Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles.
Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2-4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50-70 fiber-associated, or 1,000-5,000 FACS-enriched CD56(+)/CD29(+) human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Xiaoti
X
Xu
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Karlijn J
KJ
Wilschut
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Gayle
G
Kouklis
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Hua
H
Tian
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Robert
R
Hesse
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Catharine
C
Garland
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Hani
H
Sbitany
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Scott
S
Hansen
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Rahul
R
Seth
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
P Daniel
PD
Knott
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
William Y
WY
Hoffman
Division of Plastic and Reconstructive Surgery, Departments of Surgery and Orofacial Sciences, Program in Craniofacial Biology, Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jason.pomerantz@ucsf.edu.
Jason H
JH
Pomerantz
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration; D044968:Regenerative Medicine; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
D000943:Antigens, Differentiation