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Dystrophin expression in the mdx mouse restored by stem cell transplantation


The development of cell or gene therapies for diseases involving cells that are widely distributed throughout the body has been severely hampered by the inability to achieve the disseminated delivery of cells or genes to the affected tissues or organ1. Here we report the results of bone marrow transplantation studies in the mdx mouse, an animal model of Duchenne's muscular dystrophy2, which indicate that the intravenous injection of either normal haematopoietic stem cells or a novel population of muscle-derived stem cells into irradiated animals results in the reconstitution of the haematopoietic compartment of the transplanted recipients, the incorporation of donor-derived nuclei into muscle, and the partial restoration of dystrophin expression in the affected muscle. These results suggest that the transplantation of different stem cell populations, using the procedures of bone marrow transplantation, might provide an unanticipated avenue for treating muscular dystrophy as well as other diseases where the systemic delivery of therapeutic cells to sites throughout the body is critical. Our studies also suggest that the inherent developmental potential of stem cells isolated from diverse tissues or organs may be more similar than previously anticipated.

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We thank E. Snyder for the mouse Y-chromosome probe. This work was supported by the Muscular Dystrophy Association (L.M.K.), the Bernard and Alva Gimbel Foundation and Family (L.M.K.), the Howard Hughes Medical Institute (L.M.K., R.C.M.) and the NIH (R.C.M.). L.M.K. and R.C.M. are Investigators of the Howard Hughes Medical Institute.

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Correspondence to Louis M. Kunkel or Richard C. Mulligan.

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Figure 1: Dystrophin expression and detection of Y-chromosome-positive nuclei in the tibialis anterior muscle 12 weeks after whole bone marrow or haematopoietic stem cell transplantation into lethally irradiated female mdx recipients.
Figure 2: Isolation and characterization of muscle SP cells.
Figure 3: Detection of donor nuclei in the bone marrow and spleen of mdx recipients after injection of muscle SP cells.
Figure 4: Dystrophin-positive fibres were detected in skeletal muscle tissue sections of animals 3 and 1.


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