Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice
Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice
复制标题
DOI：
10.1007/s004290050237
复制
发表时间：
1999-05-01
期刊：
影响因子：
--
通讯作者：
Wachtler, F
中科院分区：
文献类型：
--
作者：
Bittner, RE;Schöfer, C;Wachtler, F
人们普遍认为，横纹肌的再生能力仅限于骨骼肌，而卫星细胞通常位于肌纤维的质膜和基底膜之间，处于静止状态。肌营养不良症的特点是骨骼肌纤维的反复降解和再生，以及心肌的频繁参与。由于在肌营养不良的长期病程中存在对成肌前体细胞的长期需求，我们假设这可能需要从未分化的、永久更新的细胞库中招募更多的成肌前体细胞，如骨髓细胞。为此，正常和营养不良(MDX)雌性小鼠接受了来自正常同源雄性供体小鼠的骨髓移植(BMT)。70天后，对骨髓移植小鼠的骨骼肌和心肌组织切片进行检测，以寻找供体来源的Y染色体。在正常的骨髓移植受者中，无论是在骨骼肌还是在心肌中，都没有检测到含有Y染色体的肌核。然而，在所有来自营养不良的MDX骨骼肌的样本中，Y染色体特异的信号都在肌肉纤维核中检测到，这些信号另外还被发现表达肌肉调节蛋白mygenin和Myf-5。此外，在BMT-MDX小鼠的心脏中发现了含有供体来源核的单个心肌细胞，这表明即使是心肌细胞也能够通过招募循环中的BM来源的祖细胞来再生。我们的发现表明，对能够进行肌源性分化的骨髓细胞的进一步表征和鉴定可能会对骨骼肌和心肌疾病的治疗策略产生显著影响。
It is commonly accepted, that regenerative capacity of striated muscle is confined to skeletal muscle by activation of satellite cells that normally reside quiescent between the plasmalemma and the basement membrane of muscle fibers. Muscular dystrophies are characterized by repetitive cycles of de- and regeneration of skeletal muscle fibers and by the frequent involvement of the cardiac muscle. Since during the longstanding course of muscular dystrophies there is a permanent demand of myogenic progenitors we hypothesized that this may necessitate a recruitment of additional myogenic precursors from an undifferentiated, permanently renewed cell pool, such as bone marrow (BM) cells. To this end normal and dystrophic (mdx) female mice received bone marrow transplantation (BMT) from normal congenic male donor mice. After 70 days, histological sections of skeletal and cardiac muscle from BMT mice were probed for the donor-derived Y chromosomes. In normal BMT recipients, no Y chromosome-containing myonuclei were detected, either in skeletal or in cardiac muscle. However, in all samples from dystrophic mdx skeletal muscles Y chromosome-specific signals were detected within muscle fiber nuclei, which additionally were found to express the myoregulatory proteins myogenin and myf-5. Moreover, in the hearts of BMT-mdx mice single cardiomyocytes with donor derived nuclei were identified, indicating, that even cardiac muscle cells are able to regenerate by recruitment of circulating BM-derived progenitors. Our findings suggest that further characterization and identification of the BM cells capable of undergoing myogenic differentiation may have an outstanding impact on therapeutic strategies for diseases of skeletal and cardiac muscle.