| There are differentiation grades of cells, from oosperm, embryonic stem cells and multipotential stem cells to mature cells which constitute adult tissues and organs in mammal ontogenesis.Are there any remnant stem cells of certain differentiation grades in adult tissues and organs after ontogenesis? It is generally accepted that physiologic or phathologic cell loss and regeneration are natural phenomena in the life process, and that stem cells in hermatopoietic system, epidermis and intestinal epithelia play an important role in such regeneration. But is it the case with the liver?The liver is reported to regenerate completely from some physical or chemical injuries. But what contributes to the regeneration, mature hepatocytes or presumed hepatic stem cells (HSC), or both remains controversial, and some questions are still open, which include:1) where HSC locate in or come from and whether there exist marrow-derived HSC and small hepatocyte with HSC feature.2) What a role HSC play in liver regeneration. On the one hand, the liver is reported to be able to regenerate completely by proliferation of mature hepatocytes after 2/3 partial hepatectomy (PH); On the other hand, the rat oval cells (OVC) are considered to be adult HSC, which possess bi-potentials diffentiating to hepatocytes and cholangiocytes and which appear around the small bile ducts and the canals of Hering (COH). This is coincident with Zajicet' s concept of streaming liver. But no oval cells have been found in the normal liver; OVC or another kind of small hepatocyte appear only when the division of mature hepatocytes is prohibited by suppressors(e.g.,Retrorsine, RS) in advance and when acute liver injury provokes violent regeneration demand. Furthermore, some researchers believe that OVC orginate from bone marrow cells, but others do not agree. Our research group has successfully set up an experimental model of inducing the development of mouse OVC by RS and PH (RS/PH), and set up an adult intrahepatic HSC candidate lineage (LEPCs) of C57 mouse in vitro. Accidentally, a few oval-cell-like cells in the portal area and a kind of small mitosis in the liver sinus in the PH group were observed in the section review, which invited our attention in that the role of HSC might be deeply understood whereby.3) Some reports have shown that rat or human myelocytes can differentiate/ transdifferentiate into hepatocytes under certain conditions. But whether the reproducible cultured adult intrahepatic HSC from the mouse can preserve the features of HSC after long-term passage, implant in the liver, proliferate/differentiate into hepatocytes and thus support restoration of the injured liver is unknown.The present study attempts to answer these questions. The following is the main methods, results and conclusion of the study.1.Different candidates of HSC of C57 mice: bone marrow cells(BMC), FECFCderived from fetal liver cells and two adult intrahepatic HSC candidates (LEPCs and HECFC) were obtained. The candidates (from BMC, fetal liver or adult liver) manifested the HSC characterastics in the induction experiment in vitro, in the transplantion test forming spleen nodes, and in the detection of Mx-Cre and sry derived from donor BMC in recipients by immune histochemistry (IHC) and PCR. The expression of hepatocyte/bile duct markers increased in colony-forming cells derived from transplanted BMC in spleen nodes following liver injury.2.Pathologic observations on hepatocytes, cholangiocytes, OVC , big mitoses of hepatocytes and small mitoses of potential HSC shown: 1) RS/PH group: the intrahepatic and extrahepatic HSC ' s proliferation reflected by small mitoses may be the key element in the restoration; 2)RS group: the intrahepatic and extrahepatic HSC may be the key element in the turnover of hepatocytes, which was revealed by gradual increase of small mitoses after day 14; 3)Both hepatocytes and HSC may cooperate in the the liver restoration in PH group, which was revealed by increase of both big and small mito...
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