Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly consider...Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.展开更多
AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （...AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （rFLDC） were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS： rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal （CD73, CD90, vimentin, m-smooth muscle actin）, hepatocyte （UGTIA1, CK8） and biliary （CK19） markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression （albumin, tryptophan 2,3-di- oxygenase, G6Pase） correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION： Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.展开更多
文摘Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.
基金Supported by Fonds pour la formation à la recherche dans l’industrie et dans l’agriculture (FRIA)
文摘AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （rFLDC） were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS： rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal （CD73, CD90, vimentin, m-smooth muscle actin）, hepatocyte （UGTIA1, CK8） and biliary （CK19） markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression （albumin, tryptophan 2,3-di- oxygenase, G6Pase） correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION： Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.
