Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering
Abstract
Using the modified preplate technique, we have isolated a population of early myogenic progenitor cells from postnatal skeletal muscle that display stem cell characteristics. We have shown that these "muscle-derived stem cells" (MDSCs) can differentiate toward myogenic, osteogenic, chondrogenic, neurogenic, and hematopoietic lineages. Specifically, MDSCs cultured in chondrogenic medium can undergo chondrogenic differentiation in vitro, and MDSCs delivered to osteochondral defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have observed that bone morphogenetic protein 4 (BMP4) promotes chondrogenic differentiation of MDSCs in vitro and in vivo and that this cytokine can trigger chondrogenic differentiation of other populations of muscle-derived cells, including myoblasts (late myogenic progenitor cells) and fibroblasts. The proposed project will investigate the use of these populations of muscle-derived cells as novel cell sources for articular cartilage repair in osteochondral defects created in nude rats. We will investigate the in vitro chondrogenic potential of various populations of mouse muscle-derived cells (fibroblastic cells and early and late myogenic progenitor cells) expressing BMP4 and determine the regenerative capacity of these cells after implantation in rat articular cartilage defects. We then will explore the relative contributions of these muscle-derived cells' long-term proliferation, survival, and self renewal to their regenerative capacity after transplantation into the cartilage defects . Next, we will determine the contributions of angiogenesis and scar tissue formation to the regenerative capacity of the muscle-derived cells and to the overall quality of the cartilage generated within the treated osteochondral defects.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2010
- Accession Number
- ADA536482
Entities
People
- Johnny Huard