Modification of Histone Acetylation Facilitates Hepatic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

Abstract

The multi-potentiality of mesenchymal stem cells makes them excellent options for future tissue engineering and clinical therapy, including liver injury. In this study, we investigated the effects of valproic acid (VPA), a direct inhibitor of histone deacetylase (HDAC), on the hepatic differentiation of human bone marrow mesenchymal stem cells (BMMSCs). The cells were found to differentiate into a more homogeneous hepatocyte-like population when pretreated with 5 mM VPA for 72 h. The expression of liver-specific markers was significantly upregulated in the VPA-treated group at the mRNA and protein levels. VPA treatment also significantly enhanced the hepatic functions of the differentiated cells, including glycogen storage, cytochrome P450 activity, AFP and ALB synthesis, and urea production. Further analysis showed that treatment with 5 mM of VPA for 72 h greatly improved the histones H3 and H4 acetylation. These results demonstrated that VPA could considerably improve the hepatic differentiation of human BMMSCs, probably because the chromatin-acetylated state changes upon VPA treatment through its HDAC inhibitory effect. Thus, this study provides a direct research model for producing human hepatocytes for clinical purposes.

Human endometrial stem cells differentiation into functional hepatocyte‐like cells

“…Our study, in serological functional assay, was proved the hEnSCs‐derived hepatocyte‐like cells synthesized both alpha‐fetoprotein and albumin. In a similar manner, some researchers were achieved functional hepatocyte derived from adult stem cells using sequential treatment with factors (Dong et al, ; Kazemnejad et al, ; Hashemi et al, ; No et al, ). These differentiated cells had hepatocyte cells feature comprising alpha‐fetoprotein, albumin, urea secretion, glycogen storage, indocyanine green uptake.…”

Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats

“…Bar 25 lm (Color figure online) apoptosis of tumor cells, increases cancer cell immunogenicity and inhibits angiogenesis and metastasis [43]. An increasing body of study demonstrates that VPA facilitates stem cell differentiation, such as hematopoietic stem cells [44], bone marrow-derived MSCs [45] and ESCs [46]. Abematsu et al [47] reported that VPA treatment promoted the differentiation of transplanted NSCs into neurons rather than glial cells in SCI.…”

Bone Marrow-Derived Mononuclear Cells Differentiate into Hepatocyte-Like Cells within Few Hrs without Fusion

“…In vitro differentiation is usually obtained by the use of growth factors, especially Hepatocyte Growth Factor (HGF), although quite a number of differences exist between protocols [19,[23][24][25]. Some authors have shown differentiation also with hepatocyte conditionedmedium [21] or serum from patients with hepatitis B virus-associated liver cirrhosis [35], co-culture with hepatocytes [36][37][38] or liver fragments [39] from healthy or injured animals.…”

“…Moreover, BMMC are characterized by their ability to differentiate into several functional mature cell types both in vivo and in vitro, including cardiomyocytes [7,8], endothelial cells [9], neurons [10,11] and hepatocytes [12][13][14][15][16][17][18]. In addition, many groups have developed protocols for the in vitro differentiation of bone marrow-derived cells into hepatocyte-like cells [19][20][21][22][23][24]. Although bone marrow mononuclear fraction is used for in vivo transplantation, in vitro protocols usually work with Mesenchymal Stem Cells (MSC) [19,[23][24][25].…”

“…In addition, many groups have developed protocols for the in vitro differentiation of bone marrow-derived cells into hepatocyte-like cells [19][20][21][22][23][24]. Although bone marrow mononuclear fraction is used for in vivo transplantation, in vitro protocols usually work with Mesenchymal Stem Cells (MSC) [19,[23][24][25].…”