Background/Aims:Chemotherapy is increasingly used prior to resection of colorectal liver metastases,yet few studies have addressed its effect on the viability and function of hepatocytes.This study evaluated the effec...Background/Aims:Chemotherapy is increasingly used prior to resection of colorectal liver metastases,yet few studies have addressed its effect on the viability and function of hepatocytes.This study evaluated the effect of pre-operative chemotherapy on human hepatocytes.Methods:Studies were carried out on isolated hepatocytes from 47 patients undergoing hepatectomy for colorectal metastases.The function of drug metabolising enzymes in hepatocytes was assessed in vitro,as well as hepatocyte integrity and culture longevity.These results were compared between patients undergoing no pre-operative chemotherapy(N = 8) ,5 fluorouracil(5FU) post-bowel resection(N = 20) ,and neo-adjuvant 5FU alone(N= 7) or in a combination with oxaliplatin(N = 12) .Results:Average cell viability at isolation determined by trypan blue dye exclusion was 71% with no significant difference between the no chemotherapy or pre-resection chemotherapy groups.There was no significant difference in LDH leakage and cellular ATP content over a 96-h time course between the patient treatment groups.The function of cytochromes P450(CYP1A2,CYP2A6,CYP2C9,CYP2D6,CYP2E1,CYP3A4) and phase II enzymes(UDP-glucuronosyltrans-ferase and sulphotransferase) was not adversely affected by pre-operative chemotherapy.Conclusions:Pre-resection chemotherapy does not impair the function or culture integrity of hepatocytes isolated at the time of liver resection.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Background/Aims:Chemotherapy is increasingly used prior to resection of colorectal liver metastases,yet few studies have addressed its effect on the viability and function of hepatocytes.This study evaluated the effect of pre-operative chemotherapy on human hepatocytes.Methods:Studies were carried out on isolated hepatocytes from 47 patients undergoing hepatectomy for colorectal metastases.The function of drug metabolising enzymes in hepatocytes was assessed in vitro,as well as hepatocyte integrity and culture longevity.These results were compared between patients undergoing no pre-operative chemotherapy(N = 8) ,5 fluorouracil(5FU) post-bowel resection(N = 20) ,and neo-adjuvant 5FU alone(N= 7) or in a combination with oxaliplatin(N = 12) .Results:Average cell viability at isolation determined by trypan blue dye exclusion was 71% with no significant difference between the no chemotherapy or pre-resection chemotherapy groups.There was no significant difference in LDH leakage and cellular ATP content over a 96-h time course between the patient treatment groups.The function of cytochromes P450(CYP1A2,CYP2A6,CYP2C9,CYP2D6,CYP2E1,CYP3A4) and phase II enzymes(UDP-glucuronosyltrans-ferase and sulphotransferase) was not adversely affected by pre-operative chemotherapy.Conclusions:Pre-resection chemotherapy does not impair the function or culture integrity of hepatocytes isolated at the time of liver resection.
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.
