Chondrogenic differentiation of human mesenchymal stem cell aggregates via controlled release of TGF-beta1 from incorporated polymer microspheres

J Biomed Mater Res A. 2010 Mar 1;92(3):1139-44. doi: 10.1002/jbm.a.32440.


Aggregate culture is a useful method for inducing chondrogenic differentiation of human mesenchymal stem cells (hMSC) in a three-dimensional in vitro culture environment. Conventional aggregate culture, however, typically requires repeated growth factor supplementation during media changes, which is both expensive and time-intensive. In addition, homogenous cell differentiation is limited by the diffusion of chondrogenic growth factor from the culture medium into the aggregate and peripheral cell consumption of the growth factor. We have engineered a technology to incorporate growth factor-loaded polymer microspheres within hMSC aggregates themselves. Here, we report on the system's capacity to induce chondrogenesis via sustained delivery of transforming growth factor-beta1 (TGF-beta1). Cartilage formation after 3 weeks in the absence of externally supplied growth factor approached that of aggregates cultured by conventional methods. Chondrogenesis in the central region of the aggregates is enabled at TGF-beta1 levels much lower than those required by conventional culture using exogenously supplied TGF-beta1, which is likely a result of the system's ability to overcome limitations of growth factor diffusion from cell culture media surrounding the exterior of the aggregates. Importantly, the inclusion of growth factor-releasing polymer microspheres in hMSC aggregates could enable in vivo chondrogenesis for cartilage tissue engineering applications without extensive in vitro culture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Chondrocytes / cytology*
  • Culture Media
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Microscopy, Electron, Scanning
  • Microspheres*
  • Transforming Growth Factor beta1 / metabolism*


  • Culture Media
  • Transforming Growth Factor beta1