Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury
Abstract
Bone-marrow-derived human MSCs (mesenchymal stem cells) support repair when administered to animals with TBI (traumatic brain injury) in large part through secreted trophic factors. We directly tested the ability of the culture medium (or secretome) collected from human MSCs under normoxic or hypoxic conditions to protect neurons in a rat model of TBI. Concentrated conditioned medium from cultured human MSCs or control medium was infused through the tail vein of rats subjected to TBI. We have demonstrated that MSCs cultured in hypoxia were superior to those cultured in normoxia in inducing expression of both HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) in the cultured medium. We showed further that rats treated with the secretome from both normoxic- and hypoxic-preconditioned MSCs performed significantly better than the controls in both motor and cognitive functional test. Subsequent post-mortem evaluation of brain damage at the 4-day time point confirmed that both normoxic- and hypoxic-preconditioned MSC secretome-treated rats had significantly greater numbers of newly forming neurons, but significantly less than the controls in brain damaged volume and apoptosis. The TBI rats treated with hypoxic-preconditioned MSC secretome performed significantly better in both motor and cognitive function tests and neurogenesis, and had significantly less brain damage than the TBI rats treated with the normoxic-preconditioned MSC secretome. Collectively, these findings suggest that MSCs secrete bioactive factors, including HGF and VEGF, that stimulate neurogenesis and improve outcomes of TBI in a rat model. Hypoxic preconditioning enhances the secretion of these bioactive factors from the MSCs and the therapeutic potential of the cultured MSC secretome in experimental TBI.
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A large number of studies demonstrated that MSCs cultured in hypoxia exhibit higher rates of proliferation and better retain their stem cell properties.
“A large number of studies demonstrated that MSCs cultured in hypoxia exhibit higher rates of proliferation and better retain their stem cell properties [25, 30–33].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [32]
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Self-citation
- Authors
- Chang, C.-P., Chio, C.-C., Cheong, C.-U., Chao, C.-M., Cheng, B.-C., & Lin, M.-T.
- Affiliations
- Southern Taiwan University of Science and Technology (TW)
- Chi Mei Medical Center (TW)
- Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
- Corresponding author
- Chio, Chung-Ching
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2012-10-05
- Volume
- 124
- Issue
- 3
- Pages
- 165-176
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W2002620928
- Cited by
- 287
- References
- 36
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 19 · 2023: 20 · 2022: 24 · 2021: 25 · 2020: 29 · 2019: 25 · 2018: 23 · 2017: 22 · 2016: 19 · 2015: 28 · 2014: 17 · 2013: 17
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- mesenchymal stem cells, hypoxic preconditioning, traumatic brain injury, secretome, conditioned medium, hepatocyte growth factor, vascular endothelial growth factor, neurogenesis, neuroprotection, stem cell therapy, apoptosis
- MeSH terms
- Animals, Avoidance Learning, Bone Marrow Cells, Brain, Brain Injuries, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Humans, Male, Motor Activity, Neurons, Cell Hypoxia, Culture Media, Conditioned, Rats, Sprague-Dawley, Apoptosis, Hepatocyte Growth Factor, Vascular Endothelial Growth Factor A, Rats, Neurogenesis, Mesenchymal Stem Cells
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