1. Academic Validation
  2. HIF-1α-Induced Mitophagy Regulates the Regenerative Outcomes of Stem Cells in Fat Transplantation

HIF-1α-Induced Mitophagy Regulates the Regenerative Outcomes of Stem Cells in Fat Transplantation

  • Cell Transplant. 2023 Jan-Dec:32:9636897231210750. doi: 10.1177/09636897231210750.
Kai Zhang 1 Dan Jin 1 Xin Zhao 2 Bin Lu 1 Weiwei Guo 1 Rui Ren 1 Simo Wu 1 Junrui Zhang 1 Yunpeng Li 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, P.R. China.
  • 2 Xijing 986 Hospital Department, Fourth Military Medical University, Xi'an, P.R. China.
Abstract

Hypoxia is a crucial factor with type diversity that plays an important role in stem cell transplantation. However, the effects of hypoxia on adipose-derived stem cells (ADSCs) are largely unclear in the autologous fat transplantation (AFT) model, which shows a special type of "acute-progressively resolving hypoxia." Here, an AFT model in nude mice and a hypoxic culture model for ADSCs were combined to explore the link between hypoxia-inducible factor-1 α subunit (HIF-1α) and Mitophagy under hypoxic conditions. The results showed that the activity of ADSCs in the first 7 days after grafting was the key stage for volume retention, and the expression of HIF-1α, LIGHT chain 3 beta (LC3B), and Beclin1 in ADSCs increased during this period. We also found that hypoxia for longer than 48 h damaged the differentiation and mitochondrial respiration of ADSCs in vitro, but hypoxia signals also activate HIF-1α to initiate Mitophagy and maintain the activities of ADSCs. Pre-enhancing Mitophagy by rapamycin effectively improves mitochondrial respiration in ADSCs after grafting and ultimately improves AFT outcomes.

Keywords

HIF-1α; adipose-derived stem cells; autologous fat transplantation; cell transplantation; hypoxia; mitophagy.

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