Department of Cardiology, College of Medicine, Dong-A University, Busan 49201, Korea.
Department of Orthopedic Surgery, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 22711, Korea.
Int J Mol Sci. 2021 Dec 24;23(1):185. doi: 10.3390/ijms23010185.
Previously, we reported the angio-vasculogenic properties of human stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs). In this study, we investigated whether the combination of ASCs and SVF cells exhibited synergistic angiogenic properties. We conducted quantitative (q)RT-PCR, Matrigel plug, tube formation assays, and in vivo therapeutic assays using an ischemic hind limb mouse model. Immunohistochemical analysis was also conducted. qRT-PCR results revealed that FGF-2 was highly upregulated in ASCs compared with SVF, while PDGF-b and VEGF-A were highly upregulated in SVF. Conditioned medium from mixed cultures of ASCs and SVF (A+S) cells showed higher Matrigel tube formation and endothelial cell proliferation in vitro. A+S cell transplantation into ischemic mouse hind limbs strongly prevented limb loss and augmented blood perfusion compared with SVF cell transplantation. Transplanted A+S cells also showed high capillary density, cell proliferation, angiogenic cytokines, and anti-apoptotic potential in vivo compared with transplanted SVF. Our data indicate that A+S cell transplantation results in synergistic angiogenic therapeutic effects. Accordingly, A+S cell injection could be an alternative therapeutic strategy for treating ischemic diseases.
此前，我们报道了人基质血管成分 (SVF) 和脂肪组织来源的间充质干细胞 (ASC) 的血管生成特性。在这项研究中，我们研究了 ASC 和 SVF 细胞的组合是否表现出协同的血管生成特性。我们使用缺血性后肢小鼠模型进行了定量 (q)RT-PCR、Matrigel plugs、管形成测定和体内治疗测定。还进行了免疫组织化学分析。qRT-PCR 结果显示，与 SVF 相比，FGF-2 在 ASC 中高度上调，而 PDGF-b 和 VEGF-A 在 SVF 中高度上调。来自 ASC 和 SVF (A+S) 细胞混合培养的条件培养基在体外显示出更高的 Matrigel 管形成和内皮细胞增殖。与 SVF 细胞移植相比，A+S 细胞移植到缺血性小鼠后肢强烈防止了肢体丧失并增强了血液灌注。与移植的 SVF 相比，移植的 A+S 细胞在体内还显示出高毛细血管密度、细胞增殖、血管生成细胞因子和抗细胞凋亡潜能。我们的数据表明，A+S 细胞移植导致协同的血管生成治疗效果。因此，A+S 细胞注射可能是治疗缺血性疾病的一种替代治疗策略。
