Muscle reconstitution by muscle satellite cell descendants with stem cell-like properties.
Recent studies have demonstrated that a distinct subpopulation with stem cell-like characteristics in myoblast culture is responsible for new muscle fiber formation after intramuscular transplantation. The identification and isolation of stem-like cells would have significant implications for successful myogenic cell transfer therapy in human muscle disorders. Using a clonal culture system for mouse muscle satellite cells, we have identified two cell types, designated 'round cells' and 'thick cells', in clones derived from single muscle satellite cells that have been taken from either slow or fast muscle. Clonal analysis of satellite cells revealed that the round cells are immediate descendants of quiescent satellite cells in adult muscle. In single-myofiber culture, round cells first formed colonies and then generated progeny, thick cells, that underwent both myogenic and osteogenic terminal differentiation under the appropriate culture conditions. Thick cells, but not round cells, responded to terminal differentiation-inducing signals. Round cells express Pax7, a specific marker of satellite cells, at high levels. Myogenic cell transfer experiments showed that round cells reconstitute myofibers more efficiently than thick cells. Furthermore, round cells restored dystrophin in myofibers of mdx nude mice, even when as few as 5000 cells were transferred into the gastrocnemius muscle. These results suggest that round cells are satellite-cell descendants with stem cell-like characteristics and represent a useful source of donor cells to improve muscle regeneration.
Tissue Stem Cell Research Team, Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. nao@libra.ls.m-kagaku.co.jp
Naohiro
N
Hashimoto
Takeshi
T
Murase
Syunzo
S
Kondo
Asuko
A
Okuda
Masayo
M
Inagawa-Ogashiwa
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D016189:Dystrophin / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D051379:Mice; D008855:Microscopy, Electron, Scanning; D024510:Muscle Development / Q000187:drug effects; D009132:Muscles / Q000166:cytology* / Q000378:metabolism*; D051763:PAX7 Transcription Factor; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016189:Dystrophin; D018398:Homeodomain Proteins; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2