Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells
Open accessAbstract
Following cultivation of distinct mesenchymal stem cell (MSC) populations derived from human umbilical cord under hypoxic conditions (between 1.5% to 5% oxygen (O 2)) revealed a 2- to 3-fold reduced oxygen consumption rate as compared to the same cultures at normoxic oxygen levels (21% O 2). A simultaneous measurement of dissolved oxygen within the culture media from 4 different MSC donors ranged from 15 μmol/L at 1.5% O 2 to 196 μmol/L at normoxic 21% O 2. The proliferative capacity of the different hypoxic MSC populations was elevated as compared to the normoxic culture. This effect was paralleled by a significantly reduced cell damage or cell death under hypoxic conditions as evaluated by the cellular release of LDH whereby the measurement of caspase3/7 activity revealed little if any differences in apoptotic cell death between the various cultures. The MSC culture under hypoxic conditions was associated with the induction of hypoxia-inducing factor-alpha (HIF-1α) and an elevated expression of energy metabolism-associated genes including GLUT-1, LDH and PDK1. Concomitantly, a significantly enhanced glucose consumption and a corresponding lactate production could be observed in the hypoxic MSC cultures suggesting an altered metabolism of these human stem cells within the hypoxic environment.
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In neurological diseases, proteomic analysis revealed that hypoxia enhances the expression of proteins associated with neuroprotection, neural survival, differentiation, and axonal and neurite growth compared to the secretome obtained from normoxia-cultured MSCs.
“proteomic analysis revealed that hypoxia enhances the expression of proteins [128], [129], [130] associated to neuroprotection, neural survival, differentiation, and axonal and neurite growth, when compared to the secretome obtained from normoxia-cultured MSCs [128].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [130]
The Results sections report increased HIF-1α protein and changes in metabolism-related gene expression in hypoxic versus normoxic umbilical cord-derived MSCs. Neither those passages nor searches for proteomic analysis, secretome, and neural-growth proteins yielded a finding about neuroprotective or neurite-growth proteins in the secretome. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThese metabolic findings are similar to those reported in other studies and are most likely attributed to a shift from aerobic respiration via oxidative phosphorylation to anaerobic respiration via glycolysis.
“These findings are similar to those reported in other studies and are most likely attributed to a shift from aerobic respiration via oxidative phosphorylation to anaerobic respiration via glycolysis [50–52].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [50]
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References 35 · Cited by 241
Research works printed but not linked: 1
- Brown MF Gratton TP Stuart JA Metabolic rate does not scale with body mass in cultured mammalian cells Am J Physiol Regul Integr Comp Physiol 2007 292 R2115 2121 17234960
- Authors
- Lavrentieva, A., Majore, I., Kasper, C., & Hass, R.
- Affiliations
- Leibniz University Hannover (DE)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Kasper, Cornelia
- Venue
- Cell Communication and Signaling
- Published
- 2010-07-16
- Volume
- 8
- Issue
- 1
- Pages
- 18-18
- ISSN
- 1478-811X (ISSN-L)
- PMC
- PMC2918620
- OpenAlex
- W2145489725
- Cited by
- 241
- References
- 35
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 12 · 2022: 14 · 2021: 18 · 2020: 21 · 2019: 14 · 2018: 15 · 2017: 18 · 2016: 19 · 2015: 15 · 2014: 18 · 2013: 15 · 2012: 10
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cell Communication and Signaling (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repository of Leibniz Universität Hannover (Leibniz Universität Hannover) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Institutional Repository of Leibniz Universität Hannover (Leibniz Universität Hannover) (submittedVersion, cc-by-nc-nd)
- Leibniz Universität Hannover (cc-by)
- Funders
- Queen's University Belfast
- Deutsche Forschungsgemeinschaft
- Queen's University
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, umbilical cord, hypoxia, oxygen consumption, cell proliferation, cell death, apoptosis, HIF-1α, energy metabolism, glucose utilization, lactic acid production, GLUT1, PDK1, LDH
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