Dataset Information

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.

ABSTRACT: It is still unclear if immune responses will compromise the large-scale utilization of human induced pluripotent stem cells (hiPSCs)-derived cell therapies. To answer this question, we used humanized mouse models generated by the adoptive transfer of peripheral blood mononuclear cells or the cotransplantation of hematopoietic stem cells and human thymic tissue. Using these mice, we evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or differentiated from hiPSCs or fibroblasts. Our results showed that while allogeneic grafts were mostly rejected and highly infiltrated with human T?cells, engraftment of autologous cells was tolerated. We also observed that hiPSC-derived myogenic progenitor cells (MPCs) are not targeted by autologous T?cells and natural killer cells in?vitro. These findings suggest that the reprogramming and differentiation procedures we used are not immunogenic and that hiPSC-derived MPCs will be tolerated in the presence of a competent human immune system.

SUBMITTER: Benabdallah B

PROVIDER: S-EPMC7848353 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.

Benabdallah Basma B Désaulniers-Langevin Cynthia C Goyer Marie-Lyn ML Colas Chloé C Maltais Chantale C Li Yuanyi Y Guimond Jean V JV Tremblay Jacques P JP Haddad Elie E Beauséjour Christian C

Stem cells translational medicine 20200902 2

It is still unclear if immune responses will compromise the large-scale utilization of human induced pluripotent stem cells (hiPSCs)-derived cell therapies. To answer this question, we used humanized mouse models generated by the adoptive transfer of peripheral blood mononuclear cells or the cotransplantation of hematopoietic stem cells and human thymic tissue. Using these mice, we evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or different ...[more]

PMID: 32881406

Similar Datasets

Project description:BackgroundDuchenne 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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.

Dataset Information

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.

Publications

Myogenic progenitor cells derived from human induced pluripotent stem cell are immune-tolerated in humanized mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets