Civit-Urgell Anna, Peña Esther, Bejar Maria Teresa, Moscatiello Fabrizio, Vilahur Gemma, Badimon Lina, Arderiu Gemma
Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain.
Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona (UB), Barcelona, Spain.
Diabetologia. 2025 Sep 4. doi: 10.1007/s00125-025-06533-0.
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.
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.
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.
目的/假设：本研究旨在探究碱性成纤维细胞生长因子（bFGF）能否恢复受2型糖尿病损害的脂肪来源干细胞（ASC）的增殖和迁移能力，并改善血管重塑。
将从糖尿病患者或非糖尿病患者获取的ASC与10 ng/ml bFGF一起培养9天。对ASC进行表型鉴定并对其增殖能力进行功能测试。使用miRNA芯片分析处理前后差异表达的miRNA。使用伤口愈合、Transwell迁移和共培养试验评估ASC与人血管平滑肌细胞（HVSMC）之间的相互作用。最后，在裸鼠中进行基质胶栓试验以评估ASC对新血管形成的作用。
bFGF处理显著增强了2型糖尿病患者来源的ASC（T2DM ASC）的增殖和迁移能力，并改变了与ASC增殖相关的miRNA表达。ASC促进HVSMC迁移，并且在共培养时促进管状结构形成。体内基质胶栓试验显示，bFGF处理增强了新血管形成。尽管非T2DM ASC（来自非2型糖尿病患者的ASC）和未处理的T2DM ASC均能刺激血管生成，但bFGF处理的皮下和内脏T2DM ASC促进了更大程度的新血管形成。此外，bFGF处理调节了ASC中多种血管生成相关miRNA的表达。
结论/解读：用bFGF预处理T2DM ASC可改变其miRNA谱，增强细胞增殖及其血管重塑潜能。该策略可提高T2DM ASC的治疗效用。
