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 / Y. Torrente, M. Belicchi, M. Sampaolesi, F. Pisati, M. Meregalli, G. D'Antona, R. Tonlorenzi, L. Porretti, M. Gavina, K. Mamchaoui, M.A. Pellegrino, D. Furling, V. Mouly, G.S. Butler Browne, R. Bottinelli, G. Cossu, N. Bresolin. - 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
Y. TorrentePrimo
;M. BelicchiSecondo
;M. Meregalli;G. CossuPenultimo
;N. BresolinUltimo
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.File | Dimensione | Formato | |
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