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Umbilical artery tissue contains p75 neurotrophin receptor-positive pericyte-like cells that possess neurosphere formation capacity and neurogenic differentiation potential
Regenerative Therapy ( IF 3.4 ) Pub Date : 2020-12-24 , DOI: 10.1016/j.reth.2020.12.002
Rina Fujii-Tezuka 1 , Mika Ishige-Wada 1 , Narihito Nagoshi 2 , Hideyuki Okano 3 , Hideo Mugishima 1, 4 , Shori Takahashi 1, 5 , Ichiro Morioka 1 , Taro Matsumoto 6
Affiliation  

Introduction

The p75 neurotrophin receptor (p75NTR) is known as an efficient marker for the prospective isolation of mesenchymal stem cells (MSCs) and neural crest-derived stem cells (NCSCs). To date, there is quite limited information concerning p75NTR-expressing cells in umbilical cord (UC), although UC is known as a rich source of MSCs. We show for the first time the localization, phenotype, and functional properties of p75NTR+ cells in UC.

Methods

Human UC tissue sections were subjected to immunohistochemistry for MSC markers including p75NTR. Enzymatically isolated umbilical artery (UA) cells containing p75NTR+ cells were assessed for immunophenotype, clonogenic capacity, and differentiation potential. To identify the presence of neural crest-derived cells in the UA, P0-Cre/Floxed-EGFP reporter mouse embryos were used, and immunohistochemical analysis of UC tissue was performed.

Results

Immunohistochemical analysis revealed that p75NTR+ cells were specifically localized to the subendothelial area of the UA and umbilical vein. The p75NTR+ cells co-expressed PDGFRβ, CD90, CD146, and NG2, phenotypic markers of MSCs and pericytes. Isolated UA cells possessed the potential to form neurospheres that further differentiated into neuronal and glial cell lineages. Genetic lineage tracing analysis showed that EGFP+ neural crest-derived cells were detected in the subendothelial area of UA with p75NTR immunoreactivity.

Conclusions

These results show that UA tissue harbors p75NTR+ pericyte-like cells in the subendothelial area that have the capacity to form neurospheres and the potential for neurogenic differentiation. The lineage tracing data suggests the p75NTR+ cells are putatively derived from the neural crest.



中文翻译:


脐动脉组织含有 p75 神经营养蛋白受体阳性周细胞样细胞,具有神经球形成能力和神经源性分化潜力


 介绍


p75 神经营养蛋白受体 (p75NTR) 被认为是前瞻性分离间充质干细胞 (MSC) 和神经嵴衍生干细胞 (NCSC) 的有效标记。迄今为止,尽管脐带 (UC) 被认为是 MSC 的丰富来源,但有关脐带 (UC) 中表达 p75NTR 的细胞的信息相当有限。我们首次展示了 UC 中 p75NTR +细胞的定位、表型和功能特性。

 方法


对人 UC 组织切片进行免疫组织化学检测 MSC 标记物,包括 p75NTR。评估酶法分离的含有 p75NTR +细胞的脐动脉 (UA) 细胞的免疫表型、克隆形成能力和分化潜力。为了鉴定 UA 中神经嵴衍生细胞的存在,使用 P0-Cre/Floxed-EGFP 报告小鼠胚胎,并对 UC 组织进行免疫组织化学分析。

 结果


免疫组织化学分析显示,p75NTR +细胞特异性定位于 UA 和脐静脉的内皮下区域。 p75NTR +细胞共表达 PDGFRβ、CD90、CD146 和 NG2(MSC 和周细胞的表型标记物)。分离的UA细胞具有形成神经球的潜力,神经球进一步分化为神经元和神经胶质细胞谱系。遗传谱系追踪分析显示,在UA内皮下区域检测到EGFP +神经嵴衍生细胞,具有p75NTR免疫反应性。

 结论


这些结果表明,UA 组织在内皮下区域含有 p75NTR +周细胞样细胞,这些细胞具有形成神经球的能力和神经源性分化的潜力。谱系追踪数据表明 p75NTR +细胞可能源自神经嵴。

更新日期:2020-12-25
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