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Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

Nature Materials volume 7, pages 816–823 (2008)Cite this article

Abstract

Cell–matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.

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Figure 1: Small-molecule incorporation alters hMSC protein expression on PEG hydrogels.
Figure 2: Small-molecule incorporation alters hMSC gene expression on PEG hydrogels.
Figure 3: hMSC morphology is altered in response to small-molecule incorporation into PEG hydrogels.
Figure 4: Encapsulation of hMSCs in phosphate- and t-butyl-functionalized PEG hydrogels induces MSC osteogenesis and adipogenesis, respectively.

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Acknowledgements

This work was supported by a grant from the National Institute of Health (DE016523). The authors would like to thank C. Bowman and H. Sikes for use of and assistance with the ChipWriter, K. Rowlen and E. Dawson for use of and help with the ChipReader, E. Kovacs for technical assistance associated with in situ hybridization and J. McCormick and S. George for assistance with the X-ray photoelectron spectroscopy studies. Fellowship assistance to D.S.W.B. was awarded by the US Department of Education’s Graduate Assistantships in Areas of National Need program and the National Science Foundation Graduate Research Fellowship program.

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering, University of Colorado, 424 UCB ECCH 111, Boulder, Colorado 80309, USA

    Danielle S. W. Benoit, Michael P. Schwartz, Andrew R. Durney & Kristi S. Anseth

  2. Howard Hughes Medical Institute, University of Colorado, 424 UCB ECCH 111, Boulder, Colorado 80309, USA

    Michael P. Schwartz & Kristi S. Anseth

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  1. Danielle S. W. Benoit
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Contributions

D.S.W.B. and K.S.A. came up with the concept, D.S.W.B., M.P.S. and K.S.A. designed the experiments, D.S.W.B. and A.R.D. carried out the experiments and D.S.W.B., M.P.S. and K.S.A. wrote the paper.

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Correspondence to Kristi S. Anseth.

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Benoit, D., Schwartz, M., Durney, A. et al. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nature Mater 7, 816–823 (2008). https://doi.org/10.1038/nmat2269

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