Functional assessment of proliferating hepatocytes stimulated by hepatic stimulatory substance in ascorbic acid biosynthetic enzyme-deficient rats

Abstract

the possibility of metabolic support by HTx for animals with The functional ability of hepatic stimulatory substance congenital metabolic disorders. 1 We have already reported (HSS)-stimulated proliferating hepatocytes was investigated that transplanted syngeneic hepatocytes survived in the by intrasplenic and/or intraportal transplantation in ascorbic spleen for a long time, recomposing hepatic cord structure, acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats and that they exhibited hepatocellular function by histothat die of osteogenic disorders unless there is AsA supplechemical study.2 However, the time required for transplanted mentation. HSS was extracted from regenerating porcine livhepatocytes to exhibit sufficient hepatocellular function is ers. Hepatocytes isolated from the livers of congeneic ODStoo long for this modality to be used in experimental models /// rats that are capable of synthesizing AsA were of chronic hepatic failure and congenital metabolic disortransplanted into the spleen (Sp-HTx) and/or the portal vein (Pv-HTx) of ODS-od/od rats. The recipients were divided into ders. The ODS-od/od rat is unable to synthesize ascorbic acid sham-operated, HTx(0); group IIa, Sp-HTx; group IIIa, Pv-(AsA) because of a congenital lack of L-gulonolactone oxidase HTx; and group IVa, Sp-and Pv-HTx], HSS-treated groups in the liver and dies of osteogenic disorders following severe [group Ib, HSS only; group IIb, Sp-HTx / HSS; group IIIb, weight loss and bleeding unless they are given exogenous Pv-HTx / HSS; and group IVb, Sp-and Pv-HTx / HSS]. The AsA.3 Congeneic HTx into the spleen and the portal vein recipients were given a diet and water containing AsA for 6 improved the survival rate of ODS-od/od rats when the recipiweeks after HTx, and AsA supplementation was then halted. ent rats were pretreated with a hepatotoxin, 2-acetylThe average bromodeoxyuridine (BrdU) labeling index (LI) aminofluorene, and a subsequent partial hepatectomy (PH) and hepatocyte-occupied ratio in the spleen (H/S ratio) of of 70%. 4 However, this pretreatment and PH cannot be ap-HSS-treated rats were significantly higher than those of HSS-plied in patients with hepatic disorders. Therefore, a method untreated rats. All the rats in HSS-untreated groups and group of inducing immediate and rapid proliferation of transplanted Ib died by 8 weeks after the cessation of AsA. In HSS-treated hepatocytes is urgently needed. groups IIb, IIIb, and IVb, the survival rates were 60%, 50%, Hepatic stimulatory substance (HSS), which can be exand 80%, respectively, at 16 weeks after HTx. The average tracted from fetal, weanling, and regenerating livers, stimuserum AsA level of the surviving rats in groups IIb, IIIb, lates liver regeneration after PH and the proliferation of culand IVb was significantly higher than that in HSS-untreated tured hepatocytes. 5 We have already confirmed the beneficial groups. These results indicate that HSS treatment induced effect of HSS on the survival of intrasplenically transplanted rapid proliferation of tran...

Prolonged Function of Hepatocytes Transplanted into the Spleens of Nagase Analbuminemic Rats

“…Some reports have suggested that HCTx could be developed as an alternative therapy for hepatic failure and congenital metabolic disease in rats and humans. However, it is necessary to develop a noninvasive and practical method for stimulating the proliferation of ectopically transplanted hepatocytes such as some growth factors like hepatocyte-stimulating substrate [24] or hepatocyte growth factor [30]. To evaluate the effect of various methods for improving the function of transplanted hepatocytes, our NARs model may be useful.…”

The Origin of Biliary Ductular Cells that Appear in the Spleen after Transplantation of Hepatocytes

“…Bile duct hyperplasia was induced by BDL followed From Livers of Normal Rats and DAPM-Treated Rats by administration of Furan (23). Seven-week-old rats were first subjected to BDL by double ligating the com-Liver cells were isolated using a collagenase digestion mon bile duct and then resecting the intervening segmethod with a slight modification (2,19). After cannulament.…”

“…we analyzed whether transplantation of nonparencymal cells highly enriched with CK-19-positive biliary cells Adult rat hepatocytes that are transplanted into the resulted in an increased appearance of CK-19-positive spleen of syngeneic rats survive and function over a long cells in the spleen. The second possibility was examined period of time, indicating that transplantation of hepatoby analyzing whether transplantation of hepatocyte fraccytes into the spleen is a therapeutic option for the treattions depleted of precursors of oval cells resulted in dement of acute or chronic liver failure and congenital liver creased formation of CK-19-positive cells in the spleen metabolic disorders (5,12,(17)(18)(19). It has been shown that or, conversely, that of nonparenchymal cell fractions enhepatocyte transplantation into the spleen is accompariched with oval cells caused increased generation of CKnied by an appearance of biliary cells that form ductular 19-positive cells in the spleen.…”