Chondrogenesis and integration of mesenchymal stem cells within an in vitro cartilage defect repair model.
Integration of repair tissue is a key indicator of the long-term success of cell-based therapies for cartilage repair. The objective of this study was to compare the in vitro chondrogenic differentiation and integration of agarose hydrogels seeded with either chondrocytes or bone marrow-derived mesenchymal stem cells (MSCs) in defects created in cartilage explants. Chondrocytes and MSCs were isolated from porcine donors, suspended in 2% agarose and then injected into cylindrical defects within the explants. These constructs were maintained in a chemically defined medium supplemented with 10 ng/mL of TGF-beta3. Cartilage integration was assessed by histology and mechanical push-out tests. After 6 weeks in culture, chondrocyte-seeded constructs demonstrated a higher integration strength (64.4 +/- 8.3 kPa) compared to MSC-seeded constructs (22.7 +/- 5.9 kPa). Glycosaminoglycan (GAG) (1.27 +/- 0.3 vs. 0.19 +/- 0.03 kPa) and collagen (0.31 +/- 0.08 vs. 0.09 +/- 0.01 kPa) accumulation in chondrocyte-seeded constructs was greater than that measured in the MSC-seeded group. The GAG, collagen, and DNA content of both chondrocyte- and MSC-seeded hydrogels cultured in cartilage explants was significantly lower than control constructs cultured in free swelling conditions. The results of this study suggest that the explant model may constitute a more rigorous in vitro test to assess MSC therapies for cartilage defect repair.
Vinardell
T
T
Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
Thorpe
S D
SD
Buckley
C T
CT
Kelly
D J
DJ
D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries* / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D020219:Chondrogenesis; D066298:In Vitro Techniques; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D013552:Swine