In Vitro Differentiation of Human Placenta‐Derived Multipotent Cells into Hepatocyte‐Like Cells

Abstract

Multipotent cells isolated from human term placenta (placenta-derived multipotent cells [PDMCs]) have been known to be able to differentiate into mesodermal lineage cells, including adipocytes and osteoclasts. The low infection rate and young age of placenta compared with other tissue origins of adult stem cells make theses cells attractive target for cell-based therapy. However, the differentiation potential of PDMCs toward hepatic cells has not been evaluated yet. In this study, we cultivated PDMCs with hepatic differentiation medium to evaluate the ability of these cells in differentiating toward hepatic cells. After treatment, the morphologies of differentiated PDMCs changed to polygonal epithelial cell-like. The differentiated cells not only show the hepatocyte-like morphologies but also express hepatocyte-specific markers, including albumin and cytokeratin 18. The bioactivity assays revealed that these hepatocyte-like cells could uptake lipoprotein and store glycogen. Furthermore, the addition of rifampicin increased the gene expression of CYP3A4, which is similar with the activities of human liver cells. According to our previous results, PDMCs were capable of differentiating into mesodermal and ectodermal lineage cells. Our results indicate that PDMCs can differentiate into three germ layer cells, which is similar to embryonic stem cells. In conclusion, placenta might be an easily accessible source for progenitor cells that are capable of differentiating toward hepatocyte-like cells in vitro.

Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells

“…Banas et al (2007) reported hepatogenic differentiation of AT-MSCs from CD105 + AT-MSCs. Other MSCs from amniotic fluid and placenta have been also reported to differentiate into functional HLCs (Chien et al, 2006;de Coppi et al, 2007). In this study, MenSCs were induced to differentiate into heoatocytes with a cocktail of HGF, FGF-4, and OSM (Chen et al, 2007;Li J. et al, 2010).…”

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.…”

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

“…Transcriptional activation by HNF4␣ is mediated by its binding as a homodimer to direct repeat-1 promoter sequences of target genes (5). Genes transactivated by HNF4␣ encode various transcription factors, enzymes, and proteins involved in numerous processes, including hematopoiesis, blood coagulation/fibrinolysis, together with liver development and function (5)(6)(7)(8)(9). Conversely, molecular defects in HNF4␣ expression may provoke major disorders as noted in late-onset type 2 diabetes (10, 11) as well as in maturity-onset diabetes of the young 1, a disorder characterized by autosomal dominant inheritance and impaired glucose-stimulated insulin secretion from pancreatic ␤-cells (12,13).…”