Division of Vascular Surgery, Guangdong Key Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, and The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Stem Cells Dev. 2019 Oct 15;28(20):1384-1397. doi: 10.1089/scd.2019.0115. Epub 2019 Sep 18.
Chronic critical limb ischemia (CLI) represents a clinical end stage of peripheral arterial disease. Many CLI patients are ineligible for conventional revascularization therapies; thus, it is urgent to explore an alternative strategy to rescue the ischemic limb. Recent stem cell studies have greatly developed the field of therapeutic angiogenesis, which aims to significantly improve the limb blood supply. In our study, bone marrow mesenchymal stem cells (BMMSCs) served as the control to evaluate the function of umbilical cord mesenchymal stem cells (UCMSCs) in enhancing angiogenesis. We compared gene expression between BMMSCs and UCMSCs, and a bioinformatics analysis indicated that both UCMSCs and BMMSCs could stimulate angiogenesis and angiogenesis-related factors were upregulated in UCMSCs. In vitro assays indicated that both BMMSCs and UCMSCs promoted human umbilical vein endothelial cell proliferation, migration, and tube formation, and the effects of UCMSCs were more obvious. Consistent with in vitro results, both UCMSCs and BMMSCs improved the limb blood supply in a mouse model of hind limb ischemia, in which UCMSCs promoted angiogenesis more significantly. Finally, we found that activation of ERK and PI3K-Akt pathways might be the mechanism by which UCMSCs promote angiogenesis. These results indicate that UCMSCs play an important role in therapeutic angiogenesis to improve limb blood perfusion.
慢性肢体严重缺血（CLI）代表外周动脉疾病的临床终末阶段。许多 CLI 患者不符合传统的血运重建治疗的条件；因此，迫切需要探索一种替代策略来拯救缺血肢体。最近的干细胞研究极大地推动了治疗性血管生成领域的发展，其旨在显著改善肢体血液供应。在我们的研究中，骨髓间充质干细胞（BMMSCs）作为对照，以评估脐带间充质干细胞（UCMSCs）在增强血管生成中的作用。我们比较了 BMMSCs 和 UCMSCs 之间的基因表达，生物信息学分析表明 UCMSCs 和 BMMSCs 均能刺激血管生成，UCMSCs 中血管生成相关因子上调。体外实验表明，BMMSCs 和 UCMSCs 均能促进人脐静脉内皮细胞的增殖、迁移和管腔形成，且 UCMSCs 的作用更为明显。与体外结果一致，UCMSCs 和 BMMSCs 均能改善小鼠后肢缺血模型的肢体血液供应，其中 UCMSCs 更能促进血管生成。最后，我们发现，ERK 和 PI3K-Akt 通路的激活可能是 UCMSCs 促进血管生成的机制。这些结果表明 UCMSCs 在治疗性血管生成中发挥重要作用，以改善肢体血液灌注。
