Research Paper|Volume 12, Issue 8|pp 6947—6965

Diabetes-induced glucolipotoxicity impairs wound healing ability of adipose-derived stem cells-through the miR-1248/CITED2/HIF-1α pathway

Shune Xiao¹, Dan Zhang², Zhiyuan Liu¹, Wenhu Jin¹, Guangtao Huang¹, Zairong Wei¹, Dali Wang¹, Chengliang Deng¹

¹Department of Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
²Department of Orthodontics, Stomatological Hospital of Zunyi Medical University, Zunyi, Guizhou, China

* Co-first authors

Received: July 30, 2019Accepted: March 29, 2020Published: April 15, 2020

Copyright © 2020 Xiao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Despite being an attractive cell type for mesenchymal stem cell (MSC) transplantation therapy for wound healing, human adipose-derived stem cells (hADSCs) from diabetes mellitus (DM) patients result in remarkable retention of stem cell activity due to diabetes-induced glucolipotoxicity. We explored the effect of diabetes and medium containing AGEs on the cell activity, phenotype, multipotency, angiogenic potential, and the therapeutic effect of hADSCs. Then, miRNA-1248 was selected by miRNA microarray analysis to further study the core molecular pathways that regulate the wound healing ability of hADSCs. hADSCs isolated from DM patients or cultured in medium containing AGEs in vitro exhibited decreased effectiveness in stem cell therapy. The expression of miRNA-1248 was decreased in the hADSCs of DM patients and hence failed to positively regulate stem cell activity, differentiation functions, and angiogenesis promotion effect. This concomitantly increased the expression of CITED2, an inhibitor of HIF-1α, thus influencing growth factors that promote angiogenesis, cellular proliferation, and wound healing. Overall, our data demonstrated that the glucolipotoxicity-impaired wound healing ability of hADSCs might occur through the miR-1248/CITED2/HIF-1α pathway. MiRNA-1248 may have potential to be used as a novel therapeutic target for wound healing in DM patients or restoring the wound healing ability of diabetic hADSCs.