Possible directions of human cord blood mononuclear cells differentiation in the regenerating rat liver
- Authors: Andreeva D.I1,2, Gazizov I.M1,2, Ylmaz T.S1, Kaligin M.S1,2, Gumerova A.A2, Kiyasov A.P2
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Affiliations:
- Kazan State Medical University
- Kazan Federal University
- Issue: Vol 8, No 3 (2013)
- Pages: 95-100
- Section: Articles
- URL: https://genescells.ru/2313-1829/article/view/120567
- DOI: https://doi.org/10.23868/gc120567
- ID: 120567
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Abstract
It is known that human cord blood hematopoietic stem cells (HSC) are able to differentiate into hepatocytes. This ability can be widely used in treatment of various liver diseases. However, there are some genetic diseases of liver, when the application of autologous stem cells is not possible. So it could be very helpful to develop methods of genetic modification of stem/progenitor cells. However, it should be proved that genetic modification does not change the properties of HSC. We performed partial hepatectomy for the white mongrel male rats and injected human umbilical cord blood mononuclear cells transfected by gene of green fluorescent protein (GFP) into the spleen. Paraffin sections of the liver were stained with antibodies to stem cell factor receptor, human leukocyte antigen, a-smooth muscle actin, enhanced GFP, cytokeratin 19, hepatocyte specific antigen, human a-fetoprotein. Also we used a double-immunohistochemical staining to detect expression of stem cell factor receptor and desmin, enhanced GFP and cytokeratin 19. Our study showed that human cord blood mononuclear cells transfected by gfp transplanted into the spleen of rats after partial hepatectomy migrated to the liver and acquired the phenotype of hepatocytes, cholangiocytes and sinusoidal cells. At the same time the differentiation of such transplanted cells into myofibroblasts, as it was previously shown, does not occur. Hepatoblasts and hepatocytes found in the liver of rats after transplantation of genetically modified and native cells express human hepatocyte specific antigen and a-fetoprotein that means they are functionally active.
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About the authors
D. I Andreeva
Kazan State Medical University; Kazan Federal UniversityKazan
I. M Gazizov
Kazan State Medical University; Kazan Federal UniversityKazan
T. S Ylmaz
Kazan State Medical UniversityKazan
M. S Kaligin
Kazan State Medical University; Kazan Federal UniversityKazan
A. A Gumerova
Kazan Federal UniversityKazan
A. P Kiyasov
Kazan Federal UniversityKazan
References
- Wiemann S.U., Satyanarayana A., Tsahuridu M. et al. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB 2002; 16: 935-42.
- Petersen B.E., Bowen W.C., Patrene K.D. et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284: 1168- 70.
- Cardoso A.A., Li M.L., Batard P. et al. Release from quiescence of CD 34+38- human umbilical cord blood cells reveals their potentiality to engraft adults. PNAS USA 1993; 90: 8707-11.
- Terai S., Sakaida I., Yamamoto N. et al. An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes. Biochem. 2003; 134: 551-8.
- Vassilopoulos G., Wang P.R., Russel D.W. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003; 422: 901-4.
- Hawley T.S., Hawley R.G., Totowa N.J. Methods in molecular biology: flow cytometry protocols, 2nd ed.: Humana Press Inc.; 2004.
- Rizvanov A.A., Kiyasov A.P., Gaziziov I.M. et al. Human umbilical cord blood cells transfected with VEGF, L1CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis - a novel approach in stem cell therapy. Neurochemistry International 2008; 53: 389-94.
- Higgins G.M., Anderson R.M. Experimental pathology of the liver: I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 1931; 12: 186-202.
- Michalopoulos G.K. Liver Regeneration. J. Cell. Physiol. 2007; 213: 286-300.
- Forbes S.J., Russo F.P., Rey V. et al. A significant proportion of myofibroblasts are of the bone marrow origin in human liver fibrosis. Gastroenterology 2004; 126: 955-63.
- Киясов А.П. Экспрессия десмина и цитокератинов № 8 и 18 в некроветворных клетках печени крыс. Онтогенез 1997; 28 (3): 217-22.
- Ishikawa T., Terai S., Urata Y. et al. Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes. Cell Tissue Res. 2006; 323: 221-32.
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