Effects of sodium butyrate on the differentiation of pancreatic and hepatic progenitor cells from mouse embryonic stem cells

Abstract

Recently significant progress has been made in differentiating embryonic stem (ES) cells toward pancreatic cells. However, little is known about the generation and identification of pancreatic progenitor cells from ES cells. Here we explored the influence of sodium butyrate on pancreatic progenitor differentiation, and investigated the different effects of sodium butyrate on pancreatic and hepatic progenitor formation. Our results indicated that different concentration and exposure time of sodium butyrate led to different differentiating trends of ES cells. A relatively lower concentration of sodium butyrate with shorter exposure time induced more pancreatic progenitor cell formation. When stimulated by a higher concentration and longer exposure time of sodium butyrate, ES cells differentiated toward hepatic progenitor cells rather than pancreatic progenitor cells. These progenitor cells could further mature into pancreatic and hepatic cells with the supplement of exogenous inducing factors. The resulting pancreatic cells expressed specific markers such as insulin and C-peptide, and were capable of insulin secretion in response to glucose stimulation. The differentiated hepatocytes were characterized by the expression of a number of liver-associated genes and proteins, and had the capability of glycogen storage. Thus, the current study demonstrated that sodium butyrate played different roles in inducing ES cells toward pancreatic or hepatic progenitor cells. These progenitor cells could be further induced into mature pancreatic cells and hepatocytes. This finding may facilitate the understanding of pancreatic and hepatic cell differentiation from ES cells, and provide a potential source of transplantable cells for cell-replacement therapies.

Obesity Determines the Immunophenotypic Profile and Functional Characteristics of Human Mesenchymal Stem Cells From Adipose Tissue

“…Cell-cell adhesion mediated by CD106 is known to be critical for T-cell activation and leukocyte recruitment to the site of inflammation, and, therefore, plays an important role in evoking effective immune responses. Moreover, CD106 is critical for MSC-mediated immunosuppression [44] and for the binding of hematopoietic progenitor cells [45]. Our data lead us to speculate that increased expression of HLA II/CD106 in a subpopulation of undifferentiated and differentiated hASCs, together with upregulated expression of CD49b in differentiated hASCs from obese individuals, could be related to the powerful immunosuppressive activity of hASCs.…”

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

“…Gene silencing associated with the aberrant methylation of promoter region of CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic events in the inactivation of tumor suppressor and other genes in human cancers. NaBu has been applied in cellular and molecular research (23,24), particularly in antitumor research (25)(26)(27)(28). It plays a vital role in vitamin D-induced apoptosis through PTEN upregulation, which has potential benefit in gastric cancer therapy (29).…”

In vitro hepatic differentiation of umbilical cord-derived mesenchymal stem cell

“…It is thought that HDAC inhibitor triggered epigenetic changes and influenced several key gene expressions [24]. Also the effect of DMSO on hepatic differentiation has not yet elucidated.…”

“…It is well known that TSA is one of the histone deacetylase (HDAC) inhibitors as like sodium butyrate. Sodium butyrate has been used in the hepatic terminal maturation of embryonic stem cells [21][22][23][24], although the precise role of HDAC inhibitor in the maturation is unclear.…”