Treatment of surgically induced acute liver failure by transplantation of conditionally immortalized hepatocytes.
Treatment of surgically induced acute liver failure by transplantation of conditionally immortalized hepatocytes.
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通过条件永生化肝细胞移植治疗手术引起的急性肝衰竭。
DOI：
10.1097/00007890-199706150-00001
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
Fox,IJ
中科院分区：
文献类型：
--
作者：
Nakamura,J;Okamoto,T;Schumacher,IK;Tabei,I;Chowdhury,NR;Chowdhury,JR;Fox,IJ
由于可用于肝细胞分离的人类肝脏的短缺，限制了其临床应用。克隆的、有条件永生化的肝细胞可以在培养物中生长，但在移植时会失去其转化的表型并提供代谢支持，这将极大地促进急性肝衰竭的治疗。为了实现这一目标，我们使用复制缺陷型重组逆转录病毒转导分离的刘易斯大鼠肝细胞，该病毒能够转移编码不耐热突变型猿猴病毒40 T抗原（SV 40 ts）的基因。克隆的永生化肝细胞在33 ℃下增殖。在非允许温度（37-39 ℃）下，它们停止生长并表现出分化的肝细胞的特征。这些细胞在移植到患有严重联合免疫缺陷病的小鼠或同基因大鼠中时不会产生肿瘤。为了诱导急性肝衰竭，对刘易斯大鼠进行90%肝切除术（Hpx）并给予5%口服葡萄糖。未行肝细胞移植的大鼠均在96 h内死亡，脾内注射10× 10 6个原代刘易斯肝细胞的大鼠死亡率为50（G2，n= 6）或10× 106 SV 40 ts-条件永生化（SV 40 ts-ci）肝细胞（G3，n= 8）肝切除前1天90%存活，而腹腔注射200× 106原代刘易斯大鼠肝细胞的大鼠，G4组（n= 10）和G5组（n= 10）肝细胞存活率分别为200× 106和200× 106。腹腔注射200× 106原代刘易斯大鼠（G7，n= 9）或SV 40 ts-ci肝细胞（G8，n= 10）的细胞匀浆后，Hpx当天的存活率分别为33%和40%，而腹腔注射200× 106刘易斯大鼠骨髓细胞（G6，n= 7）后的存活率为29%。因此，在急性肝功能不全期间，移植的条件永生化肝细胞可以与原代肝细胞一样有效地支持生命。这项工作代表了开发肝细胞系的第一步，该细胞系将部分缓解器官供体短缺，并可能具有潜在的临床价值。
The shortage of human livers available for hepatocyte isolation limits its clinical application. The availability of cloned, conditionally immortalized hepatocytes that could be grown in culture but would lose their transformed phenotype and provide metabolic support upon transplantation would greatly facilitate the treatment of acute liver failure. Toward this goal, we transduced isolated Lewis rat hepatocytes using a replication-defective recombinant retrovirus capable of transferring a gene encoding a thermolabile mutant simian virus 40 T antigen (SV40ts). The cloned, immortalized hepatocytes proliferate at 33 C. At the nonpermissive temperatures (37-39 C), they stop growing and exhibit characteristics of differentiated hepatocytes. These cells did not produce tumors when transplanted in mice with severe combined immunodeficiency disease or in syngeneic rats. To induce acute liver failure, Lewis rats were subjected to 90% hepatectomy (Hpx) and given 5% oral dextrose. All rats that did not undergo hepatocyte transplantation died within 96 hr. Fifty percent of rats that received intrasplenic injection of 10× 10 6 primary Lewis rat hepatocytes (G2, n= 6) or 10× 10 6 SV40ts-conditionally immortalized (SV40ts-ci) hepatocytes (G3, n= 8) 1 day before 90% hepatectomy survived, whereas 80% of rats that received an intraperitoneal injection of 200× 10 6 primary Lewis rat hepatocytes (G4, n= 10) or 200× 10 6 SV40ts-ci hepatocytes (G5, n= 10) on the day of hepatectomy survived. Survival after intraperitoneal injection of a cellular homogenate of 200× 10 6 primary Lewis rat (G7, n= 9) or SV40ts-ci hepatocytes (G8, n= 10) on the day of Hpx was 33% and 40%, respectively, whereas survival after intraperitoneal injection of 200× 10 6 Lewis rat bone marrow cells (G6, n= 7) was 29%. Thus, transplanted, conditionally immortalized hepatocytes can be as effective as primary hepatocytes in supporting life during acute liver insufficiency. This work represents the first step in developing an hepatocyte cell line that would partially alleviate the organ-donor shortage and could be of potential clinical value.
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肝细胞培养物的无细胞上清液可改善化学诱导的急性肝衰竭大鼠的存活率。
影响因子：
2.2
作者：
P. O'neill;D. Baumgartner;W. I. Lewis;B. Zweber;D. Sutherland
通讯作者：
D. Sutherland
肝细胞移植到脾脏后可以增殖吗？
DOI：
--
发表时间：
1987
期刊：
European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes
影响因子：
--
作者：
Bernard Nordlinger;S. R. Wang;M. Bouma;N. Verthier;K. Hillan;R. Delelo;Recaredo Infante
通讯作者：
Recaredo Infante
影响因子：
56.9
作者：
RHIM, JA;SANDGREN, EP;BRINSTER, RL
通讯作者：
BRINSTER, RL
通过紫外线照射的肝细胞移植逆转大鼠肝衰竭。
影响因子：
0.9
作者：
Kawai,Y;Price,JB;Hardy,MA
通讯作者：
Hardy,MA
影响因子：
1.6
作者：
EMOND, J;CAPRONLAUDEREAU, M;HOUSSIN, D
通讯作者：
HOUSSIN, D