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Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy.
Stem Cell Reports. 2018 03 13; 10(3):942-955.SC

Abstract

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes. Surprisingly, CDCs and their exosomes also transiently restored partial expression of full-length dystrophin in mdx mice. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.

Authors+Show Affiliations

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.UCLA Technology Center for Genomics & Bioinformatics, Los Angeles, CA 90095, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA.Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite AHSP 3100, Los Angeles, CA 90048, USA. Electronic address: eduardo.marban@cshs.org.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29478899

Citation

Aminzadeh, Mark A., et al. "Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy." Stem Cell Reports, vol. 10, no. 3, 2018, pp. 942-955.
Aminzadeh MA, Rogers RG, Fournier M, et al. Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy. Stem Cell Reports. 2018;10(3):942-955.
Aminzadeh, M. A., Rogers, R. G., Fournier, M., Tobin, R. E., Guan, X., Childers, M. K., Andres, A. M., Taylor, D. J., Ibrahim, A., Ding, X., Torrente, A., Goldhaber, J. M., Lewis, M., Gottlieb, R. A., Victor, R. A., & Marbán, E. (2018). Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy. Stem Cell Reports, 10(3), 942-955. https://doi.org/10.1016/j.stemcr.2018.01.023
Aminzadeh MA, et al. Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy. Stem Cell Reports. 2018 03 13;10(3):942-955. PubMed PMID: 29478899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy. AU - Aminzadeh,Mark A, AU - Rogers,Russell G, AU - Fournier,Mario, AU - Tobin,Rachel E, AU - Guan,Xuan, AU - Childers,Martin K, AU - Andres,Allen M, AU - Taylor,David J, AU - Ibrahim,Ahmed, AU - Ding,Xiangming, AU - Torrente,Angelo, AU - Goldhaber,Joshua M, AU - Lewis,Michael, AU - Gottlieb,Roberta A, AU - Victor,Ronald A, AU - Marbán,Eduardo, Y1 - 2018/03/01/ PY - 2017/12/14/received PY - 2018/01/20/revised PY - 2018/01/22/accepted PY - 2018/2/27/pubmed PY - 2019/2/13/medline PY - 2018/2/27/entrez KW - cardiomyopathy KW - cardiosphere-derived cells KW - dystrophin KW - exosomes KW - microRNA KW - muscular dystrophy SP - 942 EP - 955 JF - Stem cell reports JO - Stem Cell Reports VL - 10 IS - 3 N2 - Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes. Surprisingly, CDCs and their exosomes also transiently restored partial expression of full-length dystrophin in mdx mice. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates. SN - 2213-6711 UR - https://www.unboundmedicine.com/medline/citation/29478899/Exosome_Mediated_Benefits_of_Cell_Therapy_in_Mouse_and_Human_Models_of_Duchenne_Muscular_Dystrophy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-6711(18)30049-3 DB - PRIME DP - Unbound Medicine ER -