Umbilical artery tissue contains p75 neurotrophin receptor-positive pericyte-like cells that possess neurosphere formation capacity and neurogenic differentiation potential

• Published in: Regenerative therapy Vol. 16; pp. 1 - 11
• Main Authors: Fujii-Tezuka, Rina, Ishige-Wada, Mika, Nagoshi, Narihito, Okano, Hideyuki, Mugishima, Hideo, Takahashi, Shori, Morioka, Ichiro, Matsumoto, Taro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2021; Japanese Society for Regenerative Medicine; Elsevier
• Subjects: Mesenchymal stem cells; Neural crest stem cells; Neurosphere; Original; p75 neurotrophin receptor; Umbilical cord; p75NTR; α-MEM; vWF; βME; EGFP; UA; UC; DMEM; NF200; MSCs; WJ; MAP2; FBS; ASMA; NG2; CFU-F; Mesenchymal stem cells; FSK; PBS; UV; NCSCs; TBS; p75 neurotrophin receptor; BDNF; EGF; Neurosphere; DAPI; GFAP; RA; FGF-2; PDGF; EdU; Umbilical cord; Neural crest stem cells; CFU-F, colony-forming unit fibroblast; GFAP, glial fibrillary acidic protein; EGF, epidermal growth factor; TBS, Tris-buffered saline; UV, umbilical vein; DMEM, Dulbecco's modified Eagle medium; PBS, phosphate-buffered saline; BDNF, bone-derived neurotrophic factor; α-MEM, alpha-modified minimum essential medium; DAPI, 4′,6-diamino-2-phenylindole; WJ, Wharton's jelly; EGFP, enhanced green fluorescent protein; p75NTR, p75 neurotrophin receptor; MAP2, microtubule-associated protein 2; NG2, neuron-glial antigen 2; NF200, neurofilament 200; FBS, fetal bovine serum; MSCs, mesenchymal stem cells; FGF-2, fibroblast growth factor-2; vWF, von Willebrand factor; UA, umbilical artery; ASMA, α-smooth muscle actin; βME, β-mercaptoethanol; NCSCs, neural crest-derived stem cells; RA, all-trans-retinoic acid; EdU, 5-ethynyl-2′-deoxyuridine; FSK, forskolin; UC, umbilical cord; PDGF, platelet-derived growth factor
• ISSN: 2352-3204; 2352-3204
• DOI: 10.1016/j.reth.2020.12.002

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.