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Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells

Nature Biotechnology volume 28, pages 1123–1128 (2010)Cite this article

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Abstract

Surprisingly little is known about the effects of the physical microenvironment on hemopoietic stem and progenitor cells. To explore the physical effects of matrix elasticity on well-characterized primitive hemopoietic cells, we made use of a uniquely elastic biomaterial, tropoelastin. Culturing mouse or human hemopoietic cells on a tropoelastin substrate led to a two- to threefold expansion of undifferentiated cells, including progenitors and mouse stem cells. Treatment with cytokines in the presence of tropoelastin had an additive effect on this expansion. These biological effects required substrate elasticity, as neither truncated nor cross-linked tropoelastin reproduced the phenomenon, and inhibition of mechanotransduction abrogated the effects. Our data suggest that substrate elasticity and tensegrity are important mechanisms influencing hemopoietic stem and progenitor cell subsets and could be exploited to facilitate cell culture.

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Figure 1: Tropoelastin increased mouse hemopoietic stem and progenitor cells.
Figure 2: Tropoelastin increased human hemopoietic progenitor cells.
Figure 3: Effect of tropoelastin truncations and cross-linking on the ability of mouse hemopoietic cells to respond to tropoelastin.
Figure 4: QCM-D analysis of collagen, fibronectin, tropoelastin and ELN27-540 binding to oxidized polystyrene, and the effect of myosin II heavy chain and myosin light chain kinase inhibitors on the ability of mouse hemopoietic cells to respond to tropoelastin.

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  • 27 April 2011

    In the version of this article initially published, the description of the grade of tropoelastin used was incorrect. The correct description is “research and development (R&D)-grade tropoelastin (Elastagen Pty. Ltd.).” The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank D. Vignali for scientific discussion. J.H. received grant support from the Cancer Institute of New South Wales, A.S.W. from the Australian Research Council and National Health and Medical Research Council, A.F.O. received support from the US National Institutes of Health and J.E.J.R. from the National Health and Medical Research Council and the Cell and Gene Trust, Cure The Future.

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Authors and Affiliations

  1. Gene & Stem Cell Therapy Program, Centenary Institute, Camperdown, New South Wales, Australia

    Jeff Holst, Sarah Watson & John E J Rasko

  2. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

    Jeff Holst & John E J Rasko

  3. Graduate School of Biomedical Engineering, The University of New South Wales, Sydney, New South Wales, Australia

    Megan S Lord

  4. School of Molecular Bioscience, University of Sydney, Sydney, New South Wales, Australia

    Steven S Eamegdool, Daniel V Bax, Lisa B Nivison-Smith & Anthony S Weiss

  5. School of Physics, University of Sydney, Sydney, New South Wales, Australia

    Alexey Kondyurin

  6. Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA

    Liang Ma & Andres F Oberhauser

  7. Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

    John E J Rasko

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Contributions

J.H. and J.E.J.R. designed the experiments and wrote the paper, J.H. and M.S.L. analyzed the data, J.H., S.W., A.F.O., L.M., S.S.E., M.S.L. and A.K. generated the data, A.S.W. and J.E.J.R. provided conceptual input and D.V.B., L.B.N.-S. and S.S.E. provided tropoelastin reagents.

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Correspondence to John E J Rasko.

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Competing interests

A.S.W. receives personal financial support from Elastagen Pty Ltd. A patent application has been filed for some of the technology disclosed in this publication.

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Holst, J., Watson, S., Lord, M. et al. Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells. Nat Biotechnol 28, 1123–1128 (2010). https://doi.org/10.1038/nbt.1687

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