Effects of growth factors on the growth and differentiation of mouse fetal liver epithelial cells in primary cultures

Kawasaki, Tatsuya; Tamura, Shinji; Kiso, Shinichi; Doi, Yoshinori; Yoshida, Yasuhiko; Kamada, Y.; Saeki, Ayuko; Saji, Yukiko; Matsuzawa, Yūji

doi:10.1111/j.1440-1746.2005.03812.x

Cited by 8 publications

(2 citation statements)

References 35 publications

(39 reference statements)

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“…To optimize the differentiation conditions, different combinations of cytokines and various coatings of the culture plates were tested. The growth factors chosen, HGF and FGF‐4, and the chemical DMSO were shown to play important roles in hepatocyte differentiation [51]. HGF, a growth factor produced by mesenchymal cells, plays a critical role in the development of liver cells [52], and the addition of HGF helps in driving stem cell differentiation toward hepatocyte‐like cells [17, 53].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…The purpose of this study was the development of a functional thermoresponsive cell culture system that maintains hepatocyte specific functions without non-parenchymal cells and allows for the recovery of a cell sheet. Under typical culture conditions of hepatocytes and their sheets, the addition of soluble EGF, a potent hepatocyte mitogen [16], [17], to the culture medium is essential for hepatocyte survival. Here, we utilize affinity-immobilization of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which has the ability to bind to heparin with a specific affinity interaction [18], [19], [20] on a heparin-modified thermoresponsive surface for the maintenance of hepatic function.…”

Section: Introductionmentioning

confidence: 99%

A heparin-modified thermoresponsive surface with heparin-binding epidermal growth factor-like growth factor for maintaining hepatic functions in vitro and harvesting hepatocyte sheets

Arisaka

Kobayashi

Ohashi

et al. 2016

Regenerative Therapy

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A heparin-modified thermoresponsive surface bound with heparin-binding epidermal growth factor-like growth factor (HB-EGF) was designed to allow creation of transferrable and functional hepatocyte sheets. A heparin-modified thermoresponsive surface was prepared by covalently tethering heparin onto poly( N -isopropylacrylamide- co -2-carboxyisopropylacrylamide)-grafted tissue culture polystyrene surfaces (Heparin-IC). HB-EGFs were able to stably bind to heparin-IC via affinity interaction. The survival of primary rat hepatocytes was maintained through HB-EGF-bound heparin-IC (HB-EGF/heparin-IC). Moreover, cultured rat primary hepatocytes on HB-EGF/heparin-IC exhibited higher albumin-secretion than hepatocytes cultured on PIPAAm-grafted and collagen-coated surfaces with soluble HB-EGF in the culture medium, regardless of whether soluble EGF was added. These results suggested that HB-EGF/heparin-IC is able to effectively maintain hepatic function via continuous signaling of HB-EGF. After a 4-day cultivation, the cultured hepatocytes on HB-EGF/heparin-IC detached as a cell sheet with fibronectin and HB-EGF only after the temperature was lowered to 20 °C. In addition, higher expression of hepatocyte-specific genes (albumin, hepatocyte nuclear factor 4 alpha, coagulation factor VII, and coagulation factor IX) in hepatocyte sheets was detected on HB-EGF/heparin-IC than on a PIPAAm surface with soluble HB-EGF, indicating that HB-EGF/heparin-IC suppressed the dedifferentiation of cultured hepatocytes. Hence, heparin-modified thermoresponsive surfaces bound with HB-EGF facilitate the fabrication of transferrable hepatocyte sheets with intact hepatic functions and have the potential to provide an in vitro culture system using functional hepatocyte sheet tissues, which may serve as an effective hepatocyte-based tissue engineering platform for liver disease treatments.

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Growth factor/heparin-immobilized collagen gel system enhances viability of transplanted hepatocytes and induces angiogenesis

Hou

Ijima

Takei

et al. 2011

Journal of Bioscience and Bioengineering

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Effects of growth factors on the growth and differentiation of mouse fetal liver epithelial cells in primary cultures

Abstract: Hepatocyte growth factor, HB-EGF, bFGF, EGF and TGF-alpha increased DNA synthesis of FLEC. HGF, HB-EGF, bFGF and EGF led to an increase in liver-specific gene expressions; and their effects on differentiation differ as a function of gestation age.

Cited by 8 publications

References 35 publications

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

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

A heparin-modified thermoresponsive surface with heparin-binding epidermal growth factor-like growth factor for maintaining hepatic functions in vitro and harvesting hepatocyte sheets

Growth factor/heparin-immobilized collagen gel system enhances viability of transplanted hepatocytes and induces angiogenesis

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