Cellular Antioxidant Levels Influence Muscle Stem Cell Therapy
Open accessAbstract
Although cellular transplantation has been shown to promote improvements in cardiac function following injury, poor cell survival following transplantation continues to limit the efficacy of this therapy. We have previously observed that transplantation of muscle-derived stem cells (MDSCs) improves cardiac function in an acute murine model of myocardial infarction to a greater extent than myoblasts. This improved regenerative capacity of MDSCs is linked to their increased level of antioxidants such as glutathione (GSH) and superoxide dismutase. In the current study, we demonstrated the pivotal role of antioxidant levels on MDSCs survival and cardiac functional recovery by either reducing the antioxidant levels with diethyl maleate or increasing antioxidant levels with N-acetylcysteine (NAC). Both the anti- and pro-oxidant treatments dramatically influenced the survival of the MDSCs in vitro. When NAC-treated MDSCs were transplanted into infarcted myocardium, we observed significantly improved cardiac function, decreased scar tissue formation, and increased numbers of CD31(+) endothelial cell structures, compared to the injection of untreated and diethyl maleate-treated cells. These results indicate that elevating the levels of antioxidants in MDSCs with NAC can significantly influence their tissue regeneration capacity.
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NAC improves survival of a distinct population of myogenic stem cells in skeletal muscle in vitro and in vivo.
“also improves survival of a distinct population of myogenic stem cells in skeletal muscle, both in vitro and in vivo34.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [34]
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References 50 · Cited by 94
- Authors
- Drowley, L., Okada, M., Beckman, S., Vella, J., Keller, B., Tobita, K., & Huard, J.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Huard, Johnny
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 18
- Issue
- 10
- Pages
- 1865-1873
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC2951566
- OpenAlex
- W2009992574
- Cited by
- 94
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 12 · 2014: 7 · 2013: 7 · 2012: 14
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- Funders
- National Institutes of Health (5u54ar050733-06)
- National Institute on Aging (P30AG024827)
- National Heart, Lung, and Blood Institute (R01HL069368, #HL069368)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (IU54AR050733-01, U54-AR050733)
- National Institute of Biomedical Imaging and Bioengineering (T32EB001026)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- muscle-derived stem cells, antioxidant levels, N-acetylcysteine, diethyl maleate, glutathione, superoxide dismutase, cell survival, myocardial infarction, cardiac regeneration, stem cell transplantation, scar formation, cardiac function recovery
- MeSH terms
- Acetylcysteine, Animals, Antioxidants, Cell Differentiation, Cell Survival, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Male, Maleates, Mice, Inbred C57BL, Myocardial Infarction, Stem Cells, Blotting, Western, Mice, SCID, Apoptosis, Muscle, Skeletal, Platelet Endothelial Cell Adhesion Molecule-1, Vascular Endothelial Growth Factor A, Endothelial Cells, Cell Proliferation, Mice, Cell- and Tissue-Based Therapy
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