Cited by 287Mesenchymal stem cell researchTraumatic Brain Injury and Neurovascular DisturbancesSpinal Cord Injury Research

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Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury

Chang, Ching-Ping, Chio, Chung-Ching, Cheong, Chong-Un, Chao, Chien-Ming, Cheng, Bor-Chieh, Lin, Mao-Tsun·2013·Clinical Science

DOI 10.1042/cs20120226

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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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Zhang, Y., Zhao, H., Su, Y., Yang, S., Kang, T., & Li, L. (2025) · Clinical Hemorheology and Microcirculation · doi:10.1177/13860291241291326
Retracted
Additional file 1 of Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats
Ishiuchi, N., Nakashima, A., Doi, S., Yoshida, K., Maeda, S., Kanai, R., Yamada, Y., Ike, T., Doi, T., Kato, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12015339
Additional file 2 of Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats
Ishiuchi, N., Nakashima, A., Doi, S., Yoshida, K., Maeda, S., Kanai, R., Yamada, Y., Ike, T., Doi, T., Kato, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12015342
Additional file 3 of Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats
Ishiuchi, N., Nakashima, A., Doi, S., Yoshida, K., Maeda, S., Kanai, R., Yamada, Y., Ike, T., Doi, T., Kato, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12015345
Additional file 1 of Infarct-preconditioning exosomes of umbilical cord mesenchymal stem cells promoted vascular remodeling and neurological recovery after stroke in rats
Ye, Y.-C., Chang, Z.-H., Wang, P., Wang, Y.-W., Liang, J., Chen, C., Wang, J.-J., Sun, H.-T., Wang, Y., & Li, X.-H. (2022) · Figshare · doi:10.6084/m9.figshare.20401183
Additional file 1 of Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway
Shi, Y., Wang, S., Zhang, W., Zhu, Y., Fan, Z., Huang, Y., Li, F., & Yang, R. (2022) · Figshare · doi:10.6084/m9.figshare.20324743
Additional file 1 of Donor heart preservation with hypoxic-conditioned medium-derived from bone marrow mesenchymal stem cells improves cardiac function in a heart transplantation model
Zhou, P., Liu, H., Liu, X., Ling, X., Xiao, Z., Zhu, P., Zhu, Y., Lu, J., & Zheng, S. (2021) · Figshare · doi:10.6084/m9.figshare.13566116
Additional file 1 of 3D printing of injury-preconditioned secretome/collagen/heparan sulfate scaffolds for neurological recovery after traumatic brain injury in rats
Liu, X.-Y., Chang, Z.-H., Chen, C., Liang, J., Shi, J.-X., Fan, X., Shao, Q., Meng, W.-W., Wang, J.-J., & Li, X.-H. (2023) · Figshare · doi:10.6084/m9.figshare.22604758
Additional file 4 of Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats
Ishiuchi, N., Nakashima, A., Doi, S., Yoshida, K., Maeda, S., Kanai, R., Yamada, Y., Ike, T., Doi, T., Kato, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12015354
Effect of bone marrow stem cell conditioned medium on amiodarone-induced submandibular salivary gland and kidney damage in male albino rats
Ahmed, E. H., Abdeen, M. A., & Saad, E. A. (2026) · BMC Oral Health · doi:10.1186/s12903-025-07542-6
Quieting the Storm: Hypoxia as a Strategy to Boost UC-MSC Therapies for Hypoxic-Ischemic Brain Lesions in Neonatal Rats
Serrenho, I., Mendes, V. M., Caramelo, I., Cardoso, C. M. P., Manadas, B. J., & Baltazar, G. (2026) · Stem Cell Reviews and Reports · doi:10.1007/s12015-026-11089-6
Attenuation of oxidative phosporylation and induction of hypoxic celle response : [alpha]-tocopherolacetate and miR-210 effects on mesenchymal stromal cells
Loncaric, D. (2019) · theses.fr (ABES) · doi:10.70675/688931baz6abdz4f1czb8adzdbf8c07ba500
Les cellules souches mésenchymateuses dérivées du tissu adipeux dans le traitement de la polyarthrite rhumatoïde : approches in vitro et in vivo
Sayegh, S. (2019) · theses.fr (ABES) · doi:10.70675/8121e62fz9318z43f3z81c5zfebc88df751c
Potency Assays for Mesenchymal Stromal Cell-Based Therapies
Tiago, A. L., Cunha, R. M. D. S., Carreira, M. C., Jang-Milligan, F., da Silva, C. L., & Fernandes‐Platzgummer, A. (2026) · Springer handbooks · doi:10.1007/978-3-032-01636-2_22
Mesenchymal stem cell-derived secretome in traumatic brain injury: Stage-specific paracrine mechanisms and translational challenges
Huang, J., Zhang, W., Huang, G., Lai, W., Huang, Q., Xia, Z., Jiang, Q., Liu, J., & Ye, X. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115935
Stimulation of Therapeutic Angiogenesis Using Amniotic Fluid Stem Cells
Mirabella, T. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1118-9_12

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
ORCID: Chang, Ching-Ping
Chio, Chung-Ching
Chao, Chien-Ming
Lin, Mao-Tsun
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
DOI: 10.1042/cs20120226
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Clinical Neurology › 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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Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury

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