Hepatocellular transplantation for experimental ischemic acute liver failure in dogs

Sommer, Bruce G.; Sutherland, David E.R.; Simmons, Richard L.; Najarían, John S.

doi:10.1016/0022-4804(80)90064-5

Cited by 67 publications

(57 citation statements)

References 5 publications

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“…7,8 Theoretically, hepatocyte transplantation would be less invasive and technically less demanding than whole organ transplantation and, if the procedure could be performed percutaneously, recipients would not require prolonged hospitalization. Isolated liver cells can be cryopreserved for emergency use [9][10][11][12] and potentially modified genetically before transplantation to abrogate rejection or enhance function.…”

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confidence: 99%

Hepatocyte transplantation in rats with decompensated cirrhosis

et al. 2000

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Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL 4 ) and animals were studied only when evidence of liver failure did not improve when CCL 4 was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P F .01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P F .01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P F .01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans. (HEPATOLOGY 2000;31: 851-857.)

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confidence: 99%

Hepatocyte transplantation in rats with decompensated cirrhosis

et al. 2000

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“…One of these models (2)(3)(4), that of D-galactosamine (D-GAL) intoxication, has received wide attention because of its reproducible dose/ response relationship, its reversibility and its histologic similarity to that described in human fulminant hepatic failure. Numerous reports in the past years have indicated that, in rats with experimental acute hepatic failure, the administration of various liver fractions is able to significantly improve animal survival by stimulating hepatic regeneration (5)(6)(7)(8)(9)(10)(11).…”

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confidence: 99%

The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D-galactosamine

et al. 1986

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Galactosamine induces a dose-dependent hepatic injury in rats and many other animals. The toxicity of Dgalactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of o-galactosamine-induced hepatic necrosis in rats. o-Galactosamine (2.6 gm per kg of body weight) was administered intraperitoneally to 438 male Lewis strain rats. The·animals were divided into six groups according to the type of treatment: Group 1 (n = 131) saline; Group 2 (n = 40) cytosol (75 mg total protein); Group 3 (n = 75) hepatic stimulatory substance (20 mg total protein); Group 4 (n = 42) 300,000 subfraction (4 mg total protein); Group 5 (n = 68) 300,000 subfraction (2 mg total protein), and Group 6 (n = 82) 50,000 subfraction (0.6 mg total protein). All rats received 4 ml of the test solution intraperitoneally at 48 hr after o-galactosamine administration. The percentage of rats surviving in each group was determined daily for 20 days. Although hepatic stimulatory substance and 50,000 subfraction tended to improve survival in intoxicated rats, only those rats treated with the 300,000

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“…The child was able to stand and walk 6 months after hepatocyte transplantation [87]. [88]. Treatment of liver cirrhosis using different sources of cells has been used by several investigators.…”

Section: Categories Of Patients Selected For Treatment With Fetal Cellsmentioning

confidence: 99%

Cell Based Therapy for Chronic Liver Disease: Role of Fetal Liver Cells in Restoration of the Liver Cell Functions

Tripura¹,

Khan²,

Pande³

2012

Liver Regeneration

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Hepatocellular transplantation for experimental ischemic acute liver failure in dogs

Cited by 67 publications

References 5 publications

Hepatocyte transplantation in rats with decompensated cirrhosis

Hepatocyte transplantation in rats with decompensated cirrhosis

The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D-galactosamine

Cell Based Therapy for Chronic Liver Disease: Role of Fetal Liver Cells in Restoration of the Liver Cell Functions

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