Metabolic reprogramming by HIF-1 activation enhances survivability of human adipose-derived stem cells in ischaemic microenvironments

通过 HIF-1 激活进行代谢重编程可增强人类脂肪干细胞在缺血微环境中的生存能力

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作者:Chang Chen, Qi Tang, Yan Zhang, Minjia Dai, Yichen Jiang, Hang Wang, Mei Yu, Wei Jing, Weidong Tian

Conclusions

The promotion of HIF-1 level in ADSCs induced by DMOG preconditioning suggests a potential strategy for improving the outcome of cell therapy due to increased survival and angiogenic ability.

Methods

Survivability of ADSCs was determined in a simulated ischaemic model in vitro and a nude mouse model in vivo. Cell metabolism and angiogenesis were investigated by tube formation assay, flow cytometry, fluorescence staining and real-time polymerase chain reaction (RT-PCR) after DMOG treatment.

Results

The results of the experimental groups showed significant enhancement of ADSC survivability in a simulated ischaemic microenvironment in vitro and transplanted model in vivo. Study of the underlying mechanisms suggested that the improved cell survival was regulated by HIF-1-induced metabolic reprogramming including decreased reactive oxygen species, increased intracellular pH, enhanced glucose uptake and increased glycogen synthesis. Tube formation assay revealed higher angiogenic ability in the DMOG-treated group than that in control group. Conclusions: The promotion of HIF-1 level in ADSCs induced by DMOG preconditioning suggests a potential strategy for improving the outcome of cell therapy due to increased survival and angiogenic ability.

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