Abstract
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. 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 1 mM NaBu along with EGF and bFGF supplementation condition was appropriately pre-treated with hWJ-MSCs before hepatogenic differentiation. Furthermore, the hepatic differentiation medium with 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 hepatic differentiation medium with NaBu in the pre-treatment step can induce hWJ-MSC differentiation toward endodermal, hepatoblastic, and hepatic lineages. Therefore, the hepatic differentiation medium with NaBu pre-treatment for differentiating hWJ-MSCs could represent an alternative protocol for cell-based therapy and drug screening in clinical applications.
Highlights
The liver is the largest organ and essentially produces metabolites and detoxifying toxic substances
HWJ-mesenchymal stem cell (MSC) were characterized at passage 4 via immunophenotyping and multipotency assays (Figures S2 and S3)
Among hWJ-MSCs #1, hWJ-MSCs #2, and hWJ-MSCs #3, it was found that immunophenotyping and multipotency properties did not perform different patterns, while growth kinetics and hepatic differentiation by using immunofluorescence and Periodic acid-Schiff (PAS) staining of hWJ-MSCs #3 were greater exhibited expressions of hepatic-specific features than hWJ-MSCs #1 and hWJ-MSCs #2
Summary
The liver is the largest organ and essentially produces metabolites and detoxifying toxic substances. Hepatocytes can be gradually destroyed by toxic substances, which can lead to liver failure and death at the end-stages of liver diseases [1]. For such patients, treatments including orthotropic organ and cell transplantations have recently been pioneered. The shortage of organ donors and low quality of cultivated hepatocytes remain the major problems associated with these types of treatments [2,3]. Owing to these limitations, new alternative therapeutic approaches are required. Mesenchymal stem cell (MSC) biology has recently received increasing attention
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
