Evaluation of the Therapeutic Potential of Human iPSCs in a Murine Model of VML
| Autor: | Nadine Matthias, Jianbo Wu, Radbod Darabi, Shubhang Bhalla |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Induced Pluripotent Stem Cells
Biology Neuromuscular junction Fibrin Contractility 03 medical and health sciences Mice 0302 clinical medicine Immune system Muscular Diseases Drug Discovery Genetics medicine Animals Progenitor cell Induced pluripotent stem cell Muscle Skeletal Molecular Biology 030304 developmental biology Pharmacology 0303 health sciences Graft Survival Cell biology Disease Models Animal medicine.anatomical_structure Treatment Outcome 030220 oncology & carcinogenesis biology.protein Molecular Medicine Original Article Stem cell PAX7 Atrophy Stem Cell Transplantation |
| Zdroj: | Mol Ther |
| ISSN: | 1525-0024 |
| Popis: | Volumetric muscle loss injury is a common health problem with long-term disabilities. One common treatment is using muscle flaps from donor site, which has limited potentials due to donor site availability and morbidity. Although several stem cell therapies have been evaluated so far, most suffer from limited availability, immune incompatibility, or differentiation potential. Therefore, induced pluripotent stem cells (iPSCs) have a great promise for this purpose due to their unique differentiation, self-renewal, and immunocompatibility. Current study was designed to determine therapeutic potential of human iPSCs (hiPSCs) in a mouse model of volumetric muscle loss. Muscles were subjected to excision to generate 30%–40% muscle loss. Next, hiPSCs were differentiated toward skeletal myogenic progenitors and used with fibrin hydrogel to reconstruct the lost muscle. Histologic evaluation of the treated muscles indicated abundant engraftment of donor-derived mature fibers expressing human markers. Donor-derived fibers were also positive for the presence of neuromuscular junction (NMJ), indicating their proper innervation. Evaluation of the engrafted region indicated the presence of donor-derived satellite cells expressing human markers and Pax7. Finally, in situ muscle function analysis demonstrated significant improvement of the muscle contractility in muscles treated with hiPSCs. These results therefore provide key evidence for the therapeutic potential of human iPSCs in volumetric muscle loss injuries. |
| Databáze: | OpenAIRE |
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