Skip to main content
SpringerLink
Log in

The subtype CD200-positive, chorionic mesenchymal stem cells from the placenta promote regeneration of human hepatocytes

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Human placental mesenchymal stem cells (hPMSCs), for the treatment of fulminant hepatic failure, have been widely studied. Only a few studies have investigated the effect of the subtype CD200+hPMSCs on regeneration of human hepatocytes. CD200+hPMSCs can down-regulate activity of several immunocytes and suppress TNF-α secretion from macrophages via the CD200-CD200R axis. We have investigated the influence of CD200-positive human placenta chorionic mesenchymal stem cells (CD200+hPCMSCs) on metabolism, proliferation and apoptosis of human hepatocytes in vitro. CD200+hPCMSCs promote urea synthesis, albumin secretion and hepatocytes proliferation at co-culture ratios of 1:1 and 3:1. Additionally, CD200+hPCMSCs inhibit hepatocyte apoptosis via up-regulation of an anti-apoptotic protein, Bcl-xL. Thus, CD200+hPCMSCs can provide supportive benefit for the regeneration of human hepatocytes and also have immunosuppressive properties. Therefore, CD200+hPCMSCs may be an ideal candidate for stem cell-based therapy in hepatic failure.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abumaree MH, Al Jumah MA, Kalionis B, Jawdat D, Al Khaldi A, AlTalabani AA, Knawy BA (2013) Phenotypic and functional characterization of mesenchymal stem cells from chorionic villi of human term placenta. Stem Cell Rev 9:16–31

    Article  CAS  PubMed  Google Scholar 

  • Bardelli A, Longati P, Albero D, Goruppi S, Schneider C, Ponzetto C, Comoglio PM (1996) HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death. EMBO J 15:6205–6212

    CAS  PubMed Central  PubMed  Google Scholar 

  • Block GD, Locker J, Bowen WC et al (1996) Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium. J Cell Biol 132:1133–1149

    Article  CAS  PubMed  Google Scholar 

  • Chastre A, Bélanger M, Beauchesne E, Nguyen BN, Desjardins P, Butterworth RF (2012) Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications. PLoS One 7:e49670

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gómez-Aristizábal A, Keating A, Davies JE (2009) Mesenchymal stromal cells as supportive cells for hepatocytes. Mol Ther 17:1504–1508

    Article  PubMed Central  PubMed  Google Scholar 

  • Jung J, Choi JH, Lee Y, Park JW, Oh IH, Hwang SG, Kim KS, Kim GJ (2013) Human placenta-derived mesenchymal stem cells promote hepatic regeneration in CCl4-injured rat liver model via increased autophagic mechanism. Stem Cells 8:1584–1596

    Article  Google Scholar 

  • Lin H, Xu R, Zhang Z, Chen L, Shi M, Wang FS (2011) Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases. Cell Mol Immunol 8:19–22

    Article  CAS  PubMed  Google Scholar 

  • Nagaki M, Iwai H, Naiki T, Ohnishi H, Muto Y, Moriwaki H (2000) High levels of serum interleukin-10 and tumor necrosis factor–alpha are associated with fatality in fulminant hepatitis. J Infect Dis 182:1103–1108

    Article  CAS  PubMed  Google Scholar 

  • Najar M, Raicevic G, Jebbawi F et al (2012) Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes. Immunol Lett 146:50–56

    Article  CAS  PubMed  Google Scholar 

  • Nishino M, Iimuro Y, Ueki T, Hirano T, Fujimoto J (2008) Hepatocyte growth factor improves survival after partial hepatectomy in cirrhotic rats suppressing apoptosis of hepatocytes. Surgery 144:374–384

    Article  PubMed  Google Scholar 

  • Parekkadan B, van Poll D, Suganuma K, Carter EA, Berthiaume F, Tilles AW, Yarmush ML (2007) Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One 2:e941

    Article  PubMed Central  PubMed  Google Scholar 

  • Pietilä M, Lehtonen S, Tuovinen E et al (2012) CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells. PLoS One 7:e31671

    Article  PubMed Central  PubMed  Google Scholar 

  • Puglisi MA, Tesori V, Lattanzi W et al (2011) Therapeutic implications of mesenchymal stem cells in liver injury. J Biomed Biotechnol 2011:860578

    Article  PubMed Central  PubMed  Google Scholar 

  • Rygiel TP, Meyaard L (2012) CD200R signaling in tumor tolerance and inflammation: a tricky balance. Curr Opin Immunol 24:233–238

    Article  CAS  PubMed  Google Scholar 

  • Sun R, Jaruga B, Kulkarni S, Sun H, Gao B (2005) IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: regulation by SOCS3. Biochem Biophys Res Commun 338:1943–1949

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Li J, Pan X et al (2013) Co-culture with mesenchymal stem cells enhances metabolic functions of liver cells in bioartificial liver system. Biotechnol Bioeng 110:958–968

    Article  CAS  PubMed  Google Scholar 

  • Zhang D, Jiang M, Miao D (2011) Transplanted human amniotic membrane-derived mesenchymal stem cells ameliorate carbon tetrachloride-induced liver cirrhosis in mouse. PLoS One 6:e16789

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang Z, Lin H, Shi M et al (2012) Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 2:112–120

    Article  CAS  Google Scholar 

  • Zimmerman HW, Trautwein C, Tacke F (2012) Functional role of monocytes and macrophages for the inflammatory response in acute liver injury. Front Physiol 3:56

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the Tianjin Science and Technology commission funded key project (No. 11JCYBJC27700) and the Key Research Project of Tianjin Healthy Bureau (11KG112).

Author information

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The Third Central Clinical College of Tianjin Medical University, Tianjin, China

    Jian Wang & Yong Huang

  2. Key Laboratory of Artificial Cell, Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China

    Zhengyan Zhu, Peng Wang, Ying Luo, Yingtang Gao & Zhi Du

  3. Department of Hepatobiliary Surgery, The Third Central Houspital of Tianjin, Tianjin, 300170, China

    Zhi Du

Authors
  1. Jian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhengyan Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yingtang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhi Du
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhi Du.

Additional information

Jian Wang and Zhengyan Zhu contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1

Characters of hPCMSCs: a The phenotype of hPCMSCs, scale bar is 30 μm. b hPCMSCs were cultivated for approx. 3 days and morphology assessed by microscopy at 400 times, c cultured for 10 days with microscopy at 200 times and d one month under microscopy at 100 times (TIFF 3104 kb)

Supplementary material 2

CD200+hPCMSCs were sorted in the system of magnetic sorting: a isotype control, b the level of CD200+hPCMSCs before the magnetic extraction, c the level of CD200+hPCMSCs ofter the magnetic extraction (TIFF 601 kb)

Supplementary material 3

CD200+hPCMSCs inhibit apoptosis in TNF-α/Act-D induced human HL7702 hepatocytes. Microscope observation of HL7702 hepatocytes apoptosis managed with TNF-α/Act-D for 24 h. a Control group, b Apoptosis group, c Anti-apoptosis groups (TIFF 7022 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Zhu, Z., Huang, Y. et al. The subtype CD200-positive, chorionic mesenchymal stem cells from the placenta promote regeneration of human hepatocytes. Biotechnol Lett 36, 1335–1341 (2014). https://doi.org/10.1007/s10529-014-1468-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-014-1468-7

Keywords

Search

Navigation