title: An artificial niche preserves the quiescence of muscle stem cells and enhances their therapeutic efficacy.
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.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Quarta
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jamie O
authors.initials: JO
authors.lastname: Brett
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: DiMarco
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Antoine
authors.initials: A
authors.lastname: De Morree
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Stephane C
authors.initials: SC
authors.lastname: Boutet
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Chacon
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Michael C
authors.identifier: 0000-0002-3039-9839
authors.initials: MC
authors.lastname: Gibbons
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Garcia
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, California, USA.
authors.forename: James
authors.initials: J
authors.lastname: Su
authors.affiliation: Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, California, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Heilshorn
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.|Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, California, USA.|Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
mesh_terms: D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D055153:Stem Cell Niche / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D014021:Tissue Preservation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D009124:Muscle Proteins