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

• Published in: The Journal of clinical investigation 2004-07, Vol.114 (2), p.182-195
• Main Authors: Torrente, Yvan, Belicchi, Marzia, Sampaolesi, Maurilio, Pisati, Federica, Meregalli, Mirella, D’Antona, Giuseppe, Tonlorenzi, Rossana, Porretti, Laura, Gavina, Manuela, Mamchaoui, Kamel, Pellegrino, Maria Antonietta, Furling, Denis, Mouly, Vincent, Butler-Browne, Gillian S., Bottinelli, Roberto, Cossu, Giulio, Bresolin, Nereo
• Format: Article
• Language: English
• ISSN: 0021-9738
• DOI: 10.1172/JCI200420325

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.