ID2019 Functional analysis of human type 2 diabetic adipose tissue-derived mesenchymal stem cells
DOI:
https://doi.org/10.15419/bmrat.v4iS.262Keywords:
diabetes, EGR-1, microvesicles, stem cellsAbstract
Background: Stem cell therapy has recently shown promise in the prevention of diabetic complications due to its regenerative potential. The possible applications of human diabetic adipose tissue-derived mesenchymal stem cells (dAT-MSCs) in cell therapy are limited because their characteristics are still not fully understood. Aims: This study aimed to characterize dAT-MSCs in vitro and to investigate the potential application of dAT-MSCs in wound healing. Materials and Methods: dAT-MSCs were characterized under normoxic and hypoxic conditions in vitro and evaluated wound healing capacity in the ischemic flap mouse model. Results: Early growth response factor-1 (EGR-1) and its target genes were highly expressed in dAT-MSCs in comparison to nAT-MSCs, resulting in increasing of genes and protein associated with cell adhesion, insulin resistance, and impaired wound healing. Interestingly, under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) can bind to the EGR-1 promoter in dAT-MSCs, but not in nAT-MSCs. The effects of EGR-1 were inhibited by shEGR-1 and PD98059. Mice injected with shEGR-1- dAT-MSCs were improved their wound healing capacity. Furthermore, we found that human nAT-MSC-derived microvesicles (nMVs) could improve dAT-MSC function by altering miRNA and mRNA expressions, which enhanced their migration ability in vitro and wound healing capacity in the ischemic flap mouse model. Conclusion: Our study suggests that dAT-MSCs may contribute to delay wound healing. Interrupting the expression of EGR-1 in dAT-MSCs or transfecting nMVs to dAT-MSCs may be a useful treatment for chronic wounds in diabetic patients.
Downloads
Published
Issue
Section
License
Copyright The Author(s) 2017. This article is published with open access by BioMedPress. This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.