Comparative studies on the effect of pig adipose-derived stem cells (pASCs) preconditioned with hypoxia or normoxia on skin wound healing in mice

Adipose-derived stem cells (ASCs) from human and animal fat have emerged as therapeutic alternatives for damaged tissues. Pre-conditioning of ASCs with hypoxia results in their functional enhancement, which might facilitate the process of healing. However, there is still a critical need for large-sc...

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Published in:Experimental cell research 2022-09, Vol.418 (1), p.113263-113263, Article 113263
Main Authors: Wiśniewska, Joanna, Słyszewska, Magda, Kopcewicz, Marta, Walendzik, Katarzyna, Machcińska, Sylwia, Stałanowska, Karolina, Gawrońska-Kozak, Barbara
Format: Article
Language:English
Subjects:
Adipose-derived stem cells
Cell-based therapy
Hypoxia preconditioning
Livestock animals
Wound healing
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Summary:Adipose-derived stem cells (ASCs) from human and animal fat have emerged as therapeutic alternatives for damaged tissues. Pre-conditioning of ASCs with hypoxia results in their functional enhancement, which might facilitate the process of healing. However, there is still a critical need for large-scale preclinical studies to reinforce the translation of these findings into clinical practice for humans and in veterinary medicine. Here, we adapted a full-thickness excisional skin wound mouse model to evaluate and compare the effect of pig adipose-derived stem cells (pASCs) cultured under normoxia (pASCs-Nor) or hypoxia (pASCs-Hyp) on the healing process. We show that pASCs-Hyp accelerated re-epithelialization, increased hyaluronic acid (HA) content, and decreased scar elevation index (SEI) during the late stage of healing (day 21). Transplantation of pASCs-Hyp also promoted expression of angiogenic marker VegfA and decreased levels of pro-scarring Tgfβ1. Mice tolerated xenotransplantation of the pASCs with no impact on macrophage (CD68 -positive cell) content. However, wounds treated with pASCs-Hyp exhibited decreased elasticity at the early stage of healing and increased expression of Wnt signaling members including Wnt10a, Wnt11, and β-catenin, which are associated with scar-forming wound repair. In conclusion, pASCs treatment may provide a critical step toward the evaluation of pASCs as therapeutically relevant cells in the context of wound healing. •Pre-conditioning of pASCs with hypoxia (pASC-Hyp) impacts their effectiveness in skin wound healing.•pASCs xenotransplantation has no impact on macrophage content.•pASCs-Hyp accelerate re-epithelialization and decrease scar elevation index.•pASCs-Hyp promote expression of angiogenic marker Vegfa and decrease pro-scarring Tgfβ1.•pASCs-Hyp increase expression of Wnt10a, Wnt11, and β-catenin associated with scar-forming wound repair.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2022.113263