The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells. However, to improve the effectiveness of such treatment it is necessary to search for more optimal sources of progenitor cells, as well as to evaluate the possibility of using descendants of these cells differentiated in vitro. In this study we isolated stromal cells from the liver biopsies of three patients with alcoholic cirrhosis, conducted their morphological and phenotypic analysis, and evaluated the hepatic potential of these cells in vitro. The stromal cells isolated from fetal liver were used for comparison. The results of this can serve as a basis for the development of a new method for the treatment of end-stage liver disease. The stromal cells isolated from the liver biopsies for a long time proliferate in a culture and this which makes it possible to expand them to large amounts for subsequent differentiation into hepatocyte-like cells and autologous transplantation.
Pechen' obladaet vyrazhennoĭ sposobnost'iu k regeneratsii, kotoruiu v bol'shinstve sluchaev obespechivaiut gepatotsity. V usloviiakh ostrogo ili khronicheskogo povrezhdeniia regenerativnaia sposobnost' gepatotsitov sushchestvenno snizhaetsia. V chastnosti, pri alkogol'nom tsirroze, reparativnye mekhanizmy ne aktiviruiutsia, i takim patsientam mozhet pomoch' libo transplantatsiia organa, libo sovremennye metody regenerativnoĭ meditsiny. V klinicheskikh ispytaniiakh, provedennykh s uchastiem patsientov s razlichnymi formami bolezni pecheni, kotorym transplantirovali autologichnye stvolovye kletki kostnogo mozga, byli polucheny mnogoobeshchaiushchie rezul'taty. Odnako dlia povysheniia éffektivnosti takogo lecheniia neobkhodimo osushchestvliat' poisk bolee podkhodiashchikh istochnikov progenitornykh kletok. V dannoĭ rabote my vydelili stromal'nye kletki iz bioptatov pecheni donorov, bol'nykh alkogol'nym tsirrozom, proveli ikh morfologicheskiĭ i fenotipicheskiĭ analiz, a takzhe otsenili gepatogennyĭ potentsial étikh kletok in vitro. V kachestve sravneniia ispol'zovali stromal'nye kletki fetal'noĭ pecheni. Oba tipa kletok v khode gepatogennoĭ differentsirovki ékspressirovali markery gepatotsitov i sekretirovali al'bumin. Éti rezul'taty mogut sluzhit' osnovoĭ dlia razrabotki novogo metoda pri lechenii terminal'nykh stadiĭ zabolevaniĭ pecheni. Vydelennye iz bioptatov stromal'nye kletki dlitel'noe vremia proliferiruiut v kul'ture, chto daet vozmozhnost' poluchat' ikh bol'shie kolichestva dlia posleduiushcheĭ differentsirovki v gepatotsitopodobnye kletki i dlia autologichnoĭ transplantatsii.
Keywords: adult liver stromal cells; alcoholic cirrhosis; fetal liver stromal cells; hepatic differentiation; hepatocyte-like cells.