Open AccessMetabolic reprogramming by HIF ‐1 activation enhances survivability of human adipose‐derived stem cells in ischaemic microenvironments
Author(s) -
Chen Chang,
Tang Qi,
Zhang Yan,
Dai Minjia,
Jiang Yichen,
Wang Hang,
Yu Mei,
Jing Wei,
Tian Weidong
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12363
Subject(s) - adipose tissue , stem cell , angiogenesis , in vivo , mesenchymal stem cell , microbiology and biotechnology , cell therapy , biology , flow cytometry , chemistry , andrology , immunology , cancer research , biochemistry , medicine
Objectives Poor cell survival severely limits the beneficial effect of adipose‐derived stem cell ( ADSC )‐based therapy for disease treatment and tissue regeneration, which might be caused by the attenuated level of hypoxia‐inducible factor‐1 ( HIF ‐1) in these cells after having been cultured in 21% ambient oxygen in vitro for weeks. In this study, we explored the role of pre‐incubation in dimethyloxalylglycine ( DMOG , HIF ‐1 activator) in the survivability of human ADSC s in a simulated ischaemic microenvironment in vitro and in vivo. The underlying mechanism and angiogenesis were also studied. Materials and methods Survivability of ADSC s 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 ADSC s induced by DMOG preconditioning suggests a potential strategy for improving the outcome of cell therapy due to increased survival and angiogenic ability.