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Nat Biotechnol. 2016 Jul;34(7):752-9. doi: 10.1038/nbt.3576. Epub 2016 May 30.

An artificial niche preserves the quiescence of muscle stem cells and enhances their therapeutic efficacy.

Author information

1
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
2
Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
3
Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
4
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
5
Department of Bioengineering, Stanford University, Stanford, California, USA.
6
Department of Materials Science and Engineering, Stanford University, Stanford, California, USA.
7
Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California, USA.

Abstract

A promising therapeutic strategy for diverse genetic disorders involves transplantation of autologous stem cells that have been genetically corrected ex vivo. A major challenge in such approaches is a loss of stem cell potency during culture. Here we describe an artificial niche for maintaining muscle stem cells (MuSCs) in vitro in a potent, quiescent state. Using a machine learning method, we identified a molecular signature of quiescence and used it to screen for factors that could maintain mouse MuSC quiescence, thus defining a quiescence medium (QM). We also engineered muscle fibers that mimic the native myofiber of the MuSC niche. Mouse MuSCs maintained in QM on engineered fibers showed enhanced potential for engraftment, tissue regeneration and self-renewal after transplantation in mice. An artificial niche adapted to human cells similarly extended the quiescence of human MuSCs in vitro and enhanced their potency in vivo. Our approach for maintaining quiescence may be applicable to stem cells isolated from other tissues.

PMID:
27240197
PMCID:
PMC4942359
DOI:
10.1038/nbt.3576
[Indexed for MEDLINE]
Free PMC Article

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