Fujii-Tezuka Rina, Ishige-Wada Mika, Nagoshi Narihito, Okano Hideyuki, Mugishima Hideo, Takahashi Shori, Morioka Ichiro, Matsumoto Taro
Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Regen Ther. 2020 Dec 24;16:1-11. doi: 10.1016/j.reth.2020.12.002. eCollection 2021 Mar.
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.
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.
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.
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.
p75神经营养因子受体（p75NTR）是用于前瞻性分离间充质干细胞（MSC）和神经嵴衍生干细胞（NCSC）的有效标志物。尽管脐带（UC）是已知的MSC丰富来源，但迄今为止，关于脐带中表达p75NTR的细胞的信息相当有限。我们首次展示了脐带中p75NTR细胞的定位、表型和功能特性。
对人脐带组织切片进行免疫组织化学检测，以检测包括p75NTR在内的MSC标志物。对含有p75NTR细胞的酶解分离的脐动脉（UA）细胞进行免疫表型、克隆形成能力和分化潜能评估。为了鉴定脐动脉中神经嵴衍生细胞的存在，使用了P0-Cre/Floxed-EGFP报告基因小鼠胚胎，并对脐带组织进行了免疫组织化学分析。
免疫组织化学分析显示，p75NTR细胞特异性定位于脐动脉和脐静脉的内皮下区域。p75NTR细胞共表达PDGFRβ、CD90、CD146和NG2，这些是MSC和周细胞的表型标志物。分离的脐动脉细胞具有形成神经球的潜力，这些神经球可进一步分化为神经元和神经胶质细胞谱系。遗传谱系追踪分析表明，在具有p75NTR免疫反应性的脐动脉内皮下区域检测到了EGFP神经嵴衍生细胞。
这些结果表明，脐动脉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潜能。谱系追踪数据表明，p75NTR细胞可能源自神经嵴。
