A single day of TGF-?1 exposure activates chondrogenic and hypertrophic differentiation pathways in bone marrow-derived stromal cells.

ABSTRACT: Virtually all bone marrow-derived stromal cell (BMSC) chondrogenic induction cultures include greater than 2 weeks exposure to transforming growth factor-? (TGF-?), but fail to generate cartilage-like tissue suitable for joint repair. Herein we used a micro-pellet model (5?×?10³ BMSC each) to determine the duration of TGF-?1 exposure required to initiate differentiation machinery, and to characterize the role of intrinsic programming. We found that a single day of TGF-?1 exposure was sufficient to trigger BMSC chondrogenic differentiation and tissue formation, similar to 21 days of TGF-?1 exposure. Despite cessation of TGF-?1 exposure following 24?hours, intrinsic programming mediated further chondrogenic and hypertrophic BMSC differentiation. These important behaviors are obfuscated by diffusion gradients and heterogeneity in commonly used macro-pellet models (2?×?10⁵ BMSC each). Use of more homogenous micro-pellet models will enable identification of the critical differentiation cues required, likely in the first 24-hours, to generate high quality cartilage-like tissue from BMSC.

SUBMITTER: Futrega K 

PROVIDER: S-EPMC7782775 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature