Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (49): 8474-8480.doi: 10.3969/j.issn.2095-4344.2013.49.003

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Hypoxic preconditioning effects on the ability of bone marrow mesenchymal stem cells tolerant to ischemia and hypoxia

Xu Qiao-yan1, Xia Lin2, Wang Ji-chang3   

  1. 1 Department of Respiratory Medicine, the People’s Hospital of Laizhou, Yantai  261400, Shandong Province, China
    2 Department of Plastic Surgery, Qilu Hospital of Shandong University, Jinan  250012, Shandong Province, China
    3 Department of Plastic Surgery, the Second Hospital of Shandong University, Jinan  250033, Shandong Province, China
  • Revised:2013-09-18 Online:2013-12-03 Published:2013-12-03
  • Contact: Wang Ji-chang, M.D., Attending physician, Department of Plastic Surgery, the Second Hospital of Shandong University, Jinan 250033, Shandong Province, China wangjichangxu@163.com
  • About author:Xu Qiao-yan, Attending physician, Department of Respiratory Medicine, the People’s Hospital of Laizhou, Yantai 261400, Shandong Province, China qiaoyanx@yahoo.cn
  • Supported by:

    the National Natural Science Foundation of China for the Youth, No. 30900309*

Abstract:

BACKGROUND: According to the previous studies, it is known that bone marrow mesenchymal stem cells live in the physiological environment of lower oxygen concentration compared with the common culture concentration (20%-21%). Hypoxia can promote bone marrow mesenchymal stem cells proliferation and maintain the characteristics of differentiation potential.
OBJECTIVE: To understand the biological characteristics of bone marrow mesenchymal stem cells after hypoxic preconditioning, and search for in vitro basis for bone marrow mesenchymal stem cells therapy in vivo with hypoxic preconditioning strategy.
METHODS: After passage and inoculation, bone marrow mesenchymal stem cells were cultured in the hypoxic incubator (1% O2, 5% CO2). Bone marrow mesenchymal stem cells cultured in the normoxic incubator (20% O2, 5% CO2) served as controls.
RESULTS AND CONCLUSION: Compared with bone marrow mesenchymal stem cells cultured under normoxia (20%O2), bone marrow mesenchymal stem cells cultured under hypoxia (1% O2) began to display exponential growth phase after a longer incubation period. Hypoxia (1% O2) was not the lethal condition for bone marrow mesenchymal stem cells. Cell survival rates of both groups reduced over time, while those of bone marrow mesenchymal stem cells cultured under normoxia reduced faster (P < 0.05). Surface markers expression of bone marrow mesenchymal stem cells, including CD29(+), CD90(+), CD31(-), CD45(-), after hypoxic preconditioning did not change greatly when compared with the results before hypoxic preconditioning. The hypoxia preconditioned bone marrow mesenchymal stem cells did not differentiate into vascular endothelial cells. Hypoxia-inducible factor-1α protein expression was promoted after 24 hours to 48 hours hypoxic preconditioning, and there was significant difference between the two time points (P < 0.05). Vascular endothelial growth factor expression increased at both transcriptional and protein levels after 48 hours hypoxic preconditioning (P < 0.05). Culture under hypoxia (1% O2) does not produce a lethal effect on bone marrow mesenchymal stem cells and can be used for hypoxic preconditioning. Surface markers of bone marrow mesenchymal stem cells after 48 hours hypoxic preconditioning exhibit no great changes and the hypoxia preconditioned bone marrow mesenchymal stem cells maintain the characteristics of stemness. Hypoxic preconditioning can promote the ability of bone marrow mesenchymal stem cells to survive under hypoxia/ ischemic condition. The activation of the hypoxic response signal transduction pathway through hypoxia-inducible factor-1α may explain this.


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程


全文链接:

Key words: anoxia, mesenchymal stem cells, stem cell transplantation, cell hypoxia, oxygen

CLC Number: