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Cited by 110Mesenchymal stem cell researchLiver physiology and pathologyTissue Engineering and Regenerative Medicine

Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver regeneration in a rat massive hepatectomy model

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Yu, Jun, Yin, Shengyong, Zhang, Wu, Gao, Feng, Liu, Yuanxing, Chen, Zhiyun, Zhang, Min, He, Jiangjuan +1 more·2013·Stem Cell Research & Therapy
DOI 10.1186/scrt234PMC PMC3854783
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Abstract

Introduction: Bone marrow mesenchymal stem cells (BMMSCs) have been reported to facilitate liver regeneration after toxic injuries. However, the effect of BMMSCs on liver regeneration after massive hepatectomy is barely studied. Here we explored whether infusion of BMMSCs promotes liver regeneration in a rat massive hepatectomy model. Methods: Hypoxia preconditioning was achieved by culturing BMMSCs under a hypoxia environment. Then 85% hepatectomy was performed and hypoxia or normoxia preconditioned BMMSCs were infused into the portal vein. A group of rats received vascular endothelial growth factor (VEGF) neutralizing antibody perioperatively, and underwent 85% hepatectomy and a subsequent infusion of hypoxia preconditioned BMMSCs to verify the role of VEGF in the effects of BMMSCs on liver regeneration. Liver samples were collected and liver regeneration was evaluated postoperatively. Results: Hypoxia preconditioning enhanced the expression of VEGF in BMMSCs in vitro. Infusion of BMMSCs promoted proliferation of hepatocytes, reflected by elevated cyclin D 1 expression and proliferating cell nuclear antigen-positive hepatocytes. However, BMMSC infusion did not improve the serum albumin level, liver weight/body weight ratio, and survival after operation. Infusion of hypoxia preconditioned BMMSCs significantly elevated cyclin D 1, proliferating cell nuclear antigen-positive hepatocytes, liver weight/body weight ratio, and survival compared with normoxia preconditioned BMMSCs, accompanied by an increased serum albumin level. The level of VEGF in liver homogenate was much higher in hypoxia preconditioned BMMSC-treated animals than in other groups. In addition, the perioperative injection of VEGF neutralizing antibody significantly blocked the therapeutic effects of hypoxia preconditioned BMMSCs on liver injury and regeneration in this model. Conclusion: Hypoxia preconditioned BMMSCs enhanced liver regeneration after massive hepatectomy in rats, possibly by upregulating the level of VEGF.

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  • Hypoxia preconditioning in BM-MSCs facilitated liver regeneration after 85% hepatectomy in rat models, with significantly increased cyclin D1, VEGF, PCNA-positive hepatocytes, liver weight/body weight ratio, serum albumin levels and cell survival.

    “hypoxia preconditioning in BM-MSCs was demonstrated to facilitate liver regeneration after 85 % hepatectomy in rat models, with a significant increased cyclin D1, VEGF, PCNA-positive hepatocytes, liver weight/body weight ratio, serum albumin levels and cell survival [125].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [125]

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Cited by

Sorted by citations

Authors
Yu, J., Yin, S., Zhang, W., Gao, F., Liu, Y., Chen, Z., Zhang, M., He, J., & Zheng, S.
Affiliations
First Affiliated Hospital Zhejiang University (CN)
Corresponding author
Zheng, Shusen
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2013-07-15
Volume
4
Issue
4
Pages
83-83
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/scrt234
PMC
PMC3854783
OpenAlex
W2095618136
Cited by
110
References
2
Citations by year
2026: 1 · 2025: 3 · 2024: 11 · 2023: 10 · 2022: 5 · 2021: 13 · 2020: 5 · 2019: 5 · 2018: 12 · 2017: 11 · 2016: 11 · 2015: 16 · 2014: 6 · 2013: 1
FWCI
5.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (2012AA021002)
  • Natural Science Foundation of Zhejiang Province
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
bone marrow mesenchymal stem cells, hypoxic preconditioning, liver regeneration, massive hepatectomy, vascular endothelial growth factor, hepatocyte proliferation, cyclin D1, VEGF neutralizing antibody, stem cell transplantation, portal vein infusion
MeSH terms
Animals, Bone Marrow Cells, Disease Models, Animal, Hepatectomy, Liver Regeneration, Male, Cell Hypoxia, Rats, Sprague-Dawley, Cell Proliferation, Rats, Mesenchymal Stem Cells

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