The Experts below are selected from a list of 378435 Experts worldwide ranked by ideXlab platform
Hui-ling Chen - One of the best experts on this subject based on the ideXlab platform.
-
Cells responsible for liver mass regeneration in rats with 2-acetylaminofluorene/partial hepatectomy injury
BMC, 2018Co-Authors: Chin-sung Chien, Ya Hui Chen, Hui-ling Chen, Chiu-ping Wang, Wen-cheng Huang, Mei-hwei ChangAbstract:Abstract Background Whether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type—Hepatocytes or oval cells—mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks Hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH. Methods We employed lineage tracing of dipeptidyl peptidase IV (DPPIV, a Hepatocyte canalicular enzyme)-positive Hepatocytes by subjecting rats with DPPIV-chimeric livers to AAF/PH, AAF/PH/AAF (continuous AAF after AAF/PH to nonselectively inhibit regenerating Hepatocytes), or AAF/PH/retrorsine injury (2-dose retrorsine after AAF/PH to specifically and irreversibly block existing Hepatocytes); through these methods, we determined Hepatocyte contribution to liver regeneration. To determine the oval cell contribution to Hepatocyte regeneration, we performed DPPIV(+) oval cell transplantation combined with AAF/PH injury or AAF/PH/retrorsine injury in DPPIV-deficient rats to track the fate of DPPIV(+) oval cells. Results DPPIV-chimeric livers demonstrated typical oval cell activation upon AAF/PH injury. After cessation of AAF, DPPIV(+) Hepatocytes underwent extensive proliferation to regenerate the liver mass, whereas oval cells underwent Hepatocyte differentiation. Upon AAF/PH/AAF injury where Hepatocyte proliferation was inhibited by continuous AAF treatment following AAF/PH, oval cells extensively expanded in an undifferentiated state but did not produce Hepatocytes. By substituting retrorsine for AAF administration following AAF/PH (AAF/PH/retrorsine), oval cells regenerated large-scale Hepatocytes. Conclusions Hepatocyte self-replication provides the majority of Hepatocyte regeneration, with supplementary contribution from oval cells in rats under AAF/PH injury. Oval cells expand and maintain in an undifferentiated state upon continuously nonselective liver injury, whereas they can significantly regenerate Hepatocytes in a noncompetitive environment
-
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...
-
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.
-
Cells responsible for liver mass regeneration in rats with 2-acetylaminofluorene/partial hepatectomy injury
BMC, 2018Co-Authors: Chin-sung Chien, Ya Hui Chen, Hui-ling Chen, Chiu-ping Wang, Wen-cheng Huang, Mei-hwei ChangAbstract:Abstract Background Whether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type—Hepatocytes or oval cells—mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks Hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH. Methods We employed lineage tracing of dipeptidyl peptidase IV (DPPIV, a Hepatocyte canalicular enzyme)-positive Hepatocytes by subjecting rats with DPPIV-chimeric livers to AAF/PH, AAF/PH/AAF (continuous AAF after AAF/PH to nonselectively inhibit regenerating Hepatocytes), or AAF/PH/retrorsine injury (2-dose retrorsine after AAF/PH to specifically and irreversibly block existing Hepatocytes); through these methods, we determined Hepatocyte contribution to liver regeneration. To determine the oval cell contribution to Hepatocyte regeneration, we performed DPPIV(+) oval cell transplantation combined with AAF/PH injury or AAF/PH/retrorsine injury in DPPIV-deficient rats to track the fate of DPPIV(+) oval cells. Results DPPIV-chimeric livers demonstrated typical oval cell activation upon AAF/PH injury. After cessation of AAF, DPPIV(+) Hepatocytes underwent extensive proliferation to regenerate the liver mass, whereas oval cells underwent Hepatocyte differentiation. Upon AAF/PH/AAF injury where Hepatocyte proliferation was inhibited by continuous AAF treatment following AAF/PH, oval cells extensively expanded in an undifferentiated state but did not produce Hepatocytes. By substituting retrorsine for AAF administration following AAF/PH (AAF/PH/retrorsine), oval cells regenerated large-scale Hepatocytes. Conclusions Hepatocyte self-replication provides the majority of Hepatocyte regeneration, with supplementary contribution from oval cells in rats under AAF/PH injury. Oval cells expand and maintain in an undifferentiated state upon continuously nonselective liver injury, whereas they can significantly regenerate Hepatocytes in a noncompetitive environment
-
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...
-
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.
Ming-fu Chang - One of the best experts on this subject based on the ideXlab platform.
-
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...
-
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.
Ya Hui Chen - One of the best experts on this subject based on the ideXlab platform.
-
Cells responsible for liver mass regeneration in rats with 2-acetylaminofluorene/partial hepatectomy injury
BMC, 2018Co-Authors: Chin-sung Chien, Ya Hui Chen, Hui-ling Chen, Chiu-ping Wang, Wen-cheng Huang, Mei-hwei ChangAbstract:Abstract Background Whether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type—Hepatocytes or oval cells—mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks Hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH. Methods We employed lineage tracing of dipeptidyl peptidase IV (DPPIV, a Hepatocyte canalicular enzyme)-positive Hepatocytes by subjecting rats with DPPIV-chimeric livers to AAF/PH, AAF/PH/AAF (continuous AAF after AAF/PH to nonselectively inhibit regenerating Hepatocytes), or AAF/PH/retrorsine injury (2-dose retrorsine after AAF/PH to specifically and irreversibly block existing Hepatocytes); through these methods, we determined Hepatocyte contribution to liver regeneration. To determine the oval cell contribution to Hepatocyte regeneration, we performed DPPIV(+) oval cell transplantation combined with AAF/PH injury or AAF/PH/retrorsine injury in DPPIV-deficient rats to track the fate of DPPIV(+) oval cells. Results DPPIV-chimeric livers demonstrated typical oval cell activation upon AAF/PH injury. After cessation of AAF, DPPIV(+) Hepatocytes underwent extensive proliferation to regenerate the liver mass, whereas oval cells underwent Hepatocyte differentiation. Upon AAF/PH/AAF injury where Hepatocyte proliferation was inhibited by continuous AAF treatment following AAF/PH, oval cells extensively expanded in an undifferentiated state but did not produce Hepatocytes. By substituting retrorsine for AAF administration following AAF/PH (AAF/PH/retrorsine), oval cells regenerated large-scale Hepatocytes. Conclusions Hepatocyte self-replication provides the majority of Hepatocyte regeneration, with supplementary contribution from oval cells in rats under AAF/PH injury. Oval cells expand and maintain in an undifferentiated state upon continuously nonselective liver injury, whereas they can significantly regenerate Hepatocytes in a noncompetitive environment
-
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...
-
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.
Chin-sung Chien - One of the best experts on this subject based on the ideXlab platform.
-
Cells responsible for liver mass regeneration in rats with 2-acetylaminofluorene/partial hepatectomy injury
BMC, 2018Co-Authors: Chin-sung Chien, Ya Hui Chen, Hui-ling Chen, Chiu-ping Wang, Wen-cheng Huang, Mei-hwei ChangAbstract:Abstract Background Whether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type—Hepatocytes or oval cells—mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks Hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH. Methods We employed lineage tracing of dipeptidyl peptidase IV (DPPIV, a Hepatocyte canalicular enzyme)-positive Hepatocytes by subjecting rats with DPPIV-chimeric livers to AAF/PH, AAF/PH/AAF (continuous AAF after AAF/PH to nonselectively inhibit regenerating Hepatocytes), or AAF/PH/retrorsine injury (2-dose retrorsine after AAF/PH to specifically and irreversibly block existing Hepatocytes); through these methods, we determined Hepatocyte contribution to liver regeneration. To determine the oval cell contribution to Hepatocyte regeneration, we performed DPPIV(+) oval cell transplantation combined with AAF/PH injury or AAF/PH/retrorsine injury in DPPIV-deficient rats to track the fate of DPPIV(+) oval cells. Results DPPIV-chimeric livers demonstrated typical oval cell activation upon AAF/PH injury. After cessation of AAF, DPPIV(+) Hepatocytes underwent extensive proliferation to regenerate the liver mass, whereas oval cells underwent Hepatocyte differentiation. Upon AAF/PH/AAF injury where Hepatocyte proliferation was inhibited by continuous AAF treatment following AAF/PH, oval cells extensively expanded in an undifferentiated state but did not produce Hepatocytes. By substituting retrorsine for AAF administration following AAF/PH (AAF/PH/retrorsine), oval cells regenerated large-scale Hepatocytes. Conclusions Hepatocyte self-replication provides the majority of Hepatocyte regeneration, with supplementary contribution from oval cells in rats under AAF/PH injury. Oval cells expand and maintain in an undifferentiated state upon continuously nonselective liver injury, whereas they can significantly regenerate Hepatocytes in a noncompetitive environment
-
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...
-
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.
