Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation

Gussoni, Emanuela; Bennett, Richard Rodney; Muskiewicz, Kristina R.; Meyerrose, Todd E.; Nolta, Jan A.; Gilgoff, Irene S.; Stein, James H.; Chan, Yiu-mo; Lidov, Hart G.W.; Bönnemann, Carsten G.; Moers, Arpad von; Morris, Glenn E.; Dunnen, Johan T. den; Chamberlain, Jeffrey S.; Kunkel, Louis M.; Weinberg, Kenneth I.

doi:10.1172/jci200216098

Cited by 89 publications

(100 citation statements)

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“…Evidence that bone marrow (BM)-derived cells can give rise to skeletal muscle fibers [5][6][7][8] and restore dystrophin in vivo 9 has suggested a possible benefit of BM-derived cell transplantation in the treatment of DMD in the future. 10 However, efficiency of fusion of circulating BM-derived cells with pre-existing muscle fibers appears somewhat discrepant in the literature. On the one hand, experiments using transplantation of green fluorescent protein (GFP)-expressing BM cells in normal irradiated mice have convincingly demonstrated the presence of GFP ϩ muscle fibers assessing prior fusion with BM-derived cells.…”

mentioning

confidence: 99%

In Vivo Fusion of Circulating Fluorescent Cells with Dystrophin-Deficient Myofibers Results in Extensive Sarcoplasmic Fluorescence Expression but Limited Dystrophin Sarcolemmal Expression

Chrétien

Dreyfus

Christov

et al. 2005

The American Journal of Pathology

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To investigate the therapeutic potential of bone marrow transplantation in Duchenne muscular dystrophy, green fluorescent protein-positive (GFP ؉ ) bone marrow cells were transplanted into irradiated wildtype and dystrophin-deficient mdx mice. Tibialis anterior muscles showed fivefold to sixfold more GFP ؉ mononucleated cells and threefold to fourfold more GFP ؉ myofibers in mdx than in wild-type mice. In contrast, dystrophin expression in mdx mice remained within the level of nontransplanted mdx mice, and co-expression with GFP was rare. Longitudinal sections of 5000 myofibers showed 160 GFP ؉ fibers, including 9 that co-expressed dystrophin. GFP was always visualized as full-length sarcoplasmic fluorescence that exceeded the span of sample length (up to 1500 m), whereas dystrophin expression was restricted to 11 to 28% of this length. Dystrophin expression span was much shorter in GFP ؉ fibers (116 ؎ 46 m) than in revertant fibers (654 ؎ 409 m). These data suggest that soluble GFP diffuses far from the fusion site with a pre-existing dystrophin ؊ myofiber whereas dystrophin remains mainly expressed close to the site of fusion. Because restoration of dystrophin in whole muscle fiber length is required to expect functional improvement and clinical benefits for Duchenne muscular dystrophy, future applications of cell therapies to neuromuscular disorders could be more appropriately envisaged for re-

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mentioning

confidence: 99%

In Vivo Fusion of Circulating Fluorescent Cells with Dystrophin-Deficient Myofibers Results in Extensive Sarcoplasmic Fluorescence Expression but Limited Dystrophin Sarcolemmal Expression

Chrétien

Dreyfus

Christov

et al. 2005

The American Journal of Pathology

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“…Unlike MSC, MAPC can be cultured indefinitely in a relatively nutrient-poor medium. MAPC exhibit many of the features and capabilities of embryonic stem cells [14][15][16][17][18][19][20][21][22][23][24].…”

Section: Multipotent Adult Progenitor Cellsmentioning

confidence: 99%

“…In patients in whom autologous bone marrow cells were injected directly into the damaged myocardium, some improvement in cardiac function was documented based on medication use, quality of life and MRI studies [17]. In a separate study, after autologous AC 133+ bone marrow cells were injected into infarction borders following coronary artery bypass grafting (CABG), improved perfusion and cardiac function may have occurred [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: Demonstration Of Bone Marrow Plasticitymentioning

confidence: 99%

“…Furthermore, BM transplantation restores low levels of dystrophin expression to the muscles of index mice, which lack the gene for dystrophin. A case report [19] describes a boy with a relatively mild Duchenne Muscular Dystrophy (DMD) diagnosed when he was 12 years old. He had undergone allogeneic BMT for X-linked severe combined immunodeficiency syndrome (SCID) when he was one year old.…”

Section: Demonstration Of Bone Marrow Plasticitymentioning

confidence: 99%

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Adult Stem Cell Plasticity: Dream or Reality?

Chatterjee

Sarkar

Dhot³

et al. 2010

Medical Journal Armed Forces India

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“…70,71 This finding has not be validated. 72 In 2002, Gussoni, et al 73 reported the case of a 12-year-old boy with DMD who had a bone marrow transplant for severe combined immunodeficiency at the age of one year. The muscle biopsy from this patient showed the presence of donor nuclei in less than one percent of the muscle fibers, demonstrating the ability of exogenous bone marrow cells to fuse into skeletal muscle and last more than a decade.…”

Section: Cell Therapymentioning

confidence: 99%

Therapeutics in Duchenne muscular dystrophy

Strober

2006

NeuroRX

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Summary: Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation

Cited by 89 publications

References 50 publications

In Vivo Fusion of Circulating Fluorescent Cells with Dystrophin-Deficient Myofibers Results in Extensive Sarcoplasmic Fluorescence Expression but Limited Dystrophin Sarcolemmal Expression

In Vivo Fusion of Circulating Fluorescent Cells with Dystrophin-Deficient Myofibers Results in Extensive Sarcoplasmic Fluorescence Expression but Limited Dystrophin Sarcolemmal Expression

Adult Stem Cell Plasticity: Dream or Reality?

Therapeutics in Duchenne muscular dystrophy

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