Hipoxia modulates the secretion of growth factors of human umbilical cord-derived mesenchymal stem cells

缺氧调节人脐带间充质干细胞生长因子的分泌

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作者:Arfianti Arfianti, Ulfah, Leopold S Hutabarat, G Agnes Ivana, Anisa D Budiarti, Nabilla S Sahara, Nicko P K Saputra

Background

Mesenchymal stem cell (MSC) has great potential as therapies due its ability to regenerate tissue damage and promote tissue homeostasis. Preconditioning of MSC in low oxygen concentration has been shown to affect the therapeutic potential of these cells. This study aimed to compare the characteristic and secretion of trophic factors of MSCs cultured under hypoxia and normoxia.

Conclusions

Hypoxia decreased the metabolic activity of MSCs associated with the modulation of HGF and VEGF secretions. It is suggested that hypoxia may also affect the therapeutic capacity of MSC cells.

Methods

MSCs were isolated from Wharton's jelly of human umbilical cord (UC) tissue by explant method and characterized by flow cytometry. Following 24 h of CoCl2-induced hypoxic culture, the viability and metabolic activity of MSC were analyzed by trypan blue exclusion test and methyl thiazolyl tetrazolium (MTT) assay, respectively. The secretion of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) was assessed in conditioned medium using enzyme-linked immunosorbent assay (ELISA) method.

Results

Flow cytometry analysis showed >99% of the population of MSCs cells were positive for CD73 and CD90 and > 62% were positive for CD105. While the cell viability of MSC was not affected by hypoxic cultured condition, the metabolic activity rate of these cells was decreased under hypoxic conditioning. In line with reduced metabolic activity, hypoxic human UC-derived MSC produced less HGF than normoxic counterpart. Compared to normoxic MSC, hypoxic preconditioned MSC secreted higher level of VEGF in the conditioned medium (p < 0.05). Conclusions: Hypoxia decreased the metabolic activity of MSCs associated with the modulation of HGF and VEGF secretions. It is suggested that hypoxia may also affect the therapeutic capacity of MSC cells.

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