Berry Suzanne E, Liu Jianming, Chaney Eric J, Kaufman Stephen J
University of Illinois, Department of Cell and Developmental Biology, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
Regen Med. 2007 May;2(3):275-88. doi: 10.2217/17460751.2.3.275.
Duchenne muscular dystrophy is a progressive, lethal muscle-wasting disease for which there is no treatment.
MATERIALS & METHODS: We have isolated wild-type mesoangioblasts from aorta and tested their effectiveness in alleviating severe muscle disease in the dystrophin/utrophin knockout (mdx/utrn-/-) mouse model for Duchenne muscular dystrophy.
Mesoangioblast clones express Sca-1 and Flk-1 and differentiate into smooth and skeletal muscle, glial cells and adipocytes in vitro. Mesoangioblasts proliferate in vivo, incorporate into muscle fibers, form new fibers, and promote synthesis of dystrophin and utrophin. Muscle fibers that have incorporated mesoangioblasts, as well as surrounding fibers, are protected from damage, with approximately 50-fold less damage than fibers in muscle injected with saline. Some mesoangioblasts localize beneath the basal lamina and express c-met, whereas others differentiate into smooth muscle cells at the periphery of vessels and express alpha-smooth muscle actin. In mdx/utrn-/- muscle, some mesoangioblasts also form Schwann cells.
DISCUSSION & CONCLUSION: Mesoangioblasts differentiate into multiple cell types damaged during the progression of severe muscle disease and protect fibers from damage. As such, they are good candidates for therapy of Duchenne muscular dystrophy and perhaps other neuromuscular diseases.
杜兴氏肌营养不良症是一种进行性致死性肌肉萎缩疾病，目前尚无治疗方法。
我们从主动脉中分离出野生型间充质血管干细胞，并在杜兴氏肌营养不良症的肌营养不良蛋白/抗肌萎缩蛋白基因敲除（mdx/utrn-/-）小鼠模型中测试了它们缓解严重肌肉疾病的效果。
间充质血管干细胞克隆表达Sca-1和Flk-1，并在体外分化为平滑肌、骨骼肌、神经胶质细胞和脂肪细胞。间充质血管干细胞在体内增殖，整合到肌纤维中，形成新的纤维，并促进肌营养不良蛋白和抗肌萎缩蛋白的合成。整合了间充质血管干细胞的肌纤维以及周围的纤维受到保护，免受损伤，其损伤程度比注射生理盐水的肌肉中的纤维少约50倍。一些间充质血管干细胞定位于基膜下方并表达c-met，而另一些则在血管周围分化为平滑肌细胞并表达α-平滑肌肌动蛋白。在mdx/utrn-/-肌肉中，一些间充质血管干细胞还形成施万细胞。
间充质血管干细胞分化为严重肌肉疾病进展过程中受损的多种细胞类型，并保护纤维免受损伤。因此，它们是治疗杜兴氏肌营养不良症以及其他神经肌肉疾病的良好候选细胞。
