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

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.