MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle
MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle
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DOI：
10.1073/pnas.0603386103
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发表时间：
2006-11-07
影响因子：
11.1
通讯作者：
Cossu, Giulio
中科院分区：
文献类型：
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作者：
Morosetti, Roberta;Mirabella, Massimiliano;Cossu, Giulio
炎症性肌病 (IM) 是一种获得性骨骼肌疾病，包括皮肌炎 (DM)、多发性肌炎 (PM) 和包涵体肌炎 (IBM)。免疫抑制疗法通常对 DM 和 PM 有益，但对 IBM 效果不佳。我们报告了从 IM 诊断性肌肉活检中分离和鉴定中成血管细胞（血管相关干细胞）的情况。正常和IM中成血管细胞的分离细胞数量、增殖率和寿命、标记物表达以及分化为平滑肌的能力没有差异。与正常情况不同的是，从 IBM 分离的 DM 和 PM 中成血管细胞无法分化为骨骼肌管。这些数据与 IBM 肌肉结缔组织中碱性磷酸酶 (ALP) 阳性细胞的缺乏相关，相反，PM 和 DM 中的结缔组织显着增加。肌源性抑制性碱性螺旋-环-螺旋因子 B3 在 IBM 中成血管细胞中高度表达。事实上，沉默该基因或过度表达 MyoD 可以挽救 IBM 中成血管细胞的肌源性缺陷，为这种严重疾病开辟新的基于细胞的治疗策略。
Inflammatory myopathies (IM) are acquired diseases of skeletal muscle comprising dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). Immunosuppressive therapies, usually beneficial for DM and PM, are poorly effective in IBM. We report the isolation and characterization of mesoangioblasts, vessel-associated stem cells, from diagnostic muscle biopsies of IM. The number of cells isolated, proliferation rate and lifespan, markers expression, and ability to differentiate into smooth muscle do not differ among normal and IM mesoangioblasts. At variance with normal, DM and PM mesoangioblasts, cells isolated from IBM, fail to differentiate into skeletal myotubes. These data correlate with lack in connective tissue of IBM muscle of alkaline phosphatase (ALP)-positive cells, conversely dramatically increased in PM and DM. A myogenic inhibitory basic helix-loop-helix factor B3 is highly expressed in IBM mesoangioblasts. Indeed, silencing this gene or overexpressing MyoD rescues the myogenic defect of IBM mesoangioblasts, opening novel cell-based therapeutic strategies for this crippling disorder.