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

0303 health sciences Myoblasts, Skeletal Muscle Proteins Mice, Inbred C57BL Mice 03 medical and health sciences Treatment Outcome Batch Cell Culture Techniques Animals Tissue Preservation Stem Cell Niche Cells, Cultured Stem Cell Transplantation
DOI: 10.1038/nbt.3576 Publication Date: 2016-05-30T17:10:20Z
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.
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