Characterization of hiPSC-Derived Muscle Progenitors Reveals Distinctive Markers for Myogenic Cell Purification Toward Cell Therapy

Nalbandian, Minas; Zhao, Mingming; Sasaki-Honda, Mitsuru; Jonouchi, Tatsuya; Lucena-Cacace, Antonio; Mizusawa, Takuma; Yasuda, Masahiko; Yoshida, Yoshinori; Hotta, Akitsu; Sakurai, Hiroyuki

doi:10.1016/j.stemcr.2021.03.004

Cited by 30 publications

(47 citation statements)

References 52 publications

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“…Pax3/7 or MyoD) [ 32 , 33 ] sometimes together with epigenetic modulators (e.g. BRG1/BRM-associated factor 60 (BAF60) or Jumonji domain-containing protein D3 (JMJD3)) [ 34 , 35 ] and 2) transgene-free methods which use a cocktail of signalling molecules, growth factors and inhibitors to recapitulate developmental myogenesis [ 36 , 37 , 38 , 39 ].…”

Section: Cellular Constituents Of Advanced Human Muscle Models: Beyond Primary Myoblastsmentioning

confidence: 99%

Advanced models of human skeletal muscle differentiation, development and disease: Three-dimensional cultures, organoids and beyond

Jalal

Dastidar

Tedesco

2021

Current Opinion in Cell Biology

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Advanced in vitro models of human skeletal muscle tissue are increasingly needed to model complex developmental dynamics and disease mechanisms not recapitulated in animal models or in conventional monolayer cell cultures. There has been impressive progress towards creating such models by using tissue engineering approaches to recapitulate a range of physical and biochemical components of native human skeletal muscle tissue. In this review, we discuss recent studies focussed on developing complex in vitro models of human skeletal muscle beyond monolayer cell cultures, involving skeletal myogenic differentiation from human primary myoblasts or pluripotent stem cells, often in the presence of structural scaffolding support. We conclude with our outlook on the future of advanced skeletal muscle three-dimensional cultures (e.g. organoids and biofabrication) to produce physiologically and clinically relevant platforms for disease modelling and therapy development in musculoskeletal and neuromuscular disorders.

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Section: Cellular Constituents Of Advanced Human Muscle Models: Beyond Primary Myoblastsmentioning

confidence: 99%

Advanced models of human skeletal muscle differentiation, development and disease: Three-dimensional cultures, organoids and beyond

Jalal

Dastidar

Tedesco

2021

Current Opinion in Cell Biology

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“… 67 , 68 It is unclear whether the phenotypes identified by the MyoD overexpression system can be reproduced by the stepwise induction method. Our lab recently reported induction protocols 69 , 70 by which differentiated myotubes could become more matured. Thus, this will require further detailed study to better understand the muscle fatigue phenotype using induction protocols.…”

Section: Discussionmentioning

confidence: 99%

A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs

Uchimura

Asano

Nakata

et al. 2021

Cell Reports Medicine

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Duchenne muscular dystrophy (DMD) is a muscle degenerating disease caused by dystrophin deficiency, for which therapeutic options are limited. To facilitate drug development, it is desirable to develop in vitro disease models that enable the evaluation of DMD declines in contractile performance. Here, we show MYOD1-induced differentiation of hiPSCs into functional skeletal myotubes in vitro with collagen gel and electrical field stimulation (EFS). Long-term EFS training (0.5 Hz, 20 V, 2 ms, continuous for 2 weeks) mimicking muscle overuse recapitulates declines in contractile performance in dystrophic myotubes. A screening of clinically relevant drugs using this model detects three compounds that ameliorate this decline. Furthermore, we validate the feasibility of adapting the model to a 96-well culture system using optogenetic technology for large-scale screening. Our results support a disease model using patient-derived iPSCs that allows for the recapitulation of the contractile pathogenesis of DMD and a screening strategy for drug development.

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“…S01 was generated under written consent with approval by the Kyoto University Graduate School and Faculty of Medicine Ethics Committee (approval numbers #E1762, #G567and #Rinsho71). Both S01 and 414C2 were labeled with a Venus reporter for PAX7 , and then they were differentiated into iMuSCs as previously described [ 13 , 24 ]. Briefly, the iPSCs were seeded in a Matrigel-coated 6-well plate and cultured with StemFit (AK02N, Ajinomoto) medium (1x10 4 cells/well).…”

Section: Methodsmentioning

confidence: 99%

Transplantation of human iPSC-derived muscle stem cells in the diaphragm of Duchenne muscular dystrophy model mice

et al. 2022

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Duchenne muscular dystrophy (DMD) is an intractable genetic muscular disorder characterized by the loss of DYSTROPHIN. The restoration of DYSTROPHIN is expected to be a curative therapy for DMD. Because muscle stem cells (MuSCs) can regenerate damaged myofibers with full-length DYSTROPHIN in vivo, their transplantation is being explored as such a therapy. As for the transplanted cells, primary satellite cells have been considered, but donor shortage limits their clinical application. We previously developed a protocol that differentiates induced pluripotent stem cells (iPSCs) to MuSCs (iMuSCs). To ameliorate the respiratory function of DMD patients, cell transplantation to the diaphragm is necessary but difficult, because the diaphragm is thin and rapidly moves. In the present study, we explored the transplantation of iMuSCs into the diaphragm. First, we show direct cell injection into the diaphragm of mouse was feasible. Then, to enhance the engraftment of the transplanted cells in a rapidly moving diaphragm, we mixed polymer solutions of hyaluronic acid, alginate and gelatin to the cell suspension, finding a solution of 20% dissolved hyaluronic acid and 80% dissolved gelatin improved the engraftment. Thus, we established a method for cell transplantation into mouse diaphragm and show that an injectable hyaluronic acid-gelatin solution enables the engraftment of iMuSCs in the diaphragm.

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Characterization of hiPSC-Derived Muscle Progenitors Reveals Distinctive Markers for Myogenic Cell Purification Toward Cell Therapy

Cited by 30 publications

References 52 publications

Advanced models of human skeletal muscle differentiation, development and disease: Three-dimensional cultures, organoids and beyond

Advanced models of human skeletal muscle differentiation, development and disease: Three-dimensional cultures, organoids and beyond

A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs

Transplantation of human iPSC-derived muscle stem cells in the diaphragm of Duchenne muscular dystrophy model mice

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