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

Jeff Holst, Sarah Watson, Megan S. Lord, Steven S. Eamegdool, Daniel V. Bax, Lisa B. Nivison-Smith, Alexey Kondyurin, Liang Ma, Andres F. Oberhauser, Anthony S. Weiss, John E.J. Rasko

Research output: Contribution to journalArticle

186 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1123-1128
Number of pages6
JournalNature Biotechnology
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2010

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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    Holst, J., Watson, S., Lord, M. S., Eamegdool, S. S., Bax, D. V., Nivison-Smith, L. B., Kondyurin, A., Ma, L., Oberhauser, A. F., Weiss, A. S., & Rasko, J. E. J. (2010). Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells. Nature Biotechnology, 28(10), 1123-1128. https://doi.org/10.1038/nbt.1687