Skip to main content

Advertisement

Log in

Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo

  • Report
  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Although human amniotic fluid is an attractive source of multipotent stem cells, the potential of amniotic fluid stem cells (AFSCs) to differentiate into hepatic cells has not been extensively evaluated. In this study, we examined whether human AFSCs can differentiate into a hepatic cell lineage in vitro and in vivo. After being treated with cytokines (fibroblast growth factor 4, basic fibroblast growth factor, hepatocyte growth factor, and oncostatin), AFSCs developed a morphology similar to that of hepatocytes. RT-PCR and immunofluorescence analysis showed that the treated AFSCs expressed the hepatocyte-specific markers albumin, cytokeratin 18, and alpha-fetoprotein. The differentiated cells also developed hepatocyte-specific functions, i.e., they secreted albumin, absorbed indocyanine green, and stored glycogen. When transplanted into CCl4-injured immunodeficient mice, undifferentiated AFSCs were integrated into the liver tissue, and they expressed markers characteristic of mature human hepatocytes. Although integration of AFSCs into the liver was limited (0.1–0.3% of hepatocytes), histological analysis showed that the recipient mice recovered more rapidly from CCl4 injury than CCl4-injured mice that did not receive AFSCs. AFSCs can differentiate into hepatocyte-like cells in vitro and in vivo and can represent an easily accessible source of progenitor cells for hepatocyte regeneration and liver cell transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1.
Figure 2.
Figure 3.

Similar content being viewed by others

References

  • Bansal M. B.; Kovalovich K.; Gupta R. et al. Interleukin-6 protects hepatocytes from CCl4-mediated necrosis and apoptosis in mice by reducing MMP-2 expression. J. Hepatol. 42: 548–556; 2005.

    Article  PubMed  CAS  Google Scholar 

  • Bouchereau M.; Gervais M. K.; Sideris L. et al. Hepatic necrosis and hemorrhage following hyperthermic intraperitoneal chemotherapy with oxaliplatin: a review of two cases. J. Gastrointest. Oncol. 2: 113–116; 2011.

    Google Scholar 

  • Cai J.; Zhao Y.; Liu Y. et al. Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 45: 1229–1239; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Carraro G.; Perin L.; Sedrakyan S. et al. Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages. Stem. Cells. 26: 2902–2911; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Chiavegato A.; Bollini S.; Pozzobon M. et al. Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. J. Mol. Cell. Cardiol. 42: 746–759; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Cipriani S.; Bonini D.; Marchina E. et al. Mesenchymal cells from human amniotic fluid survive and migrate after transplantation into adult rat brain. Cell. Biol. Int. 31: 845–850; 2007.

    Article  PubMed  CAS  Google Scholar 

  • De Coppi P.; Bartsch Jr. G.; Siddiqui M. M. et al. Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 25: 100–106; 2007.

    Article  PubMed  Google Scholar 

  • Gagandeep S.; Rajvanshi P.; Sokhi R. P. et al. Transplanted hepatocytes engraft, survive, and proliferate in the liver of rats with carbon tetrachloride-induced cirrhosis. J. Pathol. 191: 78–85; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Gang E. J.; Bosnakovski D.; Figueiredo C. A. et al. SSEA-4 identifies mesenchymal stem cells from bone marrow. Blood 109: 1743–1751; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Gupta S.; Rajvanshi P.; Irani A. N. et al. Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats. J. Pathol. 190: 203–210; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Hay D. C.; Zhao D.; Ross A. et al. Direct differentiation of human embryonic stem cells to hepatocyte-like cells exhibiting functional activities. Cloning. Stem. Cells. 9: 51–62; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Henderson J. K.; Draper J. S.; Baillie H. S. et al. Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens. Stem. Cells. 20: 329–337; 2002.

    Article  PubMed  CAS  Google Scholar 

  • In’t Anker P. S.; Scherjon S. A.; Kleijburg-vanderKeur C. et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem. Cells. 22: 1338–1345; 2004.

    Article  Google Scholar 

  • Kaido T.; Yamaoka S.; Tanaka J. et al. Continuous HGF supply from HGF-expressing fibroblasts transplanted into spleen prevents CCl4-induced acute liver injury in rats. Biochem. Biophys. Res. Commun. 218: 1–5; 1996.

    Article  PubMed  CAS  Google Scholar 

  • Kakinuma S.; Tanaka Y.; Chinzei R. et al. Human umbilical cord blood as a source of transplantable hepatic progenitor cells. Stem. Cells. 21: 217–227; 2003.

    Article  PubMed  Google Scholar 

  • Kamada Y.; Yoshida Y.; Saji Y. et al. Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice. Am. J. Physiol. Gastrointest. Liver. Physiol. 296: G157–G167; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Kim J.; Lee Y.; Kim H. et al. Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells. Cell. Prolif. 40: 75–90; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Naugler W. Hepatocellular carcinoma: targeted therapy and multidisciplinary care—Kelly M. McMasters and Jean-Nicolas Vauthey, editors. J. Gastrointest. Oncol. 2: 122; 2011.

    Google Scholar 

  • Nussler A.; Konig S.; Ott M. et al. Present status and perspectives of cell-based therapies for liver diseases. J. Hepatol. 45: 144–159; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Ochenashko O. V.; Nikitchenko Y. V.; Volkova N. A. et al. Functional hepatic recovery after xenotransplantation of cryopreserved fetal liver cells or soluble cell-factor administration in a cirrhotic rat model: are viable cells necessary? J. Gastroenterol. Hepatol. 23: e275–e282; 2008.

    Article  PubMed  Google Scholar 

  • Ochenashko O. V.; Volkova N. A.; Mazur S. P. et al. Cryopreserved fetal liver cell transplants support the chronic failing liver in rats with CCl4-induced cirrhosis. Cell. Transplant. 15: 23–33; 2006.

    Article  PubMed  Google Scholar 

  • Perin L.; Sedrakyan S.; Da Sacco S. et al. Characterization of human amniotic fluid stem cells and their pluripotential capability. Methods. Cell. Biol. 86: 85–99; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Sakai Y.; Jiang J.; Kojima N. et al. Enhanced in vitro maturation of fetal mouse liver cells with oncostatin M, nicotinamide, and dimethyl sulfoxide. Cell. Transplant. 11: 435–441; 2002.

    PubMed  CAS  Google Scholar 

  • Schmidt D.; Achermann J.; Odermatt B. et al. Cryopreserved amniotic fluid-derived cells: a lifelong autologous fetal stem cell source for heart valve tissue engineering. J. Heart. Valve. Dis. 17: 446–455; 2008.

    PubMed  Google Scholar 

  • Schwartz R. E.; Reyes M.; Koodie L. et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Invest. 109: 1291–1302; 2002.

    PubMed  CAS  Google Scholar 

  • Snykers S.; Vanhaecke T.; Papeleu P. et al. Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicol. Sci. 94: 330–341; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Tsai M. S.; Lee J. L.; Chang Y. J. et al. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum. Reprod. 19: 1450–1456; 2004.

    Article  PubMed  Google Scholar 

  • Yamada T.; Yoshikawa M.; Kanda S. et al. In vitro differentiation of embryonic stem cells into hepatocyte-like cells identified by cellular uptake of indocyanine green. Stem. Cells. 20: 146–154; 2002.

    Article  PubMed  Google Scholar 

  • Yan Y.; Xu W.; Qian H. et al. Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo. Liver. Int. 29: 356–365; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Zheng Y. B.; Gao Z. L.; Xie C. et al. Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study. Cell. Biol. Int. 32: 1439–1448; 2008.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ya-li Li or Xue-tao Pei.

Additional information

Editor: T. Okamoto

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, H., Liu, Dq., Li, Bw. et al. Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo. In Vitro Cell.Dev.Biol.-Animal 47, 601–608 (2011). https://doi.org/10.1007/s11626-011-9450-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-011-9450-3

Keywords

Navigation