The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Hui-ling Chen - One of the best experts on this subject based on the ideXlab platform.
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Hepatocyte Transplantation and the Differentiation Fate of Host Oval Cells in Acute Severe Hepatic Injury
Cell Transplantation, 2009Co-Authors: Chun-hsien Yu, Chin-sung Chien, Ming-fu Chang, Ya Hui Chen, Mei-hwei Chang, Hui-ling ChenAbstract:Oval cells and Hepatocytes rarely proliferate simultaneously. This study aimed to determine the impacts of hepatocyte transplantation on the response and fate of oval cells that are activated to proliferate in acute severe hepatic injury. Retrorsine + D-galactosamine (R+D-gal) treatment was used to induce acute hepatic injury and to elicit extensive activation of oval cells in male dipeptidyl peptidase IV-deficient F344 rats. These rats were then randomized to receive wild-type hepatocyte transplantation or vehicle intraportally. The kinetics of oval cell response and their differentiation fate were analyzed. Results showed that oval cells were activated early and differentiated into Hepatocytes in R+D-gal-treated rats without hepatocyte transplantation. With hepatocyte transplantation, the oval cells were recruited later and continued to proliferate in parallel with the massive proliferation of transplanted Hepatocytes. They formed ductules and differentiated into biliary cells. When Hepatocytes were tra...
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Impaired hepatocyte regeneration in acute severe hepatic injury enhances effective repopulation by transplanted Hepatocytes.
Cell transplantation, 2009Co-Authors: Hui-ling Chen, Chin-sung Chien, Ming-fu Chang, Ya Hui Chen, Mei-hwei ChangAbstract:Efficient repopulation by transplanted Hepatocytes in the severely injured liver is essential for their clinical application in the treatment of acute hepatic failure. We studied here whether and how the transplanted Hepatocytes are able to efficiently repopulate the toxin-induced acute injured liver. Male dipeptidyl peptidase IV-deficient F344 rats were randomized to receive retrorsine plus D-galactosamine (R+D-gal) treatment or D-galactosamine-alone (D-gal) to induce acute hepatic injury, and retrorsine-alone. In these models, retrorsine was used to inhibit the proliferation of endogenous Hepatocytes while D-galactosamine induced acute hepatocyte damage. Wild-type Hepatocytes (1 x 10(7)/ml) were transplanted intraportally 24 h after D-galactosamine or saline injection. The kinetics of proliferation and repopulation of transplanted cells and the kinetics of cytokine response, hepatic stellate cell (HSC) activation, and matrix metalloproteinase (MMP2) expression were analyzed. We observed that early entry of transplanted Hepatocytes into the hepatic plates and massive repopulation of the liver by transplanted Hepatocytes occurred in acute hepatic injury induced by R+D-gal treatment but not by D-gal-alone or retrorsine-alone. The expressions of transforming growth factor-alpha and hepatocyte growth factor genes in the R+D-gal injured liver were significantly upregulated and prolonged up to 4 weeks after hepatocyte transplantation. The expression kinetics were parallel with the efficient proliferation and repopulation of transplanted Hepatocytes. HSC was activated rapidly, markedly, and prolongedly up to 4 weeks after hepatocyte transplantation, when the expression of HGF gene and repopulation of transplanted Hepatocytes were reduced afterward. Furthermore, the expression kinetics of MMP2 and its specific distribution in the host areas surrounding the expanding clusters of transplanted Hepatocytes are consistent with those of activated HSC. Impaired hepatocyte regeneration after acute severe hepatic injury may initiate serial compensatory repair mechanisms that facilitate the extensive repopulation by transplanted Hepatocytes that enter early the hepatic plates.
Mei-hwei Chang - One of the best experts on this subject based on the ideXlab platform.
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Hepatocyte Transplantation and the Differentiation Fate of Host Oval Cells in Acute Severe Hepatic Injury
Cell Transplantation, 2009Co-Authors: Chun-hsien Yu, Chin-sung Chien, Ming-fu Chang, Ya Hui Chen, Mei-hwei Chang, Hui-ling ChenAbstract:Oval cells and Hepatocytes rarely proliferate simultaneously. This study aimed to determine the impacts of hepatocyte transplantation on the response and fate of oval cells that are activated to proliferate in acute severe hepatic injury. Retrorsine + D-galactosamine (R+D-gal) treatment was used to induce acute hepatic injury and to elicit extensive activation of oval cells in male dipeptidyl peptidase IV-deficient F344 rats. These rats were then randomized to receive wild-type hepatocyte transplantation or vehicle intraportally. The kinetics of oval cell response and their differentiation fate were analyzed. Results showed that oval cells were activated early and differentiated into Hepatocytes in R+D-gal-treated rats without hepatocyte transplantation. With hepatocyte transplantation, the oval cells were recruited later and continued to proliferate in parallel with the massive proliferation of transplanted Hepatocytes. They formed ductules and differentiated into biliary cells. When Hepatocytes were tra...
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Impaired hepatocyte regeneration in acute severe hepatic injury enhances effective repopulation by transplanted Hepatocytes.
Cell transplantation, 2009Co-Authors: Hui-ling Chen, Chin-sung Chien, Ming-fu Chang, Ya Hui Chen, Mei-hwei ChangAbstract:Efficient repopulation by transplanted Hepatocytes in the severely injured liver is essential for their clinical application in the treatment of acute hepatic failure. We studied here whether and how the transplanted Hepatocytes are able to efficiently repopulate the toxin-induced acute injured liver. Male dipeptidyl peptidase IV-deficient F344 rats were randomized to receive retrorsine plus D-galactosamine (R+D-gal) treatment or D-galactosamine-alone (D-gal) to induce acute hepatic injury, and retrorsine-alone. In these models, retrorsine was used to inhibit the proliferation of endogenous Hepatocytes while D-galactosamine induced acute hepatocyte damage. Wild-type Hepatocytes (1 x 10(7)/ml) were transplanted intraportally 24 h after D-galactosamine or saline injection. The kinetics of proliferation and repopulation of transplanted cells and the kinetics of cytokine response, hepatic stellate cell (HSC) activation, and matrix metalloproteinase (MMP2) expression were analyzed. We observed that early entry of transplanted Hepatocytes into the hepatic plates and massive repopulation of the liver by transplanted Hepatocytes occurred in acute hepatic injury induced by R+D-gal treatment but not by D-gal-alone or retrorsine-alone. The expressions of transforming growth factor-alpha and hepatocyte growth factor genes in the R+D-gal injured liver were significantly upregulated and prolonged up to 4 weeks after hepatocyte transplantation. The expression kinetics were parallel with the efficient proliferation and repopulation of transplanted Hepatocytes. HSC was activated rapidly, markedly, and prolongedly up to 4 weeks after hepatocyte transplantation, when the expression of HGF gene and repopulation of transplanted Hepatocytes were reduced afterward. Furthermore, the expression kinetics of MMP2 and its specific distribution in the host areas surrounding the expanding clusters of transplanted Hepatocytes are consistent with those of activated HSC. Impaired hepatocyte regeneration after acute severe hepatic injury may initiate serial compensatory repair mechanisms that facilitate the extensive repopulation by transplanted Hepatocytes that enter early the hepatic plates.
S. Kasai - One of the best experts on this subject based on the ideXlab platform.
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Effects of Bone Marrow and Hepatocyte Transplantation on Liver Injury
Journal of Surgical Research, 2009Co-Authors: Biao Zhang, Mitsuhiro Inagaki, Bojian Jiang, Jun Arikura, Katsuhiro Ogawa, Masaaki Miyakoshi, S. KasaiAbstract:Background The therapeutic effects of bone marrow and hepatocyte transplantation were investigated regarding the treatment of retrorsine-partial hepatectomy-induced liver injury. Methods Analbuminemic F344alb rats were given two doses of retrorsine 2 wk apart, followed 4 wk later by transplantation with F344 rat bone marrow cells or Hepatocytes immediately after a two-thirds hepatectomy. The survival rate, liver regeneration rate, liver functions, albumin-positive Hepatocytes, and normal albumin gene sequences in the liver and serum albumin levels were investigated in the recipients. Results Although 65% retrorsine/partial hepatectomy-treated F344alb died between 1 and 11 d after the partial hepatectomy, only 27.5% of the animals died following bone marrow transplantation, and 50% with hepatocyte transplantation. Both bone marrow and hepatocyte transplantation ameliorated acute liver injury after a partial hepatectomy. Bone marrow transplantation yielded a very small increase in the number of albumin-positive Hepatocytes in the liver, while hepatocyte transplantation resulted in massive replacement of the liver tissues by the donor Hepatocytes associated with an elevation of serum albumin after an extended time. Conclusions Both bone marrow and hepatocyte transplantation could prevent acute hepatic injury, conceivably due to a paracrine mechanism.
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Allogeneic hepatocyte transplantation: contribution of Fas-Fas ligand interaction to allogeneic hepatocyte rejection.
Journal of Gastroenterology and Hepatology, 1998Co-Authors: Toshiyasu Kawahara, Masayuki Sawa, Shunji Futagawa, Kazuya Katô, S. Kasai, Hideo Yagita, Ko Okumura, Michio MitoAbstract:Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted Hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic Hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the rejection of transplanted Hepatocytes, induction of donor-specific unresponsiveness to graft without compromising the host immune system would be ideal.We previously reported that the Fas-Fas ligand system plays a critical role in the CD28-independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti-CD80/86 monoclonal antibodies and anti-FasL monoclonal antibody may prolong the survival of transplanted allogeneic Hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic Hepatocytes and this may lead to the development of a functioning liver substitute.
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Hepatocyte transplantation
[Hokkaido igaku zasshi] The Hokkaido journal of medical science, 1995Co-Authors: S. KasaiAbstract:Hepatocyte transplantation has been studied to treat patients with liver disorders which do not need total replacement of the liver. We found that intrasplenically transplanted Hepatocytes recomposed liver tissues in the spleens of rats and that they revealed similar structure and function of the liver. We also successfully transplanted Hepatocytes into the spleens of rats which were isolated from cirrhotic livers or were thawed after long term cryopreservation. We developed the method to isolate human Hepatocytes from resected liver tissues and made clinical trials of intrasplenic hepatocyte transplantation for the patients with chronic liver disorders. We detected the survival of transplanted Hepatocytes in the spleens of patients, however, further proliferation of them has not yet identified. Hepatocyte transplantation still has many unresolved problems before its clinical application, such as a method to stimulate the proliferation of transplanted Hepatocytes enough to make functional support of the damaged livers. In this article, I will review the present status and future aspects of hepatocyte transplantation.
Anne Weber - One of the best experts on this subject based on the ideXlab platform.
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Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates.
Hepatology, 2008Co-Authors: Ibrahim Dagher, Danièle Pariente, Dominique Franco, Tuan Nguyen, Marie-thérèse Groyer-picard, Panagiotis Lainas, Sylvie Mainot, Catherine Guettier, Anne WeberAbstract:The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as Hepatocytes, and portal vein occlusion increases hepatocyte engraftment. We investigated whether reversible portal vein embolization combined with ex vivo lentivirus-mediated gene transfer is an effective approach for successful hepatocyte engraftment in nonhuman primates and whether the transgene remains expressed in the long term in transplanted Hepatocytes in situ. Simian Hepatocytes were isolated after left lobe resection, and the left and right anterior portal branches of animals were embolized with absorbable material. Isolated Hepatocytes were labeled with Hoechst dye or transduced in suspension with lentiviruses expressing green fluorescent protein under the control of the human apolipoprotein A-II promoter and transplanted via the inferior mesenteric vein. The whole procedure was well tolerated. The embolized liver was revascularized within 2 weeks. The volume of nonembolized liver increased from 38.7% +/- 0.8% before embolization to 55.9% +/- 1% after embolization and Hepatocytes significantly proliferated (10.5% +/- 0.4% on day 3 after embolization). Liver repopulation after transplantation with Hoechst-labeled Hepatocytes was 7.4% +/- 1.2%. Liver repopulation was 2.1% +/- 0.2% with transduced Hepatocytes, a proportion similar to that obtained with Hoechst-labeled cells, given that the mean transduction efficacy of simian hepatocyte population was 34%. Transgene expression persisted at 16 weeks after transplantation. Conclusion: We have developed a new approach to improve hepatocyte engraftment and to express a transgene in the long term in nonhuman primates. This strategy could be suitable for clinical applications. (HEPATOLOGY 2009.).
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Efficient hepatocyte engraftment in a nonhuman primate model after partial portal vein embolization.
Transplantation, 2006Co-Authors: Ibrahim Dagher, Lyes Boudechiche, Julie Branger, Aurore Coulomb-lhermine, Alexandre Parouchev, Michelle Hadchouel, Danièle Pariente, Marion Andreoletti, Dominique Franco, Anne WeberAbstract:BACKGROUND: Hepatocyte transplantation could be an alternative to whole liver transplantation for the treatment of metabolic liver diseases. However, the results of clinical investigations suggest that the number of engrafted Hepatocytes was insufficient to correct metabolic disorders. This may partly result from a lack of proliferation of transplanted Hepatocytes. In rodents, portal ligation enhances hepatocyte engraftment after transplantation. We investigated the effects of partial portal ligation and embolization on engraftment and proliferation of transplanted Hepatocytes in primates. METHODS: Hepatocyte autotransplantation was performed in Macaca monkeys. The left lateral lobe was resected for hepatocyte isolation. The first group of monkeys underwent surgical ligation of the left and right anterior portal branches; in the second group, the same portal territories were obstructed by embolization with biological glue. To evaluate the proportion of cell engraftment Hepatocytes were Hoechst-labeled and transplanted via the portal vein. Cell proliferation was measured by BrdU incorporation. RESULTS: Hepatocyte proliferation was induced by both procedures but it was significantly higher after partial portal embolization (23.5% and 11.2% of dividing Hepatocytes on days 3 and 7) than after ligation (3% and 0.8%). Hepatocytes engrafted more efficiently after embolization than after ligation. They proliferated and participated to liver regeneration representing 10% of the liver mass on day seven and their number remained constant on day 15. CONCLUSIONS: These data suggest that partial portal embolization of the recipient liver improves engraftment of transplanted Hepatocytes in a primate preclinical model providing a new strategy for hepatocyte transplantation.
James M. Hammel - One of the best experts on this subject based on the ideXlab platform.
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hepatocyte transplantation in rats with decompensated cirrhosis
Hepatology, 2000Co-Authors: Naoya Kobayashi, Junta Nakamura, James M. HammelAbstract: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 <.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 <.01). More importantly, survival was prolonged after a single infusion of Hepatocytes and a second infusion prolonged survival from 15 to 128 days (P <.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.
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Hepatocyte transplantation in rats with decompensated cirrhosis.
Hepatology, 2000Co-Authors: Naoya Kobayashi, Junta Nakamura, James M. HammelAbstract: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
