Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. Here we report that a subpopulation of circulating cells expressing AC133, a well-characterized marker of hematopoietic stem cells, also expresses early myogenic markers. Freshly isolated, circulating AC133+ cells were induced to undergo myogenesis when cocultured with myogenic cells or exposed to Wnt-producing cells in vitro and when delivered in vivo through the arterial circulation or directly into the muscles of transgenic scid/mdx mice (which allow survival of human cells). Injected cells also localized under the basal lamina of host muscle fibers and expressed satellite cell markers such as M-cadherin and MYF5. Furthermore, functional tests of injected muscles revealed a substantial recovery of force after treatment. As these cells can be isolated from the blood, manipulated in vitro, and delivered through the circulation, they represent a possible tool for future cell therapy applications in DMD disease or other muscular dystrophies.

Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle / Torrente, Y; Belicchi, M; Sampaolesi, Maurilio; Pisati, F; Meregalli, M; D'Antona, Giuseppe; Tonlorenzi, R; Porretti, L; Gavina, M; Mamchaoui, K; Pellegrino, Maria Antonietta; Furling, D; Mouly, V; Butler Browne, Gs; Bottinelli, Roberto; Cossu, G; Bresolin, N.. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - 114:2(2004), pp. 182-195. [10.1172/JCI20325]

Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle

SAMPAOLESI, MAURILIO;
2004

Abstract

Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease. Here we report that a subpopulation of circulating cells expressing AC133, a well-characterized marker of hematopoietic stem cells, also expresses early myogenic markers. Freshly isolated, circulating AC133+ cells were induced to undergo myogenesis when cocultured with myogenic cells or exposed to Wnt-producing cells in vitro and when delivered in vivo through the arterial circulation or directly into the muscles of transgenic scid/mdx mice (which allow survival of human cells). Injected cells also localized under the basal lamina of host muscle fibers and expressed satellite cell markers such as M-cadherin and MYF5. Furthermore, functional tests of injected muscles revealed a substantial recovery of force after treatment. As these cells can be isolated from the blood, manipulated in vitro, and delivered through the circulation, they represent a possible tool for future cell therapy applications in DMD disease or other muscular dystrophies.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1581807
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