Bcl-2 Overexpression and Hypoxia Synergistically Enhance Angiogenic Properties of Dental Pulp Stem Cells

被引：18
作者：
Dissanayaka, Waruna L. [1 ]
Han, Yuanyuan [1 ]
Zhang, Lili [1 ]
Zou, Ting [2 ]
Zhang, Chengfei [2 ]
机构：
[1] Univ Hong Kong, Fac Dent, Appl Oral Sci & Community Dent Care, Hong Kong, Peoples R China
[2] Univ Hong Kong, Fac Dent, Restorat Dent Sci, Hong Kong, Peoples R China
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 17期
关键词：
Bcl-2; gene modification; angiogenesis; post-implantation cell survival; vascularization; tissue regeneration; dental pulp stem cells; ENDOTHELIAL GROWTH-FACTOR; KAPPA-B ACTIVITY; INDUCED APOPTOSIS; UP-REGULATION; EXPRESSION; CANCER; VASCULARIZATION; STABILIZATION; TRANSCRIPTION; REGENERATION;
D O I：
10.3390/ijms21176159
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Post-implantation cell survival and angio-/vasculogenesis are critical for the success of cell-based regenerative strategies. The current study aimed to overexpress B-cell lymphoma 2 (Bcl-2) gene in dental pulp stem cells (DPSCs) and examine the anti-apoptotic and angio-/vasculogenic effects both in-vitro and in-vivo. DPSCs were transduced with Bcl-2-green fluorescent protein (GFP) lentiviral particles and examined for cell proliferation and apoptosis. The cells were cultured under normoxic or hypoxic (0.5 mM CoCl2) conditions and examined for the expression of angiogenic factors and effects on endothelial cell proliferation, migration and vessel morphogenesis. Cells with or without hypoxic preconditioning were used in in-vivo Matrigel plug assay to study the post-implantation cell survival and angio-/vasculogenesis. Bcl-2-overexpressing-DPSCs showed significantly lower apoptosis than that of null-GFP-DPSCs under serum-free conditions. Under hypoxia, Bcl-2-overexpressing-DPSCs expressed significantly higher levels of vascular endothelial growth factor compared to that under normoxia and null-GFP-DPSCs. Consequently, Bcl-2-overexpressing-DPSCs significantly enhanced endothelial cell proliferation, migration and vascular tube formation on Matrigel. Immunohistological assessment of in-vivo transplanted Matrigel plugs showed significantly higher cell survival and vasculature in hypoxic preconditioned Bcl-2-overexpressing-DPSC group compared to null-GFP-DPSC group. In conclusion, Bcl-2 overexpression and hypoxic-preconditioning could be synergistically used to enhance post-implantation cell survival and angio-/vasculogenic properties of DPSCs.
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页码：1 / 19
页数：19
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