scholarly journals Production of Innervated Skeletal Muscle Fibers Using Human Induced Pluripotent Stem Cells

2020 ◽  
Author(s):  
Mégane Delourme ◽  
Natacha Broucqsault ◽  
Kilian Mazaleyrat ◽  
Frédérique Magdinier
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Muscle Fibers ◽  
Skeletal Muscle Fibers ◽  
Induced Pluripotent

scholarly journals Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency

Stem Cells ◽  
2017 ◽  
Vol 35 (7) ◽  
pp. 1687-1703 ◽  
Author(s):  
Damià Romero-Moya ◽  
Carlos Santos-Ocaña ◽  
Julio Castaño ◽  
Gloria Garrabou ◽  
José A. Rodríguez-Gómez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Coenzyme Q10 ◽  
Pluripotent Stem Cells ◽  
Genetic Rescue ◽  
Induced Pluripotent ◽  
Muscle Impairment

scholarly journals Multilineage Differentiation for Formation of Innervated Skeletal Muscle Fibers from Healthy and Diseased Human Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1531 ◽  
Author(s):  
Kilian Mazaleyrat ◽  
Cherif Badja ◽  
Natacha Broucqsault ◽  
Raphaël Chevalier ◽  
Camille Laberthonnière ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscular Dystrophy ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Disease Modeling ◽  
Muscle Fibers ◽  
Functional Evaluation ◽  
Skeletal Muscle Fibers ◽  
Human Ipscs

Induced pluripotent stem cells (iPSCs) obtained by reprogramming primary somatic cells have revolutionized the fields of cell biology and disease modeling. However, the number protocols for generating mature muscle fibers with sarcolemmal organization using iPSCs remain limited, and partly mimic the complexity of mature skeletal muscle. Methods: We used a novel combination of small molecules added in a precise sequence for the simultaneous codifferentiation of human iPSCs into skeletal muscle cells and motor neurons. Results: We show that the presence of both cell types reduces the production time for millimeter-long multinucleated muscle fibers with sarcolemmal organization. Muscle fiber contractions are visible in 19–21 days, and can be maintained over long period thanks to the production of innervated multinucleated mature skeletal muscle fibers with autonomous cell regeneration of PAX7-positive cells and extracellular matrix synthesis. The sequential addition of specific molecules recapitulates key steps of human peripheral neurogenesis and myogenesis. Furthermore, this organoid-like culture can be used for functional evaluation and drug screening. Conclusion: Our protocol, which is applicable to hiPSCs from healthy individuals, was validated in Duchenne Muscular Dystrophy, Myotonic Dystrophy, Facio-Scapulo-Humeral Dystrophy and type 2A Limb-Girdle Muscular Dystrophy, opening new paths for the exploration of muscle differentiation, disease modeling and drug discovery.

scholarly journals Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance

2016 ◽  
Vol 113 (7) ◽  
pp. 1889-1894 ◽  
Author(s):  
Salvatore Iovino ◽  
Alison M. Burkart ◽  
Laura Warren ◽  
Mary Elizabeth Patti ◽  
C. Ronald Kahn
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ips Cells ◽  
Muscle Insulin Resistance ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPS cells) represent a unique tool for the study of the pathophysiology of human disease, because these cells can be differentiated into multiple cell types in vitro and used to generate patient- and tissue-specific disease models. Given the critical role for skeletal muscle insulin resistance in whole-body glucose metabolism and type 2 diabetes, we have created a novel cellular model of human muscle insulin resistance by differentiating iPS cells from individuals with mutations in the insulin receptor (IR-Mut) into functional myotubes and characterizing their response to insulin in comparison with controls. Morphologically, IR-Mut cells differentiated normally, but had delayed expression of some muscle differentiation-related genes. Most importantly, whereas control iPS-derived myotubes exhibited in vitro responses similar to primary differentiated human myoblasts, IR-Mut myotubes demonstrated severe impairment in insulin signaling and insulin-stimulated 2-deoxyglucose uptake and glycogen synthesis. Transcriptional regulation was also perturbed in IR-Mut myotubes with reduced insulin-stimulated expression of metabolic and early growth response genes. Thus, iPS-derived myotubes from individuals with genetically determined insulin resistance demonstrate many of the defects observed in vivo in insulin-resistant skeletal muscle and provide a new model to analyze the molecular impact of muscle insulin resistance.

scholarly journals Extracellular Vesicles from Skeletal Muscle Cells Efficiently Promote Myogenesis in Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1527 ◽  
Author(s):  
Denisa Baci ◽  
Maila Chirivì ◽  
Valentina Pace ◽  
Fabio Maiullari ◽  
Marika Milan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Extracellular Vesicles ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Bioactive Molecules ◽  
Patient Specific ◽  
Induced Pluripotent

The recent advances, offered by cell therapy in the regenerative medicine field, offer a revolutionary potential for the development of innovative cures to restore compromised physiological functions or organs. Adult myogenic precursors, such as myoblasts or satellite cells, possess a marked regenerative capacity, but the exploitation of this potential still encounters significant challenges in clinical application, due to low rate of proliferation in vitro, as well as a reduced self-renewal capacity. In this scenario, induced pluripotent stem cells (iPSCs) can offer not only an inexhaustible source of cells for regenerative therapeutic approaches, but also a valuable alternative for in vitro modeling of patient-specific diseases. In this study we established a reliable protocol to induce the myogenic differentiation of iPSCs, generated from pericytes and fibroblasts, exploiting skeletal muscle-derived extracellular vesicles (EVs), in combination with chemically defined factors. This genetic integration-free approach generates functional skeletal myotubes maintaining the engraftment ability in vivo. Our results demonstrate evidence that EVs can act as biological “shuttles” to deliver specific bioactive molecules for a successful transgene-free differentiation offering new opportunities for disease modeling and regenerative approaches.

Generation of skeletal muscle stem/progenitor cells from murine induced pluripotent stem cells

2010 ◽  
Vol 24 (7) ◽  
pp. 2245-2253 ◽  
Author(s):  
Yuta Mizuno ◽  
Hsi Chang ◽  
Katsutsugu Umeda ◽  
Akira Niwa ◽  
Toru Iwasa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals Induction of Skeletal Muscle Progenitors and Stem Cells from human induced Pluripotent Stem Cells

2020 ◽  
Vol 7 (4) ◽  
pp. 395-405
Author(s):  
Takahiko Sato
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Induced Pluripotent ◽  
Myogenic Induction

Induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells and tissues including skeletal muscle. The approach to convert these stem cells into skeletal muscle cells offers hope for patients afflicted with skeletal muscle diseases such as Duchenne muscular dystrophy (DMD). Several methods have been reported to induce myogenic differentiation with iPSCs derived from myogenic patients. An important point for generating skeletal muscle cells from iPSCs is to understand in vivo myogenic induction in development and regeneration. Current protocols of myogenic induction utilize techniques with overexpression of myogenic transcription factors such as Myod1(MyoD), Pax3, Pax7, and others, using recombinant proteins or small molecules to induce mesodermal cells followed by myogenic progenitors, and adult muscle stem cells. This review summarizes the current approaches used for myogenic induction and highlights recent improvements.

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