Hypoxic three-dimensional culture microenvironment promotes proliferation of bone marrow mesenchymal stem cells through HIF-1α signaling pathway_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

TIAN Kun ,  MU Junsheng , BO Ping

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, 100029, P.R.China;

Corresponding author：

MU Junsheng, Email: wesleymu@hotmail.com

Keywords：

Hypoxic microenvironment; three-dimensional culture; poly 3-hydroxybutyrate-co-4-hydroxybutyrate; myocardial infarction; HIF-1α signaling pathway

DOI：

10.7507/1007-4848.201809010

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of hypoxic three-dimensional culture microenvironment on the proliferation of bone marrow mesenchymal stem cells and its mechanism. Methods P5 generation mouse bone marrow mesenchymal stem cells and P (3HB-co-4HB) were co-cultured under normoxic three-dimensional (20%) and hypoxic three-dimensional microenvironment (4%) respectively. After 24 hours, the proliferation of the two groups was determined by CCK-8 method. The expression of HIF-1α gene was detected by real-time quantitative PCR after 12 hours. Western blotting was used to detect the expression of HIF-1α protein after 24 hours. Results After 24 hours, the CCK-8 method showed that the OD value of the hypoxia group was significantly higher than that of the normoxia group (0.455±0.027 vs. 0.352±0.090, n=12, P<0.05). After 12 hours of hypoxic culture, the expression level of HIF-1α mRNA in the hypoxia group was significantly higher than that in the normoxia group (P<0.05). Compared with the normoxia group (0.47± 0.05), the relative expression level of HIF-1α protein in the hypoxia group (0.63±0.06) significantly increased in the Western blotting after 24 hours (n=3, P<0.05). Conclusion The hypoxic three-dimensional microenvironment can promote the proliferation of bone marrow mesenchymal stem cells, which may be related to the activation of HIF-1α signaling pathway.

Citation： TIAN Kun, MU Junsheng, BO Ping. Hypoxic three-dimensional culture microenvironment promotes proliferation of bone marrow mesenchymal stem cells through HIF-1α signaling pathway. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(4): 385-389. doi: 10.7507/1007-4848.201809010 Copy

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5.	Niu H, Mu J, Zhang J, et al. Comparative study of three types of polymer materials co-cultured with bone marrow mesenchymal stem cells for use as a myocardial patch in cardiomyocyte regeneration. J Mater Sci Mater Med, 2013, 24(6): 1535-1542.
6.	Ma YX, Mu JS, Zhang JQ, et al. Myocardial patch formation by three-dimensional 3-hydroxybutyrate-co-4-hydroxybutyrate cultured with mouse embryonic stem cells. J Biomater Tiss Eng, 2016, 6: 1-6.
7.	Choi JW, Kim KE, Lee CY, et al. Alterations in cardiomyocyte differentiation-related proteins in rat mesenchymal stem cells exposed to hypoxia. Cell Physiol Biochem, 2016, 39(4): 1595-1607.
8.	Strauer BE, Brehm M, Zeus T, et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr, 2001, 126(34-35): 932-938.
9.	Weng Y, Zhang X, Liu A, et al. The effect of allogeneic cardiac stem cells in left ventricular geometry and function in a rat model of myocardial infarction. Cardiovasc Ther, 2018, 36(1).
10.	Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet, 2003, 361(9351): 45-46.
11.	Stamm C, Kleine HD, Westphal B, et al. CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg, 2004, 52(3): 152-158.
12.	Liu C, Abedian R, Meister R, et al. Influence of perfusion and compression on the proliferation and differentiation of bone mesenchymal stromal cells seeded on polyurethane scaffolds. Biomaterials, 2012, 33(4): 1052-1064.
13.	Lv L, Ren YL, Chen JC, et al. Application of CRISPRi for prokaryotic metabolic engineering involving multiple genes, a case study: Controllable P(3HB-co-4HB) biosynthesis. Metab Eng, 2015, 29: 160-168.
14.	Saito Y, Doi Y. Microbial synthesis and properties of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in Comamonas acidovorans. Int J Biol Macromol, 1994, 16(2): 99-104.
15.	Correia C, Serra M, Espinha N, et al. Combining hypoxia and bioreactor hydrodynamics boosts induced pluripotent stem cell differentiation towards cardiomyocytes. Stem Cell Rev, 2014, 10(6): 786-801.
16.	Ng KM, Lee YK, Chan YC, et al. Exogenous expression of HIF-1 alpha promotes cardiac differentiation of embryonic stem cells. J Mol Cell Cardiol, 2010, 48(6): 1129-1137.
17.	Dai Y, Xu M, Wang Y, et al. HIF-1alpha induced-VEGF over expression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol, 2007, 42(6): 1036-1044.

1. van der Kooy D, Weiss S. Why stem cells? Science, 2000, 287(5457): 1439-1441.
2. Schwarz ER, Patterson M, Kloner RA. Cardiomyocyte transplantation——a cell replacement for repair of myocardial infarction? Z Kardiol, 1998, 87(1): 1-7.
3. Watanabe E, Smith DM Jr, Delcarpio JB, et al. Cardiomyocyte transplantation in a porcine myocardial infarction model. Cell Transplant, 1998, 7(3): 239-246.
4. Xu SJ, Mu JS, Zhang JQ, et al. In vitro three-dimensional coculturing poly3-hydroxybutyrate-co-3-hydroxyhexanoate with mouse-induced pluripotent stem cells for myocardial patch application. J Biomater Appl, 2016, 30(8): 1273-1282.
5. Niu H, Mu J, Zhang J, et al. Comparative study of three types of polymer materials co-cultured with bone marrow mesenchymal stem cells for use as a myocardial patch in cardiomyocyte regeneration. J Mater Sci Mater Med, 2013, 24(6): 1535-1542.
6. Ma YX, Mu JS, Zhang JQ, et al. Myocardial patch formation by three-dimensional 3-hydroxybutyrate-co-4-hydroxybutyrate cultured with mouse embryonic stem cells. J Biomater Tiss Eng, 2016, 6: 1-6.
7. Choi JW, Kim KE, Lee CY, et al. Alterations in cardiomyocyte differentiation-related proteins in rat mesenchymal stem cells exposed to hypoxia. Cell Physiol Biochem, 2016, 39(4): 1595-1607.
8. Strauer BE, Brehm M, Zeus T, et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr, 2001, 126(34-35): 932-938.
9. Weng Y, Zhang X, Liu A, et al. The effect of allogeneic cardiac stem cells in left ventricular geometry and function in a rat model of myocardial infarction. Cardiovasc Ther, 2018, 36(1).
10. Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet, 2003, 361(9351): 45-46.
11. Stamm C, Kleine HD, Westphal B, et al. CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg, 2004, 52(3): 152-158.
12. Liu C, Abedian R, Meister R, et al. Influence of perfusion and compression on the proliferation and differentiation of bone mesenchymal stromal cells seeded on polyurethane scaffolds. Biomaterials, 2012, 33(4): 1052-1064.
13. Lv L, Ren YL, Chen JC, et al. Application of CRISPRi for prokaryotic metabolic engineering involving multiple genes, a case study: Controllable P(3HB-co-4HB) biosynthesis. Metab Eng, 2015, 29: 160-168.
14. Saito Y, Doi Y. Microbial synthesis and properties of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in Comamonas acidovorans. Int J Biol Macromol, 1994, 16(2): 99-104.
15. Correia C, Serra M, Espinha N, et al. Combining hypoxia and bioreactor hydrodynamics boosts induced pluripotent stem cell differentiation towards cardiomyocytes. Stem Cell Rev, 2014, 10(6): 786-801.
16. Ng KM, Lee YK, Chan YC, et al. Exogenous expression of HIF-1 alpha promotes cardiac differentiation of embryonic stem cells. J Mol Cell Cardiol, 2010, 48(6): 1129-1137.
17. Dai Y, Xu M, Wang Y, et al. HIF-1alpha induced-VEGF over expression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol, 2007, 42(6): 1036-1044.

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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Hypoxic three-dimensional culture microenvironment promotes proliferation of bone marrow mesenchymal stem cells through HIF-1α signaling pathway

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