Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3β

Abstract

Human bone marrow-derived mesenchymal stem cells (BM-MSCs) are expected to be a potential source of cells for transplantation. Although recent reports have shown that isolated MSCs can differentiate into hepatocytes, the efficiency of differentiation is insufficient for therapeutic application. To circumvent this problem, it is necessary to understand the mechanisms of hepatic differentiation of human BM-MSCs. Hepatocyte nuclear factor 3␤ (HNF3␤), a forkhead/winged helix transcription factor, is essential for liver development. In the present study, we established a tetracycline (

Rejuvenating liver and pancreas through cell transdifferentiation

“…Though constantly under debate, there are accumulating evidences over the years supporting the hepatic transdifferentiation from MSC of different origins [5][6][7][8]. These hepatocyte-like cells transdifferentiated from MSC closely resemble hepatocyte characteristics in vitro.…”

The cyclin E regulator cullin 3 prevents mouse hepatic progenitor cells from becoming tumor-initiating cells

“…The hepatocyte-specific transcription factor PXR (29) was strongly induced at 48 hours after cultivation in differentiation medium, followed by the induction of liver-specific transcription factors such as HNF1/4α and CCAAT enhancer binding protein α (C/EBPα) and albumin (30) (Figure 3A). Importantly, upon differentiation, the vast majority of cells also changed their morphology from a small cell containing little cytoplasm to a cell that showed the typical hepatocyte morphology and glycogen deposition (Supplemental Figure 4A) (31). Next we determined the percentage of cells staining positive for γ-H2AX in the differentiating cells as compared with asynchronously growing Cul3-deficient progenitor cells.…”

The inhibitory effect of MSCs expressing TRAIL as a cellular delivery vehicle in combination with cisplatin on hepatocellular carcinoma

“…An immortalized human bone marrowderived MSCs lines UE7T-13 cells (JCRB 1154, JCRB Cell Bank), [44][45][46][47] the life span of which was prolonged by infecting retrovirus encoding human papillomavirus E7 and human telomerase reverse transcriptase (hTERT) was used in the present study. HCC cells line MHCC97-H (kindly provided by Prof. Zhao-You Tang, Liver Cancer Institute, Fudan University) 48 and MSCs were grown in Dulbecco's modified Eagle's medium with 10% fetal bovine serum and penicillin (100 U/ml)/ streptomycin (100 μg/ml) and were maintained at 37°C in a humidified atmosphere with 5% CO 2 .…”