Hepatic stellate cells stimulate hepatocyte differentiation of rats bone marrow derived mesenchymalstem cells in vitro



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Abstract

Wide dissemination of chronic hepatitis and low
efficiency of their medication require development of new
approaches for treatment of this pathology. One of the most
perspective search directions is connected with stimulation
of mesenchymal stem cells differentiation into hepatocytes
by applying fibroblast growth factor 4 (FGF-4) and hepatocyte
growth factor (HGF), which determine primary differentiation
of anterior gut epithelial cells into hepatocytes during prenatal
ontogenesis in mammals. It is known that hepatic stellate cells
(HSC) are the natural source of these growth factors in the
liver and they are essential component of microenvironment
for differentiating epithelial cells during liver ontogenesis and
regeneration. The aim of this survey was to study the ability of
stimulation of bone marrow derived multipotent mesenchymal
cells (MMSC) hepatic differentiation by cultivation in the
hepatic stellate cells conditioned media. MMSC were cultivated
in various models: 1) in the media free of growth factors;
2) in the media by sequential exposure of growth factors;
3) in HSC conditioned media; 4) co-cultivation together with
HSC separated by semipermeable membrane on the boyden
chambers; 5) in the mixed co-culture. Results of the survey
showed that factors and cytokines, produced by HSC in the
media render significant effect on MMSC and lead to their
differentiation into hepatoblasts and hepatocytes with stable
expression (unlike expression of MMSC cultivated with growth
factors) of epithelial markers and ƒ-fetoprotein. Direct
intercellular contacts between MMSC and HSC in the mixed
co-culture stimulate bulk and apparent expression of hepatic
markers unlike in monoculter, but the phenomenon of cell
fusion was not detected. Thus, results of this study confirm
the hypothesis of the HSC role as an important element of
microenvironment for MMSC hepatic differentiation in vitro.

About the authors

A A Gumerova,

Trondin, I.M. Gazizov, D.I. Andreeva, M.S. Kaligin, A.A. Rizvanov, A.P. Kiasov

Trondin, I.M. Gazizov, D.I. Andreeva, M.S. Kaligin, A.A. Rizvanov, A.P. Kiasov

A K Shafigullina,

Kazan State Medical University, Kazan

Kazan State Medical University, Kazan

A A Trondin

I M Gazizov,

Kazan State Medical University, Kazan

Kazan State Medical University, Kazan

D I Andreeva,

Kazan State Medical University, Kazan

Kazan State Medical University, Kazan

M S Kaligin,

Kazan State Medical University, Kazan

Kazan State Medical University, Kazan

A A Rizvanov,

Kazan State Medical University, Kazan

Kazan State Medical University, Kazan

A P Kiasov

Kazan State Medical University, Kazan

Kazan State Medical University, Kazan

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