期刊
CELL TRANSPLANTATION
卷 21, 期 7, 页码 1407-1417出版社
SAGE PUBLICATIONS INC
DOI: 10.3727/096368911X
关键词
Human multipotent mesenchymal stromal cells; Xenotransplantation; Muscular dystrophy; Therapy
资金
- FAPESP-CEPID (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-Centro de Pesquisa, Inovacao e Difusao)
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- INCT (Instituto Nacional de Ciencia e Tecnologia)
- ABDIM (Associacao Brasileira de Distrofia Muscular)
Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, is the most common and severe form of muscular dystrophies, affecting I in 3,500 male births. Mutations in the DMD gene lead to the absence of muscle dystrophin and a progressive degeneration of skeletal muscle. The possibility to treat DMD through cell therapy has been widely investigated. We have previously shown that human adipose-derived stromal cells (hASCs) injected systemically in SJL mice are able to reach and engraft in the host muscle, express human muscle proteins, and ameliorate the functional performance of injected animals without any immunosuppression. However, before starting clinical trials in humans many questions still need to be addressed in preclinical studies, in particular in larger animal models, when available. The best animal model to address these questions is the golden retriever muscular dystrophy (GRMD) dog that reproduces the full spectrum of human DMD. Affected animals carry a mutation that predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. These dogs present clinical signs within the first weeks and most of them do not survive beyond age two. Here we show the results of local and intravenous injections of hASCs into GRMD dogs, without immunosuppression. We observed that hASCs injected systemically into the dog cephalic vein are able to reach, engraft, and express human dystrophin in the host GRMD dystrophic muscle up to 6 months after transplantation. Most importantly, we demonstrated that injecting a huge quantity of human mesenchymal cells in a large-animal model, without immunosuppression, is a safe procedure, which may have important applications for future therapy in patients with different forms of muscular dystrophies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据