PMID- 33358677
OWN - NLM
STAT- MEDLINE
DCOM- 20210825
LR  - 20210825
IS  - 1878-0539 (Electronic)
IS  - 1748-6815 (Linking)
VI  - 74
IP  - 8
DP  - 2021 Aug
TI  - HIF-1alpha inhibits mitochondria-mediated apoptosis and improves the survival of 
      human adipose-derived stem cells in ischemic microenvironments.
PG  - 1908-1918
LID - S1748-6815(20)30660-4 [pii]
LID - 10.1016/j.bjps.2020.11.041 [doi]
AB  - BACKGROUND: Human adipose mesenchymal stem cells (hADSCs) show poor survival 
      after transplantation, limiting their clinical application. Tissue regeneration 
      resulting from stem cell treatment may be caused by attenuation of 
      hypoxia-inducible factor-1alpha (HIF-1alpha). In this study, we constructed hADSCs stably 
      expressing HIF-1alpha and investigated the potential effects of HIF-1alpha expression in 
      the ischemic microenvironment on mitochondrial apoptosis and survival of hADSCs, 
      and studied the mechanisms involved. METHOD: Apoptosis was induced by an ischemic 
      microenvironment in vitro. ADSCs with stable HIF-1alpha expression were established. 
      Cell survival and apoptosis were observed by CCK-8 assay, western blotting, flow 
      cytometry, and fluorescence staining. ADSCs were subcutaneously transplanted into 
      nude mice in the location where a hypoxia ischemic microenvironment was simulated 
      in vivo. After 1, 3, and 7 d, mitochondrial apoptotic proteins were evaluated by 
      immunohistochemistry and immunofluorescence staining. RESULTS: Exogenous HIF-1alpha 
      downregulated mitochondrial reactive oxygen species, cytochrome c, caspase-9, and 
      caspase-3, but inhibited mitochondrial membrane potential depolarization and 
      increased the Bcl-2/bax ratio. HIF-1alpha prevented apoptosis and promoted vascular 
      endothelial growth factor (VEGF) secretion as demonstrated by enzyme-linked 
      immunosorbent assay (ELISA), terminal deoxyribonucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL) staining, and flow cytometry analysis. HIF-1alpha 
      enhanced the survival of transplanted ADSCs in nude mice. CONCLUSION: We have 
      shown that through inhibition of the mitochondria-mediated apoptotic pathway and 
      promotion of VEGF secretion in hADSCs in an ischemic microenvironment, HIF-1alpha may 
      potentially be applied in clinical therapy and as an alternative strategy for 
      improving hADSC therapy.
CI  - Copyright (c) 2020 British Association of Plastic, Reconstructive and Aesthetic 
      Surgeons. Published by Elsevier Ltd. All rights reserved.
FAU - Wang, Jie
AU  - Wang J
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Zhou, Yongting
AU  - Zhou Y
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Pang, Hao
AU  - Pang H
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Oganezov, Giorgi
AU  - Oganezov G
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Lv, Tianqi
AU  - Lv T
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Li, Jiaxu
AU  - Li J
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China.
FAU - Xu, Jiayi
AU  - Xu J
AD  - Department of Medicine, Jiamusi University, Jiamusi 154007, People's Republic of 
      China.
FAU - Xiao, Zhibo
AU  - Xiao Z
AD  - Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of 
      Harbin Medical University, Harbin 150081, People's Republic of China. Electronic 
      address: xiaozhibodoctor@126.com.
FAU - Dong, Xiaoqun
AU  - Dong X
AD  - Department of Medicine, Warren Alpert Medical School of Brown University, Rhode 
      Island, USA.
LA  - eng
PT  - Journal Article
DEP - 20201211
PL  - Netherlands
TA  - J Plast Reconstr Aesthet Surg
JT  - Journal of plastic, reconstructive & aesthetic surgery : JPRAS
JID - 101264239
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Adipose Tissue/*cytology
MH  - Adult
MH  - Apoptosis/*physiology
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - In Vitro Techniques
MH  - Ischemia/*physiopathology
MH  - Mitochondria/*metabolism
MH  - *Stem Cell Transplantation
OTO - NOTNLM
OT  - Apoptosis
OT  - HIF-1alpha
OT  - Ischemic microenvironment
OT  - Mitochondria
OT  - hADSC
COIS- Declaration of competing Interest The authors declare that they have no competing 
      interests
EDAT- 2020/12/29 06:00
MHDA- 2021/08/26 06:00
CRDT- 2020/12/28 10:39
PHST- 2020/04/01 00:00 [received]
PHST- 2020/11/15 00:00 [revised]
PHST- 2020/11/22 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/08/26 06:00 [medline]
PHST- 2020/12/28 10:39 [entrez]
AID - S1748-6815(20)30660-4 [pii]
AID - 10.1016/j.bjps.2020.11.041 [doi]
PST - ppublish
SO  - J Plast Reconstr Aesthet Surg. 2021 Aug;74(8):1908-1918. doi: 
      10.1016/j.bjps.2020.11.041. Epub 2020 Dec 11.