Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration.
Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell-mediated therapies.
Qu-Petersen
Zhuqing
Z
Growth and Development Laboratory, Children's Hospital of Pittsburgh, Department of Orthopaedic Surgery, University of Pittsburgh, PA 15260, USA.
Deasy
Bridget
B
Jankowski
Ron
R
Ikezawa
Makato
M
Cummins
James
J
Pruchnic
Ryan
R
Mytinger
John
J
Cao
Baohong
B
Gates
Charley
C
Wernig
Anton
A
Huard
Johnny
J
D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D016189:Dystrophin / Q000502:physiology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D066298:In Vitro Techniques; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology; D020932:Nerve Growth Factor / Q000494:pharmacology; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016189:Dystrophin; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020932:Nerve Growth Factor