Differentiation of Human Mesenchymal Stem Cells from Wharton’s Jelly Towards Neural Stem Cells Using a Feasible and Repeatable Protocol

The transplantation of neural stem cells (NSCs) capable of regenerating to the cells of the central nervous system (CNS) is a promising strategy in the treatment of CNS diseases and injury. As previous studies have highlighted mesenchymal stem cells (MSCs) as a source of NSCs, this study aimed to develop a feasible, efficient, and reproducible method for the neural induction of MSCs isolated from Wharton’s jelly (hWJ-MSCs). We induced neural differentiation in a monolayer culture using epidermal growth factor, basic fibroblast growth factor, N2, and B27 supplements. This resulted in a homogenous population of proliferating cells that expressed certain neural markers at both the protein and mRNA levels. Flow cytometry and immunocytochemistry confirmed the expression of neural markers: nestin, sex-determining region Y (SRY) box 1 and 2 (SOX1 and SOX2), microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP). The qRT-PCR analysis revealed significantly enhanced expression of nestin and MAP2 in differentiated cells. This study confirms that it is possible to generate NSCs-like cells from hWJ-MSCs in a 2D culture using a practical method. However, the therapeutic effectiveness of such differentiated cells should be extended to confirm the terminal differentiation ability and electrophysiological properties of neurons derived from them.

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Transforming growth factor-beta 1 or ascorbic acid are able to differentiate Wharton’s jelly mesenchymal stem cells towards a smooth muscle phenotype

Bio-Medical Materials and Engineering ◽

10.3233/bme-171630 ◽

2017 ◽

Vol 28 (s1) ◽

pp. S101-S105 ◽

Cited By ~ 4

Author(s):

B. Mesure ◽

S. Huber-Villaume ◽

P. Menu ◽

É. Velot

Keyword(s):

Stem Cells ◽

Ascorbic Acid ◽

Mesenchymal Stem Cells ◽

Smooth Muscle ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Wharton’S Jelly ◽

Wharton's Jelly ◽

Growth Factor Beta

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Enhanced Hepatogenic Differentiation of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells by Using Three-Step Protocol

International Journal of Molecular Sciences ◽

10.3390/ijms20123016 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3016 ◽

Cited By ~ 1

Author(s):

Wachira Panta ◽

Sumeth Imsoonthornruksa ◽

Ton Yoisungnern ◽

Sanong Suksaweang ◽

Mariena Ketudat-Cairns ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Glycogen Storage ◽

Wharton’S Jelly ◽

Wharton's Jelly ◽

Lineage Differentiation ◽

Cell Based Therapy ◽

Hepatogenic Differentiation ◽

Pre Treatment

Currently, human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) are an attractive source of stem cells for cell-based therapy, owing to their ability to undergo self-renewal and differentiate into all mesodermal, some neuroectodermal, and endodermal progenies, including hepatocytes. Herein, this study aimed to investigate the effects of sodium butyrate (NaBu), an epigenetic regulator that directly inhibits histone deacetylase, on hepatic endodermal lineage differentiation of hWJ-MSCs. NaBu, at 1 mM, optimally promoted endodermal differentiation of hWJ-MSCs, along with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) supplementation (EGF + bFGF + 1 mM NaBu). CXCR4, HNF3β, SOX17 (endodermal), and GATA6 (mesendodermal) mRNAs were also up-regulated (p < 0.001). Immunocytochemistry and a Western blot analysis of SOX17 and HNF3β confirmed that the EGF + bFGF + 1 mM NaBu condition was appropriately pre-treated with hWJ-MSCs before hepatogenic differentiation. Furthermore, the hepatogenic medium + NaBu pre-treatment up-regulated hepatoblast (AFP and HNF3β) and hepatic (CK18 and ALB) markers, and increased the proportion of mature hepatocyte functions, including G6P, C/EBPα, and CYP2B6 mRNAs, glycogen storage and urea secretion. The hepatogenic medium + NaBu in the pre-treatment step can induce hWJ-MSC differentiation toward endodermal, hepatoblastic, and hepatic lineages. Therefore, the hepatogenic medium + NaBu pre-treatment for differentiating hWJ-MSCs could represent an alternative protocol for cell-based therapy and drug screening in clinical applications.

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