杜兴氏肌病患者中肌肉源性CD133 +干细胞的自体移植。

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.

作者信息

Torrente Y, Belicchi M, Marchesi C, D'Antona G, Cogiamanian F, Pisati F, Gavina M, Giordano R, Tonlorenzi R, Fagiolari G, Lamperti C, Porretti L, Lopa R, Sampaolesi M, Vicentini L, Grimoldi N, Tiberio F, Songa V, Baratta P, Prelle A, Forzenigo L, Guglieri M, Pansarasa O, Rinaldi C, Mouly V, Butler-Browne G S, Comi G P, Biondetti P, Moggio M, Gaini S M, Stocchetti N, Priori A, D'Angelo M G, Turconi A, Bottinelli R, Cossu G, Rebulla P, Bresolin N

机构信息

Fondazione IRCCS Ospedale Maggiore Policlinico of Milan, Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Italy.

出版信息

Cell Transplant. 2007;16(6):563-77. doi: 10.3727/000000007783465064.

DOI:10.3727/000000007783465064

PMID:17912948

Abstract

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.

摘要

杜氏肌营养不良症（DMD）是一种致命的X连锁隐性肌肉疾病，由编码抗肌萎缩蛋白的基因缺陷引起。肌肉中缺乏功能性抗肌萎缩蛋白会导致肌纤维膜脆弱，进而出现进行性肌肉无力和过早死亡。目前尚无治愈DMD的方法，当前的治疗方案主要集中在呼吸辅助、舒适护理以及延缓行走能力丧失。最近的研究支持干细胞有助于肌肉修复以及补充卫星细胞池这一观点。在此，我们在一项为期7个月的双盲I期临床试验中，对8名杜氏肌营养不良症男孩进行了肌肉来源的CD133+细胞自体移植的安全性测试。通过测量肌肉力量以及利用MRI和组织学分析评估肌肉结构来测试干细胞安全性。定时心脏和肺功能测试为次要结局指标。在所有接受治疗的DMD患者中均未观察到局部或全身副作用。接受治疗的患者每根肌纤维的毛细血管比例增加，并且肌球蛋白阳性肌纤维从慢肌纤维转变为快肌纤维。