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.