Diabetes alters subsets of endothelial progenitor cells that reside in blood, bone marrow, and spleen
Diabetes alters subsets of endothelial progenitor cells that reside in blood, bone marrow, and spleen
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DOI：
10.1152/ajpcell.00380.2011
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发表时间：
2012-03-01
影响因子：
5.5
通讯作者：
Yamamoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Saito, Hidehito;Yamamoto, Yasuhiko;Yamamoto, Hiroshi
糖尿病可改变血液、骨髓和脾脏内皮祖细胞亚群。[J] .中国生物医学工程学报，2016,31(2):389 - 391。首次发表于2011年12月7日；doi: 10.1152 / ajpcell.00380.2011。来自骨髓（BM）的循环内皮祖细胞（EPCs）参与维持内皮完整性和血管稳态。糖尿病患者血管并发症的主要原因是EPC数目和功能的减少。EPCs是存在于不同分化阶段的细胞群体，其细胞表面标记谱在动员和成熟过程中发生变化。因此，普遍接受的标记组合和EPCs定量的标准化方案仍有待建立。为了确定受糖尿病影响的EPC亚群，我们采用多色流式细胞术综合分析了小鼠外周血（PB）、BM和脾脏细胞的32种表面标记组合。在链脲佐菌素诱导的糖尿病小鼠的PB中，相当于先前报道的小鼠EPCs的10个亚群的数量显著下降，这种下降被胰岛素治疗逆转。PI(-)Lin(-)c-Kit(-)Sca-1(+)Flk-1(-)CD34(-)CD31(+) EPC细胞簇在PB、BM和脾脏中数量最多，其数量是PB的61倍。在糖尿病条件下，BM和PB的细胞数量显著减少，而脾脏的细胞数量却相反地增加。胰岛素治疗逆转了BM和PB中EPC亚群的减少，逆转了脾脏中EPC亚群的增加。在db/db小鼠的一些主要细胞群中也观察到类似的趋势。据我们所知，我们是第一个报道糖尿病在小鼠血液和脾脏BM中EPCs的空间种群变化的人。糖尿病减少循环EPC供应可能归因于BM中EPC产生受损和脾脏EPC动员减少，这可能导致糖尿病患者的血管功能障碍。
Saito H, Yamamoto Y, Yamamoto H. Diabetes alters subsets of endothelial progenitor cells that reside in blood, bone marrow, and spleen. Am J Physiol Cell Physiol 302: C892-C901, 2012. First published December 7, 2011; doi: 10.1152/ajpcell.00380.2011.-Circulating endothelial progenitor cells (EPCs) derived from the bone marrow (BM) participate in maintaining endothelial integrity and vascular homeostasis. Reduced EPC number and function result in vascular complications in diabetes. EPCs are a population of cells existing in various differentiation stages, and their cell surface marker profiles change during the process of mobilization and maturation. Hence, a generally accepted marker combination and a standardized protocol for the quantification of EPCs remain to be established. To determine the EPC subsets that are affected by diabetes, we comprehensively analyzed 32 surface marker combinations of mouse peripheral blood (PB), BM, and spleen cells by multicolor flow cytometry. Ten subsets equivalent to previously reported mouse EPCs significantly declined in number in the PB of streptozotocin-induced diabetic mice, and this reduction was reversed by insulin treatment. The PI(-)Lin(-)c-Kit(-)Sca-1(+)Flk-1(-)CD34(-)CD31(+) EPC cluster, which can differentiate into mature endothelial cells in vitro, was the highest population in the PB, BM, and spleen and occurred 61 times more in the spleen than in the PB. The cell number significantly decreased in the BM as well as in the PB but paradoxically increased in the spleen under diabetic conditions. Insulin treatment reversed the decrease of EPC subsets in the BM and PB and reversed their increase in spleen. A similar tendency was observed in some of the major cell populations in db/db mice. To the best of our knowledge, we are the first to report spatial population changes in mouse EPCs by diabetes in the blood and in the BM across the spleen. Diminished circulating EPC supply by diabetes may be ascribed to impaired EPC production in the BM and to decreased EPC mobilization from the spleen, which may contribute to vascular dysfunction in diabetic conditions.