Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA,
Department of Physiology, University of Louisville, Louisville, Kentucky, USA,
J Vasc Res. 2022;59(6):343-357. doi: 10.1159/000526002. Epub 2022 Sep 8.
Adipose-derived stromal vascular fraction (SVF) has emerged as a potential regenerative therapy, but few studies utilize SVF in a setting of advanced age. Additionally, the specific cell population in SVF providing therapeutic benefit is unknown. We hypothesized that aging would alter the composition of cell populations present in SVF and its ability to promote angiogenesis following injury, a mechanism that is T cell-mediated. SVF isolated from young and old Fischer 344 rats was examined with flow cytometry for cell composition. Mesenteric windows from old rats were isolated following exteriorization-induced (EI) hypoxic injury and intravenous injection of one of four cell therapies: (1) SVF from young or (2) old donors, (3) SVF from old donors depleted of or (4) enriched for T cells. Advancing age increased the SVF T-cell population but reduced revascularization following injury. Both young and aged SVF incorporated throughout the host mesenteric microvessels, but only young SVF significantly increased vascular area following EI. This study highlights the effect of donor age on SVF angiogenic efficacy and demonstrates how the ex vivo mesenteric-window model can be used in conjunction with SVF therapy to investigate its contribution to angiogenesis.
脂肪来源的基质血管部分(SVF)已成为一种有潜力的再生治疗方法,但很少有研究在老年患者中使用 SVF。此外,SVF 中提供治疗益处的特定细胞群尚不清楚。我们假设,衰老会改变 SVF 中存在的细胞群体组成及其在损伤后促进血管生成的能力,这种机制是由 T 细胞介导的。我们使用流式细胞术检查了来自年轻和年老 Fischer 344 大鼠的 SVF 的细胞组成。在体外诱导(EI)缺氧损伤后,从老年大鼠中分离出肠系膜窗,并静脉注射四种细胞治疗方法之一:(1)来自年轻或(2)年老供体的 SVF,(3)来自年老供体耗尽或(4)富含 T 细胞的 SVF。随着年龄的增长,SVF 的 T 细胞群体增加,但损伤后再血管化减少。年轻和年老的 SVF 都遍布宿主肠系膜微血管,但只有年轻的 SVF 显著增加了 EI 后的血管面积。这项研究强调了供体年龄对 SVF 血管生成疗效的影响,并展示了如何将离体肠系膜窗模型与 SVF 治疗结合使用,以研究其对血管生成的贡献。