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缺氧在脐带间充质干细胞的活力和内皮分化潜能以及血管内皮生长因子干扰中的作用

Role of hypoxia in viability and endothelial differentiation potential of UC-MSCs and VEGF interference.

作者信息

Li Peng, Zhou Changyong, Yin Lei, Meng Xianqin, Zhang Lina

机构信息

Department of Emergency Room, Qingdao University, Qingdao Shandong, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Apr;38(4):329-40. doi: 10.3969/j.issn.1672-7347.2013.04.001.

DOI:10.3969/j.issn.1672-7347.2013.04.001
PMID:23645232
Abstract

OBJECTIVE

To investigate the effect of hypoxia on cell viability and the endothelial differentiation potential in human umbilical cord derived mesenchymal stem cells (UC-MSCs), and to assess the in vitro protective role of VEGF under low oxygen tension.

METHODS

MSCs were isolated from human umbilical cords and cultured in vitro. The morphological and phenotypic characterizations of human UC-MSCs were analyzed. The hypoxia induction was performed with or without the presence of 50 ng/mL of VEGF for different lengths of time. The cell proliferation, apoptosis, and reactive oxygen species (ROS) generation were assessed. Meanwhile, the endothelial differentiation potential of the UC-MSCs was measured.

RESULTS

An increased apoptosis and ROS generation but reduced proliferation rate were observed at early stages (6, 12 h) after transferring the UC-MSCs from the atmospheric condition to the hypoxia condition. However, the UC-MSCs presented equal proliferation and apoptosis levels under hypoxic condition as compared with those under the atmospheric condition at the later stages (24, 72 h). A high concentration of exogenous VEGF (50 ng/mL) attenuated the increased apoptosis and inhibited the proliferation of UC-MSCs, induced by a short-term hypoxia treatment. After 14 days of exogenous VEGF induction under the hypoxia condition, the UC-MSCs acquired an early endothelial phenotype consisting of a mature endothelial molecule and some endothelial functions.

CONCLUSION

UC-MSCs progressively adapt to hypoxia in a step-by-step manner and maintain differentiation potential under hypoxia condition. VEGF can protect the UC-MSCs from cell damage and induce a differentiation of UC-MSCs toward endothelial lineage under hypoxic conditions.

摘要

目的

研究缺氧对人脐带间充质干细胞(UC-MSCs)细胞活力及内皮分化潜能的影响,并评估低氧张力下血管内皮生长因子(VEGF)的体外保护作用。

方法

从人脐带中分离出间充质干细胞并进行体外培养。分析人UC-MSCs的形态和表型特征。在有或无50 ng/mL VEGF存在的情况下,进行不同时长的缺氧诱导。评估细胞增殖、凋亡及活性氧(ROS)生成情况。同时,检测UC-MSCs的内皮分化潜能。

结果

将UC-MSCs从常氧条件转移至缺氧条件后的早期阶段(6、12小时),观察到细胞凋亡增加、ROS生成增加但增殖率降低。然而,在后期阶段(24、72小时),UC-MSCs在缺氧条件下的增殖和凋亡水平与常氧条件下相当。高浓度外源性VEGF(50 ng/mL)可减轻短期缺氧处理诱导的UC-MSCs凋亡增加并抑制其增殖。在缺氧条件下外源性VEGF诱导14天后,UC-MSCs获得了由成熟内皮分子和一些内皮功能组成的早期内皮表型。

结论

UC-MSCs以逐步的方式逐渐适应缺氧,并在缺氧条件下维持分化潜能。VEGF可保护UC-MSCs免受细胞损伤,并在缺氧条件下诱导UC-MSCs向内皮谱系分化。

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