Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes

Kang, X.; Zang, Wei-Jin; Bao, Lijun; Li, Dongling; Song, Taek Lyul; Xu, Xiaoli; Yu, Xin

doi:10.3748/wjg.v11.i47.7461

Cited by 47 publications

(17 citation statements)

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“…MSCs from the three sources when submitted to the hepatocyte differentiation protocol lost fibroblastic morphology and acquired a polygonal shape, with a more prominent central nucleus, similar to normal hepatocytes, according to the results obtained by other authors [29,30,47].…”

Section: Discussionsupporting

confidence: 79%

“…Selected genes were also not always the same, and, sometimes, gene expression was analyzed by means of different methods. Besides, the gene expression profile is not identical among all the hepatocytes [5,6,20,29,30,47,48].…”

Section: Discussionmentioning

confidence: 96%

“…The transplant was performed only with U-MSCs and DHLCs from AT and BM because of difficulties in expanding UCB-MSCs in the early MSC differentiation process, as already described in the literature by Kang et al, [47] in 2005 and Scheers et al [51] in 2013.…”

Section: Discussionmentioning

confidence: 98%

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Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis

et al. 2015

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 96%

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Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis

et al. 2015

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“…Glycogen is secreted in differentiated cells starting from day 14 [6] or from days 24-28 [8]. In our experiments, solitary cells positively stained with Schiff reagent were detected after 7 days of differentiation.…”

Section: Resultsmentioning

confidence: 90%

“…Mature differentiated cells were characte ri zed by the presence of numerous granules in the cytoplasm [9]. Previous studies showed the appearance of small round cells among umbilical cord blood MSC after 1 week of differentiation [6]. By day 28, about 64% cells were small, round, epithelioid, while in the control all cells had a fi broblast-like shape.…”

Section: Resultsmentioning

confidence: 99%

Hepatogenic Potential of Human Bone Marrow and Umbilical Cord Blood Mesenchymal Stem Cells

et al. 2011

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Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep

et al. 2007

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Alternative methods to whole liver transplantation require a suitable cell that can be expanded to obtain sufficient numbers required for successful transplantation while maintaining the ability to differentiate into hepatocytes. Mesenchymal stem cells (MSCs) possess several advantageous characteristics for cell-based therapy and have been shown to be able to differentiate into hepatocytes. Thus, we investigated whether the intrahepatic delivery of human MSCs is a safe and effective method for generating human hepatocytes and whether the route of administration influences the levels of donorderived hepatocytes and their pattern of distribution throughout the parenchyma of the recipient's liver. Human clonally derived MSCs were transplanted by an intraperitoneal (n ‫؍‬ 6) or intrahepatic (n ‫؍‬ 6) route into preimmune fetal sheep. The animals were analyzed 56-70 days after transplantation by immunohistochemistry, enzyme-linked immunosorbent assay, and flow cytometry. The intrahepatic injection of human MSCs was safe and resulted in more efficient generation of hepatocytes (12.5% ؎ 3.5% versus 2.6% ؎ 0.4%). The animals that received an intrahepatic injection exhibited a widespread distribution of hepatocytes throughout the liver parenchyma, whereas an intraperitoneal injection resulted in a preferential periportal distribution of human hepatocytes that produced higher amounts of albumin. Furthermore, hepatocytes were generated from MSCs without the need to first migrate/lodge to the bone marrow and give rise to hematopoietic cells. Conclusion: Our studies provide evidence that MSCs are a valuable source of cells for liver repair and regeneration and that, by the alteration of the site of injection, the generation of hepatocytes occurs in different hepatic zones, suggesting that a combined transplantation approach may be necessary to successfully repopulate the liver with these cells. (HEPATOLOGY 2007;46:1935-1945 T he maintenance of cellular homeostasis within the normal liver and during liver regeneration is provided by mature hepatocytes and cholangiocytes and by the intrahepatic (IH) stem cell compartment located in the canals of Hering and the intralobular bile ducts. 1 Recently, another potential source of cells able to provide liver cell replacement has been identified. These stem/progenitor cells consist of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) that reside within the bone marrow (BM) but can reach the liver through the circulatory system. [2][3][4][5][6][7][8][9][10][11][12] Because it is clearly evident that the shortage of available human donor organs cannot meet the needs of all the patients awaiting liver transplantation, alternatives to whole-organ replacement are urgently needed. Cell-based treatments, with cells of either hepatic or extrahepatic origin that would be able to repopulate and re-establish a functional liver after administration, could serve as a possible alternative to wholeorgan transplantation.In order to attain this goal, several questions, such as the sour...

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Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes

Abstract: E L S E V I E R • BASIC RESEARCH •and HGF, and was higher (54.28±3.11 µg/L) on d 28 (t = 13.493, P <0.01). Albumin increased significantly on d 16 (t = 6.68, P <0.01) to 1.02±0.15 µg/mL, and to 3.63±0.30 μg/mL on d 28 (t = 11.748, P <0.01). Urea

Cited by 47 publications

References 31 publications

Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis

Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis

Hepatogenic Potential of Human Bone Marrow and Umbilical Cord Blood Mesenchymal Stem Cells

Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep

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