and bromodeoxyuridine (BrdU)-positive cells were enumerated and histologic grading was also performed. In addition, the gene expression analysis was performed using quantitative real-time reverse transcription polymerase chain reaction (RTPCR) assays. Enumeration of BrdU-positive cells showed a significant increase in the BMP0-1 group compared with the other groups. Similarly, histologic scores in the BMP0-1 group were superior for up to 8 weeks. Finally, RT-PCR findings revealed that immediate BMP-2 administration enhanced chondrogenic differentiation. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 98B: 360-368, 2011.