Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Stem Cells. 2019 Jan;37(1):77-88. doi: 10.1002/stem.2920. Epub 2018 Oct 8.
Mesenchymal stromal/stem cells (MSCs) have been developed as a promising source for cell-based therapies of ischemic disease. However, there are some hurdles in their clinical application such as poor cell engraftment and inconsistent stem cell potency. In this study, we sought to find biomarkers for predicting potency of MSCs for proangiogenic therapy to improve their beneficial effects. Large variations were observed in proangiogenic factor secretion profiles of conditioned media derived from nine different donor-derived Wharton's jelly (WJ)-derived MSCs and 8 factors among 55 angiogenesis-related factors were secreted at considerable levels. Two distinct WJ-MSCs that had the lowest or the highest secretion of these eight factors showed corresponding proangiogenic activities in in vitro angiogenesis assays. When four additional different donor-derived WJ-MSCs were further examined, proangiogenic activities in migration and tube formation of endothelial cells and in in vivo Matrigel plug assay were highly consistent with secretion levels of four major factors (angiogenin, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor). Such correlation was also observed in vascular regenerative effect in a mouse hind limb ischemia model. Blocking of these four factors by neutralizing antibodies or knockdown of them by siRNA treatment resulted in significant inhibition of proangiogenic activities of not only WJ-MSCs, but also bone marrow-derived MSCs. These results suggest that these four factors may represent efficient biomarkers for predicting vascular regenerative efficacy of MSCs. Stem Cells 2019;37:77-88.
间充质基质/干细胞（MSCs）已被开发为缺血性疾病细胞治疗的有前途的来源。然而，在其临床应用中存在一些障碍，例如细胞植入不良和干细胞效力不一致。在这项研究中，我们试图寻找预测 MSCs 用于促血管生成治疗效力的生物标志物，以提高其有益效果。从 9 个不同供体来源的 Wharton 胶（WJ）衍生 MSC 中获得的条件培养基的促血管生成因子分泌谱存在很大差异，55 种血管生成相关因子中有 8 种因子以相当高的水平分泌。两种具有最低或最高这八种因子分泌的不同 WJ-MSC 在体外血管生成测定中显示出相应的促血管生成活性。当进一步检查另外 4 个不同供体来源的 WJ-MSC 时，内皮细胞迁移和管形成以及体内 Matrigel 塞植入测定中的促血管生成活性与四种主要因子（血管生成素、白细胞介素 8、单核细胞趋化蛋白 1 和血管内皮生长因子）的分泌水平高度一致。在小鼠后肢缺血模型中的血管再生效应中也观察到了这种相关性。用中和抗体阻断这四种因子或用 siRNA 处理敲低它们，不仅会显著抑制 WJ-MSC 的促血管生成活性，还会抑制骨髓来源的 MSC 的促血管生成活性。这些结果表明，这四种因子可能代表预测 MSC 血管再生功效的有效生物标志物。干细胞 2019；37:77-88。
