Project/Area Number |
19790749
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Pediatrics
|
Research Institution | National Research Institute for Child Health and Development |
Principal Investigator |
SAI Syoko National Research Institute for Child Health and Development, 生殖・細胞医療研究部, 流動研究員 (80392497)
|
Project Period (FY) |
2007 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
Keywords | 筋ジストロフィー / 周産期幹細胞 / 幹細胞 / 骨格筋 / 細胞移植 / 筋ジストロフー |
Research Abstract |
Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder in children, is an X-linked recessive muscle disease characterized by the absence of dystrophin at the sarcolemma of muscle fibers. We examined a putative mesenchymal stromal cells obtained from endometrial or placenta tissue samples to determine whether these cells repair muscular degeneration in a murine mdx model of DMD. Implanted cells conferred human dystrophin in degenerated muscle of immunodeficient mdx mice. We then examined endometrial-derived cells, menstrual blood-derived cells, and placenta-derived cell to determine whether primarily cultured nontransformed cells also repair dystrophied muscle. In vivo transfer of these cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of dystrophin. Labeling of implanted cells with enhanced green fluorescent protein and differential staining of human and murine nuclei suggest that human dystrophin expression is due to cell fusion between host myocytes and implanted cells. In vitro analysis revealed that cells can efficiently transdifferentiate into myoblasts/myocytes, fuse to C2C12 murine myoblasts by in vitro coculturing, and start to express dystrophin after fusion. These results demonstrate that the endometrial-derived cells, menstrual blood-derived cells, and placenta-derived cell can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo.
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