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Pluripotent Stem Cells and Skeletal Muscle Regeneration

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Special Issue Information
Keywords
Published Papers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (10 November 2023) | Viewed by 7617

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Special Issue Editor

Dr. Sunny S. K. Chan

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Guest Editor

Department of Pediatrics, University of Minnesota, Twin Cities, Minneapolis, MN, USA
Interests: skeletal muscle regeneration; pluripotent stem cells

Special Issue Information

Dear Colleagues,

Skeletal muscle accounts for one-half of the body mass and debilitating injuries and diseases of the musculoskeletal system are common. Skeletal muscle is capable of complete regeneration due to the presence of muscle stem cells (also known as satellite cells) that reside in muscle fibers and adjacent tissues. However, in severe myopathic diseases and volumetric muscle loss, this regenerative capacity is exhausted. The advent of pluripotent stem cell technology promises the generation of many clinically relevant and difficult-to-obtain cell types for cellular therapies, including skeletal myogenic progenitors. Indeed, for the past decade or so, there has been a growing interest in developing regenerative approaches to replace injured or diseased muscles with healthy self-renewing myogenic progenitors. In this Special Issue, we welcome studies that will advance our knowledge on the use of pluripotent stem cells for skeletal muscle regeneration. Our goal is to facilitate dialogue among researchers and other stakeholders and to bring regenerative medicine for treating skeletal muscle diseases one step closer to reality.

Dr. Sunny S. K. Chan
Guest Editor

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Keywords

pluripotent stem cells
skeletal muscle regeneration
myogenic differentiation
muscle development
induced pluripotent stem cells
embryonic stem cells
cell therapies
regenerative medicine

Published Papers (4 papers)

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Research

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16 pages, 4638 KiB

Open AccessArticle

Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors

by Phablo Abreu, Bayardo I. Garay, Travis Nemkov, Aline M. S. Yamashita and Rita C. R. Perlingeiro

Cells 2024, 13(1), 76; https://doi.org/10.3390/cells13010076 - 29 Dec 2023

Cited by 1 | Viewed by 1091

Abstract

In vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting that engrafted PSC-derived myogenic cells remodel their transcriptional signature upon interaction within the adult muscle environment. Here, we show that engrafted myogenic progenitors also remodel their metabolic state. Assessment of oxygen consumption revealed that exposure to the adult muscle environment promotes overt changes in mitochondrial bioenergetics, as shown by the substantial suppression of energy requirements in re-isolated iPax3 donor-derived satellite cells compared to their in vitro-generated progenitors. Mass spectrometry-based metabolomic profiling further confirmed the relationship of engrafted iPax3 donor-derived cells to adult satellite cells. The fact that in vitro-generated myogenic progenitors remodel their bioenergetic signature upon in vivo exposure to the adult muscle environment may have important implications for therapeutic applications. Full article

(This article belongs to the Special Issue Pluripotent Stem Cells and Skeletal Muscle Regeneration)

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18 pages, 2846 KiB

Open AccessArticle

Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells

by June Baik, Carolina Ortiz-Cordero, Alessandro Magli, Karim Azzag, Sarah B. Crist, Aline Yamashita, James Kiley, Sridhar Selvaraj, Ricardo Mondragon-Gonzalez, Elizabeth Perrin, John P. Maufort, Jody L. Janecek, Rachael M. Lee, Laura Hocum Stone, Parthasarathy Rangarajan, Sabarinathan Ramachandran, Melanie L. Graham and Rita C. R. Perlingeiro

Cells 2023, 12(8), 1147; https://doi.org/10.3390/cells12081147 - 13 Apr 2023

Cited by 2 | Viewed by 2266

Abstract

Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution, and immune response. While the generation of human-induced PS (iPS)-cell-derived myogenic progenitors is well established, there have been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage. Here, we report the generation of three independent Macaca fascicularis iPS cell lines and their myogenic differentiation using PAX7 conditional expression. The whole-transcriptome analysis confirmed the successful sequential induction of mesoderm, paraxial mesoderm, and myogenic lineages. NHP myogenic progenitors efficiently gave rise to myotubes under appropriate in vitro differentiation conditions and engrafted in vivo into the TA muscles of NSG and FKRP-NSG mice. Lastly, we explored the preclinical potential of these NHP myogenic progenitors in a single wild-type NHP recipient, demonstrating engraftment and characterizing the interaction with the host immune response. These studies establish an NHP model system through which iPS-cell-derived myogenic progenitors can be studied. Full article

(This article belongs to the Special Issue Pluripotent Stem Cells and Skeletal Muscle Regeneration)

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13 pages, 3830 KiB

Open AccessArticle

Efficient Muscle Regeneration by Human PSC-Derived CD82⁺ ERBB3⁺ NGFR⁺ Skeletal Myogenic Progenitors

by Ning Xie, Sabrina N. Chu, Cassandra B. Schultz and Sunny S. K. Chan

Cells 2023, 12(3), 362; https://doi.org/10.3390/cells12030362 - 18 Jan 2023

Cited by 2 | Viewed by 1852

Abstract

Differentiation of pluripotent stem cells (PSCs) is a promising approach to obtaining large quantities of skeletal myogenic progenitors for disease modeling and cell-based therapy. However, generating skeletal myogenic cells with high regenerative potential is still challenging. We recently reported that skeletal myogenic progenitors generated from mouse PSC-derived teratomas possess robust regenerative potency. We have also found that teratomas derived from human PSCs contain a skeletal myogenic population. Here, we showed that these human PSC-derived skeletal myogenic progenitors had exceptional engraftability. A combination of cell surface markers, CD82, ERBB3, and NGFR enabled efficient purification of skeletal myogenic progenitors. These cells expressed PAX7 and were able to differentiate into MHC+ multinucleated myotubes. We further discovered that these cells are expandable in vitro. Upon transplantation, the expanded cells formed new dystrophin⁺ fibers that reconstituted almost ¾ of the total muscle volume, and repopulated the muscle stem cell pool. Our study, therefore, demonstrates the possibility of producing large quantities of engraftable skeletal myogenic cells from human PSCs. Full article

(This article belongs to the Special Issue Pluripotent Stem Cells and Skeletal Muscle Regeneration)

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Review

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18 pages, 2348 KiB

Open AccessReview

The Role of Supporting Cell Populations in Satellite Cell Mediated Muscle Repair

by Amanda L. Johnson, Michael Kamal and Gianni Parise

Cells 2023, 12(15), 1968; https://doi.org/10.3390/cells12151968 - 30 Jul 2023

Cited by 5 | Viewed by 1903

Abstract

Skeletal muscle has a high capacity to repair and remodel in response to damage, largely through the action of resident muscle stem cells, termed satellite cells. Satellite cells are required for the proper repair of skeletal muscle through a process known as myogenesis. Recent investigations have observed relationships between satellite cells and other cell types and structures within the muscle microenvironment. These findings suggest that the crosstalk between inflammatory cells, fibrogenic cells, bone-marrow-derived cells, satellite cells, and the vasculature is essential for the restoration of muscle homeostasis. This review will discuss the influence of the cells and structures within the muscle microenvironment on satellite cell function and muscle repair. Full article

(This article belongs to the Special Issue Pluripotent Stem Cells and Skeletal Muscle Regeneration)

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