Evidence for a myogenic stem cell that is exhausted in dystrophic muscle.
Evidence for a myogenic stem cell that is exhausted in dystrophic muscle.
复制标题
DOI：
--
复制
发表时间：
2000-06
影响因子：
4
通讯作者：
L. Heslop;Jennifer E. Morgan;Terence A. Partridge
中科院分区：
文献类型：
--
作者：
L. Heslop;Jennifer E. Morgan;Terence A. Partridge
发现注射肌肉毒素notexin可以诱导受到18戈伊辐射的肌肉再生。这一发现是出乎意料的，因为已知这种量级的辐射剂量会阻断营养不良（mdx）小鼠肌肉的再生。为了进一步研究这种现象，我们对mdx和正常（C57 B1/10）肌肉进行照射和notexin治疗，并以两种方式分析它们。首先通过计数受损肌肉冷冻切片中表达发育肌球蛋白的新再生肌纤维的数量。第二，通过从处理的肌肉中分离单个肌纤维并计数在2天和5天期间从这些肌纤维中产生的肌肉前体细胞的数量。照射后，正常或营养不良的肌肉都不能再生到任何显著的程度。此外，从这样的肌肉培养的单个肌纤维产生非常少的肌肉前体细胞，并且这些细胞很少或没有增殖。然而，当照射正常和mdx肌肉随后用notexin处理时，观察到再生。此外，一些单肌纤维产生快速增殖的肌肉前体细胞培养时。这种情况发生得更频繁，肌源性细胞增殖更广泛，与营养不良的肌肉相比，正常肌肉中培养出的纤维。即使在25戈伊后，notexin诱导一些再生，但没有增殖的肌源性细胞仍然与肌纤维相关。因此，骨骼肌含有许多功能不同的肌源性细胞群。大多数人对辐射敏感。然而，一些存活18戈伊的增殖肌源性细胞，可以诱发的极端条件下的肌肉损伤;这一人口是显着减少的mdx小鼠的肌肉。一个小的第三人口生存25戈伊，并形成肌肉，但不增殖肌原细胞。
Injection of the myotoxin notexin, was found to induce regeneration in muscles that had been subjected to 18 Gy of radiation. This finding was unexpected as irradiation doses of this magnitude are known to block regeneration in dystrophic (mdx) mouse muscle. To investigate this phenomenon further we subjected mdx and normal (C57Bl/10) muscle to irradiation and notexin treatment and analysed them in two ways. First by counting the number of newly regenerated myofibres expressing developmental myosin in cryosections of damaged muscles. Second, by isolating single myofibres from treated muscles and counting the number of muscle precursor cells issuing from these over 2 day and 5 day periods. After irradiation neither normal nor dystrophic muscles regenerate to any significant extent. Moreover, single myofibres cultured from such muscles produce very few muscle precursor cells and these undergo little or no proliferation. However, when irradiated normal and mdx muscles were subsequently treated with notexin, regeneration was observed. In addition, some of the single myofibres produced rapidly proliferative muscle precursor cells when cultured. This occurred more frequently, and the myogenic cells proliferated more extensively, with fibres cultured from normal compared with dystrophic muscles. Even after 25 Gy, notexin induced some regeneration but no proliferative myogenic cells remained associated with the muscle fibres. Thus, skeletal muscles contain a number of functionally distinct populations of myogenic cells. Most are radiation sensitive. However, some survive 18 Gy as proliferative myogenic cells that can be evoked by extreme conditions of muscle damage; this population is markedly diminished in muscles of the mdx mouse. A small third population survives 25 Gy and forms muscle but not proliferative myogenic cells.