Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.
Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.
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DOI：
10.1007/s10439-015-1301-z
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发表时间：
2015-10
影响因子：
3.8
通讯作者：
Truskey GA
中科院分区：
文献类型：
--
作者：
Peters EB;Liu B;Christoforou N;West JL;Truskey GA
脐带血是促血管生成治疗的一种很有前途的细胞来源。本研究检测了脐带血单个核细胞(MNC)支持内皮祖细胞(EPC)微血管形成的潜力。从20名不同捐献者的脐带血中分离出单核细胞，并根据其增殖能力和与人类血管周细胞(HVP)的形态相似性选择MNC进行进一步鉴定。使用体外试验(Matrigel™)以及还原共培养系统对单核细胞支持内皮祖细胞网络形成的能力进行筛选，该系统包括除血清中存在的那些之外不含额外的血管生成细胞因子。在不到15%的分离株中，我们鉴定了一群高增殖的MNC，通过PDGFR-β、NG2、α-SMA和ePhin-B2的表达来评估其表型与HVP相似。在Matrigel™系统中，MNC通过共定位于内皮祖细胞网络而表现出类周细胞的功能，并对内皮祖细胞总管长(p=0.95)和分支点数量(p=0.93)产生类似于HVP的影响。在还原共培养体系中，从内皮细胞总管长(p<；0.0001)和分支点数(p<；0.0001)可以看出，在共培养的第14天，单核细胞通过支持内皮祖细胞网络的形成而发挥促进血管生成的壁细胞的作用。我们的发现具有重要意义，因为我们证明了可以从脐带血中分离出壁细胞前体细胞，并开发了培养条件来支持它们在微血管组织工程应用中的使用。
Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p <0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.