Establishment of human hair follicle mesenchymal stem cells with overexpressed human hepatocyte growth factor

Document Type : Original Article


1 Department of Pediatrics, The Second Hospital of Jilin University, Changchun 130041, China

2 Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130041, China

3 The Ministry of Education Key Laboratory, The College of Basic Medical Sciences, of Jilin University, Changchun 130041, China


Objective(s): Chronic liver disease has become a major health problem that causes serious damage to human health. Since the existing treatment effect was not ideal, we need to seek new treatment methods.
Materials and Methods: We utilized the gene recombination technology to obtain the human hair mesenchymal stem cells which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we verified the property of transfected cells through detecting surface marker by flow cytometry.
Results: We show here establishment of the hHGF-overexpressing lentivirus vector, and successfully transfection to human hair follicle mesenchymal stem cells. The verified experiments could demonstrate the human hair follicle mesenchymal stem cells which have been transfected still have the properties of stem cells.
Conclusion: We successfully constructed human hair follicle mesenchymal stem cells which overexpression hHGF, and maintain the same properties compared with pro-transfected cells.


1. Neuberger J. An update on liver transplantation: A critical review. J Autoimmun 2016;66:51-9
2. Desai R, Neuberger J.Donor transmitted and de novo cancer after liver transplantation. World J Gastroentrol 2014; 20:6170–6179.
3. Yan L, Cai C, Li J, Xu S, Chang Q, Li Y, Wu B.Present status and perspectives of stem cell- based therapies for gastrointestinal diseases. Stem Cell Rev 2009; 5:278-282.
4. Ferrer JR, Chokechanachaisakul A, Wertheim JA. New tools in experimental cellular therapy for the treatment of liver diseases. Curr Transplant Rep 2015; 2:202-210.
5. Zhou H, Liu H, Ezzelarab M, Schmelzer E, Wang Y, Gerlach J, Gridelli B, Cooper DK. Experimental hepatocyte xenotransplantation-a comprehen-sive review of the literature. Xenotransplantation.2015;22:239-48.
6. Bhatia SN, Underhill GH, Zaret KS, Fox IJ. Cell and tissue engineering for liver disease. Sci Transl Med 2014; 6: 245sr2.
7. Ebrahimkhani MR, Neiman JA, Raredon MS, Hughes DJ, Griffith LG. Bioreactor technologies to support liver function in vitro. Adv Drug Deliv Rev 2014; 69-70:132-157.
8. Nakamura T, Mizuno S. The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proc Jpn Acad Ser B Phys Biol Sci 2010; 86:588-610.
9. Gómez-Aristizábal A, Keating A, Davies JE.Mesenchymal stromal cells as supportive cells for hepatocytes. Mol Ther 2009; 17:1504-1508.
10. Forte TM. Primary hepatocytes in mono-layer culture: a model for studies on lipoprotein metabolism. Annu Rev Physiol 1984; 46: 403–415.
11. Nakamura T1, Sakai K, Nakamura T, Matsumoto K. Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol 2011; 1:188-202.
12. Kaido T, Oe H, Yoshikawa A, Okajima A, Imamura M. Expressions of molecules associated with hepatocyte growth factor activation after hepatectomy in liver cirrhosis. Hepatogastroenterology 2004; 51:547-551.
13. Atta H, El-Rehany M, Hammam O, Abdel-Ghany H, Ramzy M, Roderfeld M, Roeb E, Al-Hendy A, Raheim SA, Allam H, Marey H. Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltrans-ferases repression. PLoS One 2014; 9:e112384.
14. Kim MD, Kim SS, Cha HY, Jang SH, Chang DY, et al. Therapeutic effect of hepatocyte growth factor-secre-ting mesenchymal stem cells in a rat model of liver fibrosis. Exp Mol Med 2014; 22;46:e110.
15. Seo KW, Sohn SY, Bhang DH, Nam MJ, Lee HW, Youn HY. Therapeutic effects of hepatocyte growth factor-overexpre ssing human umbilical cord blood-derived mesenchymal stem cells on liver fibrosis in rats. Cell Biol Int 2014; 38:106-116.
16. Xia JL, Dai C, Michalopoulos GK, Liu Y. Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation. Am J Pathol 2006; 168:1500-1512.
17. Waters James M, Richardson Gavin D, Jahoda Colin AB. Hair follicle stem cells. Semin Cell Dev Biol 2007; 18:245-254.
18. Anas El-Aneed. An overview of current delivery systems in cancer gene therapy. J Control Release 2004; 94:1-14.
19. Nakamura T, Nawa K and Ichihara A. Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun 1984; 122:1450–1459.
20. Gohda E, Tsubouchi H., Nakayama H, Hirono S, Sakiyama O,Takahashi K, et al. Purification and partial characterization ofhepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest 1988; 81:414–419.
21. Zarnegar R, Michalopoulos G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor forhepatocytes. Cancer Res 1989; 49:3314–3320.
22. Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989; 342:440–443.
23. Tashiro K, Hagiya M, Nishizawa T, Seki T, Shimonishi M, Shimizu S, et al. Deduced primary structure of rat hepatocyte growth factor and
expression of the mRNA in  rat tissues. Proc Natl Acad Sci U S A 1990; 87:3200–3204.
24. Nakamura T. Structure and function of hepatocyte growth factor . Prog Growth Factor Res 1991; 3:67–85.
25. Matsumoto K, Nakamura T. Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions . Crit Rev Oncog 1992; 3:27–54.
26. Birchmeier C, Gherardi E. Develop-mental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 1998; 8:404–410.
27.  Kellermann G, Boudechiche L, Weber A, Hadchouel M. Increased engraftment of hepatic progenitors after activation of the hepatocyte growth factor signaling pathway by protein transduction . Exp Biol Med  2009;  234:1102-1108.
28. Xue F, Takahara T, Yata Y, Kuwabara Y, Shinno E, Nonome K, et al. Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomy. Gut 2003; 52:694-700.
29. Yanagita K, Nagaike M, Ishibashi H, Niho Y, Matsumoto K, Nakamura T. Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs. Biochem Biophys Res Commun 1992; 182:802–809.
30. Hu JJ, Sun C, Lan L, Chen YW, Li DG. Therapeutic effect of transplanting β2m/Thy1+bone marrow-derived hepatocyte stem cells transduced with lentiviral-mediated HGF gene into CCl4-injured rats. J Gene Med2010; 12:244–254.