Intrasplenic or Subperitoneal Hepatocyte Transplantation to Increase Survival after Surgically Induced Hepatic Failure?

Abstract

Background: As a basis for future clinical questions, we evaluated the efficacy of hepatocyte transplantation in a surgical model using a subperitoneal or intrasplenic approach for cell implantation. Methods: In rats, acute liver failure was induced by subtotal hepatectomy. Series of allogenic hepatocyte transplantations were performed by varying cell number, site, and sequence of cell transplantation. Results: Following subperitoneal or intrasplenic cell implantation subsequent to liver surgery, no survival benefit was achieved when compared to the control groups. However, intrasplenic cell implantation 24 h prior to liver surgery revealed a statistically significantly higher animal survival (72 vs. 29%). Conclusion: According to our experience, both timing and site of cell implantation played an important role in hepatocyte transplantation. Intrasplenic hepatocyte transplantation 1 day before liver surgery showed the best results in terms of survival. Consequently, we were able to establish a model of hepatocyte transplantation which may be the basis for further investigations evaluating potential treatment modalities to overcome deleterious postoperative liver insufficiency.

NeoHepatocytes From Alcoholics and Controls Express Hepatocyte Markers and Display Reduced Fibrogenic TGF‐β/Smad3 Signaling: Advantage for Cell Transplantation?

“…We have to identify the disease stages at which cell transplantation is effective to replace functional abnormalities of the hepatocytes without interfering with the altered hepatic architecture. There have been several studies testing different application sited for liver cell transplantation in rats and mice (Gabelein et al., 2008; Glanemann et al., 2009; Nagata et al., 2003a,b). Furthermore, we cannot exclude that transplanted NeoHepatocytes become cancerogenic after transplantation.…”

Effect of Liver Cell Transplantation on Acute Hepatic Failure Induced by Massive Liver Resection in the Rat

“… 13 14 Recently, in another similar study, the average survival period after 90% resection was 3 days, and the survival rate 5 days after surgery was lower than 50%. 15 Another recent series showed that in acute liver failure models, 95% liver resection have been reported. 16 However, the mortality rate a short time after surgery was reported to be 80%, and thus this may not be a suitable model for investigating acute liver failure.…”

The possible use of stem cells in regenerative medicine: dream or reality?

“…One explanation may be that the hepatocytes in clinical studies were delivered into the splenic artery and not into the splenic pulp. This view is supported by Nagata and colleagues, who have shown that the route of hepatocyte delivery influences hepatocyte engraftment and function [18,53]. Another open question remains as to whether the human spleen is capable of accommodating a sufficient number of functional hepatocytes to compensate for the cirrhotic liver.…”

“…Tissue engineering After systemic application in animal models of hepatic intoxication and partial hepatectomy, myocardial infarction, nephropathy, cerebral ischemia, lung injury, lung fibrosis, and local irradiation, stem cells are enriched in injured tissue and partially differentiated into tissue-specific cell types [2,[17][18][19][20][21][22][23][24][25][26]. There have also been systemic applications of mesenchymal stem cells in humans with beneficial effect in graft-versus-host disease or osteogenesis imperfecta [27,28].…”

“…Only animals with stable liver cirrhosis 4 weeks after the discontinuation of carbon tetrachloride were subjected to cell therapy. With different cell types applied, namely rat or porcine hepatocytes, syngeneic rat hepatocytes or immortalized rat hepatocytes intrasplenic cell therapy clearly improved liver function and prolonged survival [18,53].…”