Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage.

Cristiana Leite,Joana Paes De Faria,Francisco Dos Santos,Carla M P Cardoso,Margarida Vieira,Artur Paiva,Tânia Lourenço,N Tatiana Silva,Joaquim M S Cabral,Joaquim M S Cabral,Sandrine Mendes,João B Relvas,Cláudia L Da Silva,Cláudia L Da Silva,Pedro Z Andrade,Pedro Z Andrade,Mário Grãos,Andreia Ribeiro,Rafael Linden

doi:10.1371/journal.pone.0111059

Cristiana Leite, Joana Paes De Faria + Show 17 more

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https://doi.org/10.1371/journal.pone.0111059

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Abstract

Mesenchymal stem cells (MSCs) are viewed as safe, readily available and promising adult stem cells, which are currently used in several clinical trials. Additionally, their soluble-factor secretion and multi-lineage differentiation capacities place MSCs in the forefront of stem cell types with expected near-future clinical applications. In the present work MSCs were isolated from the umbilical cord matrix (Wharton's jelly) of human umbilical cord samples. The cells were thoroughly characterized and confirmed as bona-fide MSCs, presenting in vitro low generation time, high proliferative and colony-forming unit-fibroblast (CFU-F) capacity, typical MSC immunophenotype and osteogenic, chondrogenic and adipogenic differentiation capacity. The cells were additionally subjected to an oligodendroglial-oriented step-wise differentiation protocol in order to test their neural- and oligodendroglial-like differentiation capacity. The results confirmed the neural-like plasticity of MSCs, and suggested that the cells presented an oligodendroglial-like phenotype throughout the differentiation protocol, in several aspects sharing characteristics common to those of bona-fide oligodendrocyte precursor cells and differentiated oligodendrocytes.

Highlights

Mesenchymal stem cells (MSCs), known as mesenchymal stromal cells, are defined as multipotent adult stem cells, possessing self-renewal capacity and multilineage differentiation potential [1,2]
Despite controversy about MSCs differentiating into neural-like cellular fates, compelling evidence has shown that MSCs express neuroectodermal markers, like nestin [8,10,11,12,13] and have at least a partial neural crest, neuroepithelial origin [14,15], suggesting plasticity towards neural-like lineages, opening research avenues for the treatment of distinct neurodegenerative diseases [16,17]
The results presented here suggest that umbilical cord matrix mesenchymal stem cells (UCM-MSCs) possess a certain degree of plasticity to differentiate into neural-like cells, and subsequently into cells with phenotypic characteristics of oligodendrocyte precursors and immature oligodendrocytes

Summary

Introduction

Mesenchymal stem cells (MSCs), known as mesenchymal stromal cells, are defined as multipotent adult stem cells, possessing self-renewal capacity and multilineage differentiation potential [1,2]. Several reports in the literature have shown the potential of MSCs to differentiate into neural stem-like cells [7,8,9]. Despite controversy about MSCs (a mesenchymal cell type) differentiating into neural-like cellular fates, compelling evidence has shown that MSCs express neuroectodermal markers, like nestin [8,10,11,12,13] and have at least a partial neural crest, neuroepithelial origin [14,15], suggesting plasticity towards neural-like lineages, opening research avenues for the treatment of distinct neurodegenerative diseases [16,17]. MSCs have been rather explored in terms of neuronal-like differentiation [8,13,18,19,20], but the first reports addressing oligodendrocyte-like specification were only published recently [21,22].

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