Lupp A, Hessler F, Philipp T, Danz M, Klinger W
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany.
Exp Toxicol Pathol. 1998 Mar;50(1):1-8. doi: 10.1016/S0940-2993(98)80050-X.
Isolated hepatocytes, liver tissue suspensions, or liver tissue cylinders from biopsies were transplanted into the spleens of adult male rats. Donors were syngenic fetuses, syngenic or allogenic adult rats, or autologous material was obtained from the rat's own liver. The outcome of the different transplantation procedures was evaluated at 1 and 6 months after surgery. Additionally the influence of a 30% hepatectomy (HX) on the result of the transplantation was investigated. When fetal material was transplanted, the best results in sequence with respect to the number of viable hepatocytes within the spleens were obtained (1) after transplantation of syngenic fetal liver tissue suspensions, (2) syngenic fetal liver tissue cylinders and (3) syngenic fetal isolated hepatocytes. HX only improved the results with transplantation of syngenic fetal isolated hepatocytes. After transplantation of syngenic fetal liver tissue suspensions and isolated hepatocytes, but not after transplantation of syngenic fetal liver tissue cylinders, the number of hepatocytes was higher at 6 months than at 1 month after surgery. Concerning syngenic adult liver material, only transplantation of isolated hepatocytes lead to a remarkable and increasing number of surviving hepatocytes at both 1 and 6 months after surgery. These results were further improved by HX. With syngenic adult liver, the other transplantation methods yielded no or nearly no viable hepatocytes in the spleens. In comparison to the results after transplantation of syngenic fetal liver tissue suspensions, transplantation of syngenic adult isolated hepatocytes was less efficient, but still yielded more viable hepatocytes than the transplantation of syngenic fetal isolated hepatocytes. After transplantation of autologous liver tissue suspensions, autologous liver tissue cylinders or allogenic adult liver material only few surviving hepatocytes were observed. At 1 month after transplantation of syngenic fetal liver material, syngenic adult isolated hepatocytes or autologous liver tissue cylinders into the spleens 40-80% of the explants consisted of bile ducts independent from the transplantation method. At 6 months after surgery the bile ducts were much less and in some cases no longer visible. After transplantation of autologous liver tissue suspensions or allogenic adult liver material only very few bile ducts were seen, but anyhow in those cases only poor results were obtained. Thus, with respect to transplantation outcome and long-term liver cell survival, intrasplenic transplantation of both syngenic fetal liver tissue suspensions and syngenic adult isolated hepatocytes seem to be the most suitable methods and should be chosen for further investigations on explant morphology and function.
将分离的肝细胞、肝组织悬液或活检获取的肝组织柱体移植到成年雄性大鼠的脾脏中。供体为同基因胎儿、同基因或异基因成年大鼠,或者自体材料取自大鼠自身肝脏。在术后1个月和6个月评估不同移植程序的结果。此外,还研究了30%肝切除术(HX)对移植结果的影响。当移植胎儿材料时,就脾脏内存活肝细胞数量而言,依次获得最佳结果的是:(1)同基因胎儿肝组织悬液移植后,(2)同基因胎儿肝组织柱体移植后,(3)同基因胎儿分离肝细胞移植后。HX仅改善了同基因胎儿分离肝细胞移植的结果。同基因胎儿肝组织悬液和分离肝细胞移植后,而非同基因胎儿肝组织柱体移植后,术后6个月的肝细胞数量高于术后1个月。关于同基因成年肝脏材料,仅分离肝细胞移植导致术后1个月和6个月存活肝细胞数量显著增加且持续上升。HX进一步改善了这些结果。对于同基因成年肝脏,其他移植方法在脾脏中未产生或几乎未产生存活肝细胞。与同基因胎儿肝组织悬液移植后的结果相比,同基因成年分离肝细胞移植效率较低,但仍比同基因胎儿分离肝细胞移植产生更多存活肝细胞。自体肝组织悬液、自体肝组织柱体或异基因成年肝脏材料移植后,仅观察到少数存活肝细胞。在将同基因胎儿肝脏材料、同基因成年分离肝细胞或自体肝组织柱体移植到脾脏后1个月,40 - 80%的外植体由与移植方法无关的胆管组成。术后6个月,胆管数量少得多,在某些情况下不再可见。自体肝组织悬液或异基因成年肝脏材料移植后仅见极少数胆管,但无论如何在这些情况下仅获得较差结果。因此,就移植结果和长期肝细胞存活而言,同基因胎儿肝组织悬液和同基因成年分离肝细胞的脾内移植似乎是最合适的方法,应选择用于进一步研究外植体形态和功能。