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Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels

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Abstract

Bone-marrow-derived mesenchymal stem cells (MSCs) are candidates for regeneration applications in musculoskeletal tissue such as cartilage and bone. Various soluble factors in the form of growth factors and cytokines have been widely studied for directing the chondrogenic and osteogenic differentiation of MSCs, but little is known about the way that the composition of extracellular matrix (ECM) components in three-dimensional microenvironments plays a role in regulating the differentiation of MSCs. To define whether ECM components influence the regulation of osteogenic and chondrogenic differentiation by MSCs, we encapsulated MSCs in poly-(ethylene glycol)-based (PEG-based) hydrogels containing exogenous type I collagen, type II collagen, or hyaluronic acids (HA) and cultured them for up to 6 weeks in chondrogenic medium containing transforming growth factor-β1 (10 ng/ml) or osteogenic medium. Actin cytoskeleton organization and cellular morphology were strongly dependent on which ECM components were added to the PEG-based hydrogels. Additionally, chondrogenic differentiation of MSCs was marginally enhanced in collagen-matrix-based hydrogels, whereas osteogenic differentiation, as measured by calcium accumulation, was induced in HA-containing hydrogels. Thus, the microenvironments created by exogenous ECM components seem to modulate the fate of MSC differentiation.

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Acknowledgments

The authors are grateful to Dr. Zijun Zhang (St. Louis University, Department of Orthopedic Surgery) for critical review and to Dr. Rober E. Allen (Johns Hopkins University, Department of Biomedical Engineering) for access to the Instron Universal Testing Machine.

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Authors and Affiliations

  1. Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins School of Medicine, 400 N Broadway, Smith 5035, Baltimore, MD, USA

    Nathaniel S. Hwang, Hanwei Li & Jennifer Elisseeff

  2. Department of Bioengineering, University of California at San Diego, La Jolla, CA 92092, USA

    Shyni Varghese

  3. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

    Nathaniel S. Hwang

Authors
  1. Nathaniel S. Hwang
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  2. Shyni Varghese
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  3. Hanwei Li
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  4. Jennifer Elisseeff
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Corresponding author

Correspondence to Jennifer Elisseeff.

Additional information

This study was supported by the National Institutes of Health (R01 AR054005-01 and R01DE16887) and the Arthritis Foundation.

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Hwang, N.S., Varghese, S., Li, H. et al. Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels. Cell Tissue Res 344, 499–509 (2011). https://doi.org/10.1007/s00441-011-1153-2

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  • DOI: https://doi.org/10.1007/s00441-011-1153-2

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