bFGF rescues dysfunctional properties of adipose-derived stem cells from individuals with type 2 diabetes by modulating their miRNA profile.

Abstract

AIMS/HYPOTHESIS The aim of this study was to investigate whether basic fibroblast growth factor (bFGF) can restore the proliferation and migration capacities of adipose-derived stem cells (ASCs), which are impaired by type 2 diabetes, and improve vascular remodelling. METHODS ASCs obtained from individuals with or without diabetes were cultured with 10 ng/ml bFGF for 9 days. The ASCs were phenotypically characterised and functionally tested for proliferation capacity. Differentially expressed miRNAs before and after treatment were analysed using miRNA arrays. Crosstalk between ASCs and human vascular smooth muscle cells (HVSMCs) was assessed using wound healing, transwell migration and co-culture assays. Finally, a Matrigel plug assay in nude mice was used to evaluate the contribution of ASCs to neovessel formation. RESULTS bFGF treatment significantly enhanced the proliferation and migration of ASCs from individuals with type 2 diabetes (T2DM ASCs), and altered the expression of miRNAs associated with ASC proliferation. ASCs promoted HVSMC migration and, when co-cultured, facilitated tube-like structure formation. In vivo Matrigel plug assays revealed that bFGF treatment enhanced neovessel formation. Although both non-T2DM ASCs (ASCs from individuals without type 2 diabetes) and untreated T2DM ASCs stimulated angiogenesis, bFGF-treated subcutaneous and visceral T2DM ASCs promoted even greater neovessel formation. Additionally, bFGF treatment modulated the expression of multiple angiogenesis-related miRNAs in ASCs. CONCLUSIONS/INTERPRETATION Preconditioning T2DM ASCs with bFGF alters their miRNA profile, enhancing cell proliferation and their vascular remodelling potential. This strategy could improve the therapeutic utility of T2DM ASCs.