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Engraftment of human induced pluripotent stem cell-derived myogenic progenitors restores dystrophin in mice with duchenne muscular dystrophy.
Biol Res. 2020 May 19; 53(1):22.BR

Abstract

BACKGROUND

Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder with no effective treatment that is caused by the loss of dystrophin. Human induced pluripotent stem cells (hiPSCs) offer a promising unlimited resource for cell-based therapies of muscular dystrophy. However, their clinical applications are hindered by inefficient myogenic differentiation, and moreover, the engraftment of non-transgene hiPSC-derived myogenic progenitors has not been examined in the mdx mouse model of DMD.

METHODS

We investigated the muscle regenerative potential of myogenic progenitors derived from hiPSCs in mdx mice. The hiPSCs were transfected with enhanced green fluorescent protein (EGFP) vector and defined as EGFP hiPSCs. Myogenic differentiation was performed on EGFP hiPSCs with supplementary of basic fibroblast growth factor, forskolin, 6-bromoindirubin-3'-oxime as well as horse serum. EGFP hiPSCs-derived myogenic progenitors were engrafted into mdx mice via both intramuscular and intravenous injection. The restoration of dystrophin expression, the ratio of central nuclear myofibers, and the transplanted cells-derived satellite cells were accessed after intramuscular and systemic transplantation.

RESULTS

We report that abundant myogenic progenitors can be generated from hiPSCs after treatment with these three small molecules, with consequent terminal differentiation giving rise to mature myotubes in vitro. Upon intramuscular or systemic transplantation into mdx mice, these myogenic progenitors engrafted and contributed to human-derived myofiber regeneration in host muscles, restored dystrophin expression, ameliorated pathological lesions, and seeded the satellite cell compartment in dystrophic muscles.

CONCLUSIONS

This study demonstrates the muscle regeneration potential of myogenic progenitors derived from hiPSCs using non-transgenic induction methods. Engraftment of hiPSC-derived myogenic progenitors could be a potential future therapeutic strategy to treat DMD in a clinical setting.

Authors+Show Affiliations

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, Guangdong, China.Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, Guangdong, China.Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, Guangdong, China.Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. zhuyling3@mail.sysu.edu.cn. Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, Guangdong, China. zhuyling3@mail.sysu.edu.cn.Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. chengzhang100@foxmail.com. Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, Guangdong, China. chengzhang100@foxmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32430065

Citation

He, Ruojie, et al. "Engraftment of Human Induced Pluripotent Stem Cell-derived Myogenic Progenitors Restores Dystrophin in Mice With Duchenne Muscular Dystrophy." Biological Research, vol. 53, no. 1, 2020, p. 22.
He R, Li H, Wang L, et al. Engraftment of human induced pluripotent stem cell-derived myogenic progenitors restores dystrophin in mice with duchenne muscular dystrophy. Biol Res. 2020;53(1):22.
He, R., Li, H., Wang, L., Li, Y., Zhang, Y., Chen, M., Zhu, Y., & Zhang, C. (2020). Engraftment of human induced pluripotent stem cell-derived myogenic progenitors restores dystrophin in mice with duchenne muscular dystrophy. Biological Research, 53(1), 22. https://doi.org/10.1186/s40659-020-00288-1
He R, et al. Engraftment of Human Induced Pluripotent Stem Cell-derived Myogenic Progenitors Restores Dystrophin in Mice With Duchenne Muscular Dystrophy. Biol Res. 2020 May 19;53(1):22. PubMed PMID: 32430065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Engraftment of human induced pluripotent stem cell-derived myogenic progenitors restores dystrophin in mice with duchenne muscular dystrophy. AU - He,Ruojie, AU - Li,Huan, AU - Wang,Liang, AU - Li,Yaqin, AU - Zhang,Yu, AU - Chen,Menglong, AU - Zhu,Yuling, AU - Zhang,Cheng, Y1 - 2020/05/19/ PY - 2020/01/15/received PY - 2020/04/28/accepted PY - 2020/5/21/entrez PY - 2020/5/21/pubmed PY - 2020/6/18/medline KW - Duchenne muscular dystrophy KW - Human induced pluripotent stem cells KW - Muscle regeneration KW - Myogenic progenitors KW - Satellite cells SP - 22 EP - 22 JF - Biological research JO - Biol. Res. VL - 53 IS - 1 N2 - BACKGROUND: Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder with no effective treatment that is caused by the loss of dystrophin. Human induced pluripotent stem cells (hiPSCs) offer a promising unlimited resource for cell-based therapies of muscular dystrophy. However, their clinical applications are hindered by inefficient myogenic differentiation, and moreover, the engraftment of non-transgene hiPSC-derived myogenic progenitors has not been examined in the mdx mouse model of DMD. METHODS: We investigated the muscle regenerative potential of myogenic progenitors derived from hiPSCs in mdx mice. The hiPSCs were transfected with enhanced green fluorescent protein (EGFP) vector and defined as EGFP hiPSCs. Myogenic differentiation was performed on EGFP hiPSCs with supplementary of basic fibroblast growth factor, forskolin, 6-bromoindirubin-3'-oxime as well as horse serum. EGFP hiPSCs-derived myogenic progenitors were engrafted into mdx mice via both intramuscular and intravenous injection. The restoration of dystrophin expression, the ratio of central nuclear myofibers, and the transplanted cells-derived satellite cells were accessed after intramuscular and systemic transplantation. RESULTS: We report that abundant myogenic progenitors can be generated from hiPSCs after treatment with these three small molecules, with consequent terminal differentiation giving rise to mature myotubes in vitro. Upon intramuscular or systemic transplantation into mdx mice, these myogenic progenitors engrafted and contributed to human-derived myofiber regeneration in host muscles, restored dystrophin expression, ameliorated pathological lesions, and seeded the satellite cell compartment in dystrophic muscles. CONCLUSIONS: This study demonstrates the muscle regeneration potential of myogenic progenitors derived from hiPSCs using non-transgenic induction methods. Engraftment of hiPSC-derived myogenic progenitors could be a potential future therapeutic strategy to treat DMD in a clinical setting. SN - 0717-6287 UR - https://www.unboundmedicine.com/medline/citation/32430065/Engraftment_of_human_induced_pluripotent_stem_cell_derived_myogenic_progenitors_restores_dystrophin_in_mice_with_duchenne_muscular_dystrophy_ L2 - https://biolres.biomedcentral.com/articles/10.1186/s40659-020-00288-1 DB - PRIME DP - Unbound Medicine ER -