AIM:Acute hepatitis may seldom have a fulminant course. In the treatment of this medical emergency,potential liver support measure must provide immediate and sufficient assistance to the hepatic function.The goal of o...AIM:Acute hepatitis may seldom have a fulminant course. In the treatment of this medical emergency,potential liver support measure must provide immediate and sufficient assistance to the hepatic function.The goal of our study was to study the adequacy of hepatocyte transplantation (HCTx)in two different anatomical sites,splenic parenchyma and peritoneal cavity,in a rat model of reversible acute hepatitis induced by carbon tetrachloride(CCl_4). METHODS:After CCl_4 intoxication,84 male Wistar rats used as recipients were divided in to four experimental groups accordingly to their treatment:Group A(n=-24):intrasplenic transplantation of 10×10~6 isolated hepatocytes,Group B(n=24): intraperitoneal transplantation of 20×10~6 isolated hepatocytes attached on plastic microcarriers,Group C(n=-18):intrasplenic injection of 1 mL normal saline(sham-operated controls), Group D(n=-18):intraperitoneal injection of 2.5 mL normal saline(sham-operated controls).Survival,liver function tests (LFT)and histology were studied in all four groups,on d 2, 5 and 10 post-HCTx. RESULTS:The ten-day survival(and mean survival)in the 4 groups was 72.2%(8.1±3.1),33.3%(5.4±3.4),0% (3.1±1.3)and 33.3%(5.4±3.6)in groups A,B,C,D, respectively(P_(AB0<0.05,P_(AC)<0.05,P_(BD)=NS).In the final survivors,LFT(except alkaline phosphatase)and hepatic histology returned to normal,independently of their previous therapy.Viable hepatocytes were identified within splenic parenchyma(in group A on d 2)and both in the native liver and the fatty tissue of abdominal wall(in group B on d 5). CONCLUSION:A significantly better survival of the intrasplenically transplanted animals has been demonstrated. Intraperitoneal hepatocytes failed to promptly engraft.A different timing between liver injury and intraperitoneal HCTx may give better results and merits further investigation.展开更多
目的观察大鼠肝细胞、转基因肝星状细胞株HGF/CFSC和/或大鼠骨髓来源Thy-1+β2M-细胞(BDTC)共微囊化对肝细胞生物学活性的支持,及腹腔移植混合细胞微囊对急性肝衰竭大鼠肝功能的改善作用.方法利用微囊发生器制备含肝细胞或混合细胞的微...目的观察大鼠肝细胞、转基因肝星状细胞株HGF/CFSC和/或大鼠骨髓来源Thy-1+β2M-细胞(BDTC)共微囊化对肝细胞生物学活性的支持,及腹腔移植混合细胞微囊对急性肝衰竭大鼠肝功能的改善作用.方法利用微囊发生器制备含肝细胞或混合细胞的微囊,依微囊内包裹细胞种类不同,分为微囊化肝细胞组、微囊化肝细胞+CFSC/HGF组)和微囊化肝细胞+CFSC/HGF+BDTC组,通过观察囊内细胞形态和体外培养测定培养液中白蛋白和尿素的分泌,判断各组囊内肝细胞活性和功能的维持;将90%肝大部切除所致的急性肝衰竭大鼠按照移植微囊种类不同分为空囊对照组和上述3个实验组(每组10只),观察腹腔植入后不同时间大鼠的一般状况、存活时间、血生化改变、肝组织再生及微囊化移植物的组织学特征.结果与单独肝细胞微囊者相比,混合细胞微囊内肝细胞存活时间超过1倍,培养液中白蛋白分泌和尿素合成量明显增加(均P<0.01);与对照组相比,微囊化肝细胞或微囊化混合肝细胞移植后,急性肝衰竭大鼠的肝功能显著改善、存活率明显提高(10/10 vs 1/10),其肝组织再生完全;移植21～42 d时,部分微囊附着于肝脏表面并出现血管化,微囊表面存在不同程度的纤维化,微囊内仍有存活的细胞,以微囊化混合肝细胞组优于微囊化肝细胞组.结论混合细胞共微囊化能明显改善囊内肝细胞的存活寿命、形态和功能的维持,微囊化混合肝细胞腹腔移植对促进急性肝衰竭大鼠的肝功能恢复具有显著作用.展开更多
文摘AIM:Acute hepatitis may seldom have a fulminant course. In the treatment of this medical emergency,potential liver support measure must provide immediate and sufficient assistance to the hepatic function.The goal of our study was to study the adequacy of hepatocyte transplantation (HCTx)in two different anatomical sites,splenic parenchyma and peritoneal cavity,in a rat model of reversible acute hepatitis induced by carbon tetrachloride(CCl_4). METHODS:After CCl_4 intoxication,84 male Wistar rats used as recipients were divided in to four experimental groups accordingly to their treatment:Group A(n=-24):intrasplenic transplantation of 10×10~6 isolated hepatocytes,Group B(n=24): intraperitoneal transplantation of 20×10~6 isolated hepatocytes attached on plastic microcarriers,Group C(n=-18):intrasplenic injection of 1 mL normal saline(sham-operated controls), Group D(n=-18):intraperitoneal injection of 2.5 mL normal saline(sham-operated controls).Survival,liver function tests (LFT)and histology were studied in all four groups,on d 2, 5 and 10 post-HCTx. RESULTS:The ten-day survival(and mean survival)in the 4 groups was 72.2%(8.1±3.1),33.3%(5.4±3.4),0% (3.1±1.3)and 33.3%(5.4±3.6)in groups A,B,C,D, respectively(P_(AB0<0.05,P_(AC)<0.05,P_(BD)=NS).In the final survivors,LFT(except alkaline phosphatase)and hepatic histology returned to normal,independently of their previous therapy.Viable hepatocytes were identified within splenic parenchyma(in group A on d 2)and both in the native liver and the fatty tissue of abdominal wall(in group B on d 5). CONCLUSION:A significantly better survival of the intrasplenically transplanted animals has been demonstrated. Intraperitoneal hepatocytes failed to promptly engraft.A different timing between liver injury and intraperitoneal HCTx may give better results and merits further investigation.
文摘目的观察大鼠肝细胞、转基因肝星状细胞株HGF/CFSC和/或大鼠骨髓来源Thy-1+β2M-细胞(BDTC)共微囊化对肝细胞生物学活性的支持,及腹腔移植混合细胞微囊对急性肝衰竭大鼠肝功能的改善作用.方法利用微囊发生器制备含肝细胞或混合细胞的微囊,依微囊内包裹细胞种类不同,分为微囊化肝细胞组、微囊化肝细胞+CFSC/HGF组)和微囊化肝细胞+CFSC/HGF+BDTC组,通过观察囊内细胞形态和体外培养测定培养液中白蛋白和尿素的分泌,判断各组囊内肝细胞活性和功能的维持;将90%肝大部切除所致的急性肝衰竭大鼠按照移植微囊种类不同分为空囊对照组和上述3个实验组(每组10只),观察腹腔植入后不同时间大鼠的一般状况、存活时间、血生化改变、肝组织再生及微囊化移植物的组织学特征.结果与单独肝细胞微囊者相比,混合细胞微囊内肝细胞存活时间超过1倍,培养液中白蛋白分泌和尿素合成量明显增加(均P<0.01);与对照组相比,微囊化肝细胞或微囊化混合肝细胞移植后,急性肝衰竭大鼠的肝功能显著改善、存活率明显提高(10/10 vs 1/10),其肝组织再生完全;移植21～42 d时,部分微囊附着于肝脏表面并出现血管化,微囊表面存在不同程度的纤维化,微囊内仍有存活的细胞,以微囊化混合肝细胞组优于微囊化肝细胞组.结论混合细胞共微囊化能明显改善囊内肝细胞的存活寿命、形态和功能的维持,微囊化混合肝细胞腹腔移植对促进急性肝衰竭大鼠的肝功能恢复具有显著作用.
