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Science 329 (5995): 1078-1081

Copyright © 2010 by the American Association for the Advancement of Science

Substrate Elasticity Regulates Skeletal Muscle Stem Cell Self-Renewal in Culture

P. M. Gilbert,1,* K. L. Havenstrite,1,2,* K. E. G. Magnusson,1,3 A. Sacco,1,{dagger} N. A. Leonardi,1,4 P. Kraft,1 N. K. Nguyen,1 S. Thrun,5 M. P. Lutolf,4 H. M. Blau1,{ddagger}

Abstract: Stem cells that naturally reside in adult tissues, such as muscle stem cells (MuSCs), exhibit robust regenerative capacity in vivo that is rapidly lost in culture. Using a bioengineered substrate to recapitulate key biophysical and biochemical niche features in conjunction with a highly automated single-cell tracking algorithm, we show that substrate elasticity is a potent regulator of MuSC fate in culture. Unlike MuSCs on rigid plastic dishes (~106 kilopascals), MuSCs cultured on soft hydrogel substrates that mimic the elasticity of muscle (12 kilopascals) self-renew in vitro and contribute extensively to muscle regeneration when subsequently transplanted into mice and assayed histologically and quantitatively by noninvasive bioluminescence imaging. Our studies provide novel evidence that by recapitulating physiological tissue rigidity, propagation of adult muscle stem cells is possible, enabling future cell-based therapies for muscle-wasting diseases.

1 Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
3 School of Electrical Engineering, Signal Processing Lab, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden.
4 Institute of Bioengineering and Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
5 Stanford Artificial Intelligence Lab, Department of Computer Science, Stanford, CA 94305, USA.

* These authors contributed equally to this work.

{dagger} Present address: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.

{ddagger} To whom correspondence should be addressed. E-mail: hblau{at}stanford.edu


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