Generation of Functional Myocytes from Equine Induced Pluripotent Stem Cells.
Abstract: Induced pluripotent stem cells (iPSCs) have revolutionized human biomedicine through their use in disease modeling and therapy. In comparison, little progress has been made toward the application of iPSCs in veterinary species. In that regard, skeletal myocytes from iPSCs would have great potential for understanding muscle function and disease in the equine athlete. In this study, we generated skeletal myotubes by transducing equine iPSC-derived mesenchymal derivatives with an inducible lentiviral vector coding for the human sequence of the myogenic factor, MyoD. Myosin heavy chain-positive myotubes generated from two different iPSC lines were compared to myotubes from adult equine skeletal muscle progenitor cells (MPCs). iPSC myotubes had a smaller mean area than MPC myotubes (≤2-fold). In addition, quantitative polymerase chain reaction analyses showed that iPSC myotubes expressed MYH2 and MYH3 isoforms (at similar or lower levels than MPC myotubes), but they did not express the mature muscle isoform, MYH1. Compared to MPC myotubes, iPSC myotubes expressed reduced levels of the myogenic factors, MYOD1 and MYF6, but did not express MYF5. Finally, iPSC myotubes responded to KCl-induced membrane depolarization by releasing calcium and did so in a manner similar to MPC myotubes. In conclusion, this is the first study to report the generation of functional myocytes from equine iPSCs.
Publication Date: 2018-09-12 PubMed ID: 30207795PubMed Central: PMC6166488DOI: 10.1089/cell.2018.0023Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study focuses on the creation of functional muscle cells (myocytes) from horse-derived stem cells (also known as Equine Induced Pluripotent Stem Cells) and is regarded as a significant stride towards understanding muscle function and potential diseases in horses.
Introduction
- The current research revolves around Induced Pluripotent Stem Cells (iPSCs) that have brought about a revolution in human biomedicine due to their application in disease modeling and therapy.
- However, their application in veterinary species hasn’t seen much progress, hence this research attempts to use these iPSCs to generate skeletal muscle cells, which could be a significant leap in understanding muscle function and diseases in horses.
Method
- The researchers induced skeletal muscle tube formation by transducing horse-derived iPSC mesenchymal derivatives using a lentiviral vector that codes for the human sequence of the muscle-forming factor, MyoD.
- They then compared these iPSC-created myotubes with myotubes developed from adult horse skeletal muscle progenitor cells (MPCs).
Findings
- The myotubes generated from iPSCs had a smaller mean area compared to those created from MPCs (≤2-fold).
- Quantitative polymerase chain reaction analyses revealed that the iPSC myotubes expressed MYH2 and MYH3 isoforms at levels comparable or lower than the MPC myotubes, but they didn’t express the mature muscle isoform, MYH1.
- iPSC myotubes had lower levels of the muscle-forming factors, MYOD1 and MYF6, but did not express MYF5, in comparison to MPC myotubes.
- Interestingly, the iPSC myotubes responded to KCl-induced membrane depolarization by releasing calcium in a similar manner to the MPC myotubes.
Conclusion
- This research claims to be the first to report the creation of functional myocytes from horse-derived stem cells (iPSCs).
- Such study further exhibits the potential uses of iPSCs not just in human biology and medicine but also in the veterinary field.
Cite This Article
APA
Amilon KR, Cortes-Araya Y, Moore B, Lee S, Lillico S, Breton A, Esteves CL, Donadeu FX.
(2018).
Generation of Functional Myocytes from Equine Induced Pluripotent Stem Cells.
Cell Reprogram, 20(5), 275-281.
https://doi.org/10.1089/cell.2018.0023 Publication
Researcher Affiliations
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 1 The Roslin Institute and R(D)SVS, University of Edinburgh , Edinburgh, United Kingdom .
- 2 The Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh , Edinburgh, United Kingdom .
MeSH Terms
- Animals
- Cell Differentiation
- Cells, Cultured
- Horses
- Induced Pluripotent Stem Cells / cytology
- Muscle Fibers, Skeletal / cytology
- Muscle, Skeletal / cytology
Grant Funding
- BBS/E/D/20221658 / Biotechnology and Biological Sciences Research Council
- BBS/E/D/10002071 / Biotechnology and Biological Sciences Research Council
Conflict of Interest Statement
The authors declare they have no financial conflicts of interest.
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