PMID- 28752896 OWN - NLM STAT- MEDLINE DCOM- 20170913 LR - 20210109 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 50 IP - 5 DP - 2017 Oct TI - Metabolic reprogramming by HIF-1 activation enhances survivability of human adipose-derived stem cells in ischaemic microenvironments. LID - 10.1111/cpr.12363 [doi] LID - e12363 AB - 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 ADSCs in a simulated ischaemic microenvironment in vitro and in vivo. The underlying mechanism and angiogenesis were also studied. MATERIALS AND 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. CI - (c) 2017 John Wiley & Sons Ltd. FAU - Chen, Chang AU - Chen C AUID- ORCID: 0000-0002-6049-1193 AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Tang, Qi AU - Tang Q AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Zhang, Yan AU - Zhang Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Dai, Minjia AU - Dai M AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Jiang, Yichen AU - Jiang Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Wang, Hang AU - Wang H AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Yu, Mei AU - Yu M AUID- ORCID: 0000-0003-0306-6817 AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Jing, Wei AU - Jing W AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Tian, Weidong AU - Tian W AUID- ORCID: 0000-0003-0175-1132 AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. LA - eng PT - Journal Article DEP - 20170728 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (Amino Acids, Dicarboxylic) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - VVW38EB8YS (oxalylglycine) SB - IM MH - Adipose Tissue/*cytology MH - Amino Acids, Dicarboxylic/*pharmacology MH - Animals MH - Cell Survival/*drug effects MH - Cells, Cultured MH - Energy Metabolism/drug effects MH - Female MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*agonists/metabolism MH - Ischemia/drug therapy/metabolism MH - Mice, Nude MH - Neovascularization, Physiologic/*drug effects MH - *Stem Cell Transplantation MH - Stem Cells/cytology/*drug effects/metabolism PMC - PMC6529110 COIS- The authors declare no potential conflicts of interest. EDAT- 2017/07/29 06:00 MHDA- 2017/09/14 06:00 PMCR- 2017/07/28 CRDT- 2017/07/29 06:00 PHST- 2017/04/30 00:00 [received] PHST- 2017/06/12 00:00 [accepted] PHST- 2017/07/29 06:00 [pubmed] PHST- 2017/09/14 06:00 [medline] PHST- 2017/07/29 06:00 [entrez] PHST- 2017/07/28 00:00 [pmc-release] AID - CPR12363 [pii] AID - 10.1111/cpr.12363 [doi] PST - ppublish SO - Cell Prolif. 2017 Oct;50(5):e12363. doi: 10.1111/cpr.12363. Epub 2017 Jul 28.