Efficient conversion of ES cells into myogenic lineage using the gene-inducible system.
We established genetically engineered ES (ZHTc6-MyoD) cells that harbor a tetracycline-regulated expression vector encoding myogenic transcriptional factor MyoD, for the therapy of muscle diseases, especially Duchenne muscular dystrophy (DMD). Almost all the ZHTc6-MyoD cells were induced into muscle lineage after removal of tetracycline. The undifferentiated ZHTc6-MyoD cells are Sca-1+ and c-kit+, but CD34-, all well-known markers for mouse hematopoietic stem cells. In addition, they are able to maintain themselves in the undifferentiated state, even after one month of culture. Therefore, it is possible to obtain a large quantity of ZHTc6-MyoD cells in the undifferentiated state that maintain the potential to differentiate only into muscle lineage. Additionally, at two weeks post-injection of these cells into muscle of mdx, a model mouse of DMD, clusters of dystrophin-positive myofibers were observed at the injection site. Therefore, ES cells have considerable therapeutic potential for treating muscle diseases.
Ozasa
Shiro
S
Department of Child Development, Kumamoto University Graduate School, 1-1-1 Honjo, Kumamoto City, Kumamoto 862-8556, Japan.
Kimura
Shigemi
S
Ito
Kaori
K
Ueno
Hiroe
H
Ikezawa
Makoto
M
Matsukura
Makoto
M
Yoshioka
Kowashi
K
Araki
Kimi
K
Yamamura
Ken-ich
KI
Abe
Kuniya
K
Niwa
Hitoshi
H
Miike
Teruhisa
T
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D051379:Mice; D032342:Muscle Cells / Q000166:cytology* / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics*; D023822:Tissue Engineering / Q000379:methods
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein