Adipose-derived mesenchymal stem cell-loaded β-chitin nanofiber hydrogel activates the AldoA/HIF-1α pathway to promote diabetic wound healing

Ying Liu; Ruihang Ma; Du Juan; Zhixin Yuan; Jiuhui Sun; Mengjun Wang; Yuxuan Li; Yongli Bao; Hongxu Jin

Adipose-derived mesenchymal stem cell-loaded β-chitin nanofiber hydrogel activates the AldoA/HIF-1α pathway to promote diabetic wound healing

Am J Stem Cells. 2023 Feb 25;12(1):1-11. eCollection 2023.

Authors

Ying Liu¹, Ruihang Ma¹, Du Juan², Zhixin Yuan³, Jiuhui Sun¹, Mengjun Wang¹, Yuxuan Li⁴, Yongli Bao⁵, Hongxu Jin¹

Affiliations

¹ Emergency Medicine Department of General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Wound and Trauma PLA Shenyang 110016, Liaoning, China.
² Diabetic Foot Diagnosis and Treatment Center, Jilin Province People Hospital Changchun 130021, Jilin, China.
³ Department of Emergency Surgery, Jilin Province People Hospital Changchun 130021, Jilin, China.
⁴ China Medical University Shenyang 110002, Liaoning, China.
⁵ National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University Changchun 130117, Jilin, China.

PMID: 36937028
PMCID: PMC10018006

Abstract

Objectives: To identify the effect of adipose-derived mesenchymal stem cell-loaded β-chitin nanofiber (ADSC-loaded β-ChNF) hydrogel on diabetic wound healing and clarify its mechanism of action.

Methods: We prepared the ADSC-loaded β-ChNF hydrogel to repair wounds of db/db diabetic mice. Wound healing rate, histopathology, enzyme-linked immunosorbent assay, and western blot were used to confirm its role and mechanism in promoting diabetic wound healing.

Results: The ADSC-loaded β-ChNF hydrogel accelerated wound healing in db/db diabetic mice, as indicated by increased cell proliferation, epithelization, and tissue granulation in the skin. Moreover, expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), matrix metalloproteinase 9 (MMP9), and TIMP metallopeptidase inhibitor 1 (TIMP1) were upregulated. These results demonstrate the beneficial effects of this ADSC-loaded β-ChNF hydrogel on diabetic wound healing. Furthermore, we show that the ADSC-loaded β-ChNF hydrogel activated aldolase A (AldoA)/hypoxia-inducible factor 1α (HIF-1α) signaling. An inhibitor of HIF-1α markedly decreased the promotive effects of the ADSC-loaded β-ChNF hydrogel on wound healing and reduced expression of VEGF, VEGFR, MMP9, and TIMP1.

Conclusions: Our findings suggest that the ADSC-loaded β-ChNF hydrogel activated the HIF-1α/MMP9 axis through AldoA feedback to promote diabetic wound healing.

Keywords: Adipose-derived mesenchymal stem cell; AldoA; HIF-1α; MMP9; β-chitin nanofiber hydrogel.