Cell Transplantation (Nov 2023)

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

  • Kai Zhang,
  • Dan Jin,
  • Xin Zhao,
  • Bin Lu,
  • Weiwei Guo,
  • Rui Ren,
  • Simo Wu,
  • Junrui Zhang,
  • Yunpeng Li

DOI
https://doi.org/10.1177/09636897231210750
Journal volume & issue
Vol. 32

Abstract

Read online

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.