Cited by 36Mesenchymal stem cell researchTelomeres, Telomerase, and SenescenceHematopoietic Stem Cell Transplantation

Oxidative Status Predicts Quality in Human Mesenchymal Stem Cells

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Bertolo, Alessandro, Capossela, Simona, Fränkl, Gion, Baur, Martin, Pötzel, Tobias, Stoyanov, Jivko·2017·Stem Cell Research & Therapy

Abstract

BACKGROUND: Human bone marrow-derived mesenchymal stem cells (MSC) are adult progenitor cells with great potential for application in cell-based therapies. From a cell-based therapy perspective, there are two limitations to MSC use: (1) these therapies require large numbers of cells, and long-term expansion of MSC in vitro promotes replicative senescence; and (2) patient variability is a challenge for defining MSC quality standards for transplantation. This study aimed to determine whether low or high oxidative status of MSC correlate with changes in cell expansion and differentiation potentials. METHODS: We investigated functional aspects of mitochondria, such as cell metabolic activity indicators and expression of antioxidant enzymes. Furthermore, we tested if senescence-induced changes in oxidative status of MSC could be counteracted by methylene blue (MB), an alternative mitochondrial electron transfer known to enhance cell bioenergetics. RESULTS: MSC isolated from donors of the same age showed distinctive behavior in culture and were grouped as weak (low colony-forming units (CFU) and a short life in vitro) and vigorous MSC (high CFU and a long life in vitro). In comparison to weak MSC, vigorous MSC had oxidative status characterized by lower mitochondrial membrane potential, lower mitochondrial activity, and fewer reactive oxygen species production, as well as reduced mitochondrial biogenesis. Vigorous MSC had a significantly higher expansion potential compared to weak MSC, while no differences were observed during differentiation. MB treatment significantly improved expansion and differentiation potential, however only in vigorous MSC. CONCLUSIONS: Together, these results demonstrate the importance of mitochondrial function in MSC in vitro, and that cells with low oxidative status levels are better candidates for cell-based therapies.

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  • Methylene blue may also prevent senescence and OS in primary retinal ganglion cells and mesenchymal stem cells, but its efficacy on stem cells remains limited to the cellular fraction characterized by a lower baseline level of OS.

    “Besides skin aging, MB may also prevent senescence and OS in other cell types, such as primary retinal ganglion cells and mesenchymal stem cells (MSCs), but its efficacy on stem cells remains limited to the cellular fraction characterized by a lower baseline level of OS [81,82].”
  • Antioxidants efficacy might depend upon oxidative stress levels.

    “Besides the dosage, a careful evaluation of the optimal administration window can be also crucial to achieve a clinical benefit as antioxidants efficacy might depend upon OS levels [81].”

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Authors
Bertolo, A., Capossela, S., Fränkl, G., Baur, M., Pötzel, T., & Stoyanov, J.
Affiliations
  • Swiss Paraplegic Research (CH)
  • Swiss Paraplegic Center (CH)
  • Luzerner Kantonsspital (CH)
  • University of Bern (CH)
Corresponding author
Stoyanov, Jivko
Venue
Stem Cell Research & Therapy
Published
2017-01-06
Volume
8
Issue
1
Pages
3-3
ISSN
1757-6512 (ISSN-L)
OpenAlex
W2569783565
Cited by
36
References
46
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 3
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CR32I3_140717)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
mesenchymal stem cells, oxidative status, replicative senescence, mitochondrial function, methylene blue, mitochondrial biogenesis, reactive oxygen species, mitochondrial membrane potential, differentiation potential, cell therapy, donor variability, antioxidant enzymes, colony-forming units
MeSH terms
Aged, Cell Differentiation, Cell Division, Cells, Cultured, Flow Cytometry, Humans, Male, Methylene Blue, Mitochondria, Oxidation-Reduction, Superoxides, Biomarkers, Cell Proliferation, Mesenchymal Stem Cells

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