Skeletal myoblast transplantation for repair of myocardial necrosis
Skeletal myoblast transplantation for repair of myocardial necrosis
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DOI：
10.1172/jci119070
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发表时间：
1996-12-01
影响因子：
15.9
通讯作者：
Hauschka, SD
中科院分区：
文献类型：
--
作者：
Murry, CE;Wiseman, RW;Hauschka, SD
心肌梗死通过疤痕愈合，因为心肌不能再生。为确定骨骼肌母细胞能否形成新的收缩组织，用冻融法损伤成年近交系大鼠心脏，然后立即移植3~4.5×10(6)的新生大鼠骨骼肌细胞。1d时移植物细胞开始增殖，肌球蛋白重链(MHC)不表达。3d时，可见多核肌管同时表达胚胎和快纤维MHC。在2wk时，电子显微镜显示可能存在卫星干细胞。到7周时，移植物开始表达β-MHC，这是慢纤维表型的标志；胚胎、快速和β-MHC的共同表达持续了3个月。损伤后1wk移植成肌细胞可产生类似的结果，只是移植物表达β-MHC的时间更早(到2wk)。移植物从未表达过心脏特异的MHC-α。含有2周龄成肌细胞移植物的伤口在体外受到刺激时会收缩，高频刺激会导致破伤风。此外，移植物可以执行类似心脏的占空比，交替破伤风和松弛，至少6分钟。因此，骨骼肌成肌细胞在移植到受伤的心脏上时可以建立新的肌肉组织，而当受到电刺激时，这块肌肉可以收缩。因为移植物会转化为耐疲劳的慢抽动纤维，这种新的肌肉可能适合心脏负荷。
Myocardial infarcts heal by scarring because myocardium cannot regenerate. To determine if skeletal myoblasts could establish new contractile tissue, hearts of adult inbred rats were injured by freeze-thaw, and 3-4.5 x 10(6) neonatal skeletal muscle cells were transplanted immediately thereafter. At 1 d the graft cells were proliferating and did not express myosin heavy chain (MHC). By 3 d, multinucleated myotubes were present which expressed both embryonic and fast fiber MHCs. At 2 wk, electron microscopy demonstrated possible satellite stem cells. By 7 wk the grafts began expressing beta-MHC, a hallmark of the slow fiber phenotype; coexpression of embryonic, fast, and beta-MHC continued through 3 mo. Transplanting myoblasts 1 wk after injury yielded comparable results, except that grafts expressed beta-MHC sooner (by 2 wk). Grafts never expressed cardiac-specific MHC-alpha. Wounds containing 2-wk-old myoblast grafts contracted when stimulated ex vivo, and high frequency stimulation induced tetanus. Furthermore, the grafts could perform a cardiac-like duty cycle, alternating tetanus and relaxation, for at least 6 min. Thus, skeletal myoblasts can establish new muscle tissue when grafted into injured hearts, and this muscle can contract when stimulated electrically. Because the grafts convert to fatigue-resistant, slow twitch fibers, this new muscle may be suited to a cardiac work load.