Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta.
Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta.
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骨髓、脂肪组织、脐带和胎盘来源的间充质干细胞促血管生成特征的异质性
DOI：
10.1186/s13287-016-0418-9
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发表时间：
2016-11-10
影响因子：
7.5
通讯作者：
Han ZC
中科院分区：
文献类型：
--
作者：
Du WJ;Chi Y;Yang ZX;Li ZJ;Cui JJ;Song BQ;Li X;Yang SG;Han ZB;Han ZC
背景间充质干细胞（mesenchymal stem cells，MSCs）在缺血动物模型和临床血管疾病中被广泛证实具有治疗血管新生的作用。由于成体组织来源的间充质干细胞的侵入性方法、有限的资源和老化问题，越来越多的围产期组织来源的间充质干细胞被分离和研究，作为细胞移植的有前途的替代间充质干细胞。然而，很少有研究比较研究了来自不同组织来源的MSC的血管生成功效。在这里，我们评估是否在原位环境会影响血管生成潜力的MSCs。MethodsWe收获的MSCs从成人骨髓（BMSCs），脂肪组织（AMSCs），围产期脐带（UMSC），胎盘绒毛膜绒毛（PMSCs），并研究其“MSC身份”通过流式细胞术和体外三系分化试验。结果UMSC和PMSC与BMSC和AMSC一样，均符合MSCs的最低标准。有趣的是，我们发现，无论其组织来源的MSC可以在体外开发类似的内皮相关功能，包括产生eNOS和摄取ac-LDL在内皮分化过程中，尽管他们的微弱表达的内皮相关基因和蛋白。此外，我们惊奇地发现，BMSC和PMSC可以在Matrigel上体外直接形成管状结构，并且与AMSC和UMSC相比，它们的条件培养基在体外对内皮细胞显示出显著的促血管生成生物活性。此外，与AMSC和UMSC相比，BMSC和PMSC中的一些血管生成基因上调。酶联免疫吸附试验进一步证实BMSCs分泌VEGF明显高于PMSCs，而PMSCs分泌HGF和PGE 2明显高于BMSCs。我们的研究表明，骨髓和胎盘绒毛来源的间充质干细胞可能是临床应用的治疗性血管生成的首选。
BackgroundMesenchymal stem cells (MSCs) have been widely proven effective for therapeutic angiogenesis in ischemia animal models as well as clinical vascular diseases. Because of the invasive method, limited resources, and aging problems of adult tissue-derived MSCs, more perinatal tissue-derived MSCs have been isolated and studied as promising substitutable MSCs for cell transplantation. However, fewer studies have comparatively studied the angiogenic efficacy of MSCs derived from different tissues sources. Here, we evaluated whether the in-situ environment would affect the angiogenic potential of MSCs.MethodsWe harvested MSCs from adult bone marrow (BMSCs), adipose tissue (AMSCs), perinatal umbilical cord (UMSCs), and placental chorionic villi (PMSCs), and studied their “MSC identity” by flow cytometry and in-vitro trilineage differentiation assay. Then we comparatively studied their endothelial differentiation capabilities and paracrine actions side by side in vitro.ResultsOur data showed that UMSCs and PMSCs fitted well with the minimum standard of MSCs as well as BMSCs and AMSCs. Interestingly, we found that MSCs regardless of their tissue origins could develop similar endothelial-relevant functions in vitro, including producing eNOS and uptaking ac-LDL during endothelial differentiation in spite of their feeble expression of endothelial-related genes and proteins. Additionally, we surprisingly found that BMSCs and PMSCs could directly form tubular structures in vitro on Matrigel and their conditioned medium showed significant proangiogenic bioactivities on endothelial cells in vitro compared with those of AMSCs and UMSCs. Besides, several angiogenic genes were upregulated in BMSCs and PMSCs in comparison with AMSCs and UMSCs. Moreover, enzyme-linked immunosorbent assay further confirmed that BMSCs secreted much more VEGF, and PMSCs secreted much more HGF and PGE2.ConclusionsOur study demonstrated the heterogeneous proangiogenic properties of MSCs derived from different tissue origins, and the in vivo isolated environment might contribute to these differences. Our study suggested that MSCs derived from bone marrow and placental chorionic villi might be preferred in clinical application for therapeutic angiogenesis.
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