Chondrogenic, hypertrophic, and osteochondral differentiation of human mesenchymal stem cells on three‐dimensionally woven scaffolds
Name
nihms-1030714.pdf
Description
Accepted version
Size
2.85 MB
Format
Adobe PDF
Checksum (MD5)
c44d38e6ce784744331c8ae1e22a0e71
Author(s)
Larson, Benjamin
Yu, Sarah N.
Park, Hyoungshin
Wu, Patrick B.
Langer, Robert S
Freed, Lisa E
Date Issued
August 2019
Journal
Journal of Tissue Engineering and Regenerative Medicine
Publisher
Wiley
Citation
Larson, Benjamin L. et al. “Chondrogenic, hypertrophic, and osteochondral differentiation of human mesenchymal stem cells on three‐dimensionally woven scaffolds.” Journal of Tissue Engineering and Regenerative Medicine, 13, 8 (August 2019): 1453–1465 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
The development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remains an important challenge for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSCs) in large, three-dimensionally woven poly(ε-caprolactone; PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations—PCL alone, PCL-bone, “point-of-care” seeded MSC-PCL-bone, and chondrogenically precultured Ch-MSC-PCL-bone constructs—were implanted in a dorsal, ectopic pouch in a nude rat. After 8 weeks, only cells in the Ch-MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, although both tissue profiles were present, constructs that had been chondrogenically precultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1002/TERM.2899
