Analysis of hepatocyte distribution and survival in vascular beds with cells marked by 99mTC or endogenous dipeptidyl peptidase IV activity

Gupta, Sanjeev; Vasa, Srinivasa Rao G.; Rajvanshi, Pankaj; Zuckier, Lionel S.; Palestro, Christopher J.; Bhargava, Kuldeep K.

doi:10.1016/s0963-6897(97)00047-x

Cited by 19 publications

(15 citation statements)

References 22 publications

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“…Studies using radiolabeled hepatocytes established that, after injection into the spleen, transplanted cells entered the liver virtually instantaneously 13,19,20. The cell fraction entering the liver represents up to 60%–90% of the cells injected into the splenic pulp.…”

Section: Evidence For Engraftment Survival and Function Of Transplamentioning

confidence: 99%

Hepatocyte transplantation: new horizons and challenges

Malhi

Gupta

2001

Journal of Hepato-Biliary-Pancreatic Surgery

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Hepatocyte transplantation represents an alternative strategy for treating liver disease. Liver repopulation following acute liver failure could, potentially, eliminate the requirement for orthotopic liver transplantation. Similarly, the ability to repopulate the liver with disease-resistant hepatocytes offers new opportunities for correcting genetic disorders and treating patients with chronic liver disease. Recent advances concerning the fate of transplanted cells in the recipient liver, the efficacy of cell therapy in outstanding animal models of human disease. and the isolation of progenitor liver cells capable of differentiating into mature hepatocytes have renewed optimism in regard to treating people with hepatocyte transplantation. Recruitment of an increasing number of investigators to the field and the success of recent pilot studies indicate that hepatocyte transplantation will become routine clinical practice in the near future.

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Section: Evidence For Engraftment Survival and Function Of Transplamentioning

confidence: 99%

Hepatocyte transplantation: new horizons and challenges

Malhi

Gupta

2001

Journal of Hepato-Biliary-Pancreatic Surgery

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“…In the cases of intraportal or intrasplenic infusion, major complications can occur, such as portal vein thrombosis, portal hypertension and pulmonary embolism [4]. Moreover, feasibility studies outlined that a significant amount of implanted hepatocytes is lost during the first hours after the implantation due to the stringent conditions imposed to the cells by the blood flow [5]. Lastly, use of allogenic hepatocyte transplantation requires, as whole liver transplantation, chronic immunosuppressant treatment to avoid rejection.…”

Section: Introductionmentioning

confidence: 99%

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

et al. 2013

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Recently, interest has focused on hepatocytes’ implantation to provide end stage liver failure patients with a temporary support until spontaneous recovery or a suitable donor becomes available. To avoid cell damage and use of an immunosuppressive treatment, hepatic cells could be implanted after encapsulation in a porous biomaterial of bead or capsule shape. The aim of this study was to compare the production and the physical properties of the beads, together with some hepatic cell functions, resulting from the use of different material combinations for cell microencapsulation: alginate alone or combined with type I collagen with or without poly-L-lysine and alginate coatings. Collagen and poly-L-lysine increased the bead mechanical resistance but lowered the mass transfer kinetics of vitamin B12. Proliferation of encapsulated HepG2/C3A cells was shown to be improved in alginate-collagen beads. Finally, when the beads were subcutaneously implanted in mice, the inflammatory response was reduced in the case of alginate mixed with collagen. This in vitro and in vivo study clearly outlines, based on a systematic comparison, the necessity of compromising between material physical properties (mechanical stability and porosity) and cell behavior (viability, proliferation, functionalities) to define optima hepatic cell microencapsulation conditions before implantation.

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“…1,2 Transplantation of hepatocytes into the hepatic vascular bed rather than into ectopic sites produces superior engraftment, function, and survival of cells. [3][4][5] Previous studies documented that trans-planted hepatocytes can integrate into the host liver parenchyma. [6][7][8] In the presence of chronically sustained hepatocyte losses, e.g., the uPA transgenic mouse, which expresses a hepatocyte-lethal transgene, 9 and the Fah ⌬exon5 mouse, which is a model of hereditary tyrosinemia type 1, 10 transplantation of normal hepatocytes leads to extensive liver repopulation.…”

mentioning

confidence: 99%

“…We used the dipeptidyl peptidase IV (DPPIV)-deficient F344 rat model of hepatocyte transplantation for studying the kinetics of cell entry into liver plates. [5][6][7][8] In this model, transplanted F344 hepatocytes are localized by virtue of DPPIV expression in the bile canalicular domains. We previously devised strategies to colocalize gene expression and conjoint plasma membrane structures in transplanted cells in the host liver.…”

mentioning

confidence: 99%

Entry and Integration of Transplanted Hepatocytes in Rat Liver Plates Occur by Disruption of Hepatic Sinusoidal Endothelium

et al. 1999

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To establish the process by which transplanted cells integrate into the liver parenchyma, we used dipeptidyl peptidase IV-deficient F344 rats as hosts. On intrasplenic injection, transplanted hepatocytes immediately entered liver sinusoids, along with attenuation of portal vein radicles on angiography. However, a large fraction of transplanted cells (Ͼ70%) was rapidly cleared from portal spaces by phagocyte/macrophage responses. On the other hand, transplanted hepatocytes entering the hepatic sinusoids showed superior survival. These cells translocated from sinusoids into liver plates between 16 and 20 hours after transplantation, during which electron microscopy showed disruption of the sinusoidal endothelium. Interestingly, production of vascular endothelial growth factor was observed in hepatocytes before endothelial disruptions. Portal hypertension and angiographic changes resulting from cell transplantation resolved promptly. Integration of transplanted hepatocytes in the liver parenchyma required cell membrane regenesis, with hybrid gap junctions and bile canaliculi forming over 3 to 7 days after cell transplantation. We propose that strategies to deposit cells into distal hepatic sinusoids, to disrupt sinusoidal endothelium for facilitating cell entry into liver plates, and to accelerate cell integrations into liver parenchyma will advance applications of hepatocyte transplantation. (HEPATOLOGY 1999;29:509-519.)

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Analysis of hepatocyte distribution and survival in vascular beds with cells marked by 99mTC or endogenous dipeptidyl peptidase IV activity

Cited by 19 publications

References 22 publications

Hepatocyte transplantation: new horizons and challenges

Hepatocyte transplantation: new horizons and challenges

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

Entry and Integration of Transplanted Hepatocytes in Rat Liver Plates Occur by Disruption of Hepatic Sinusoidal Endothelium

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