Borel-Rinkes I H, Bijma A M, Kappers W A, Sinaasappel M, Hoek F J, Jansen P L, Valerio D, Terpstra O T
Department of Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Transplantation. 1992 Aug;54(2):210-4. doi: 10.1097/00007890-199208000-00004.
This study was undertaken to assess the metabolic effect of fetal and adult hepatocyte transplantation in the Gunn rat, genetically incapable of bilirubin conjugation. A comparison was made between fetal and adult hepatocytes transplanted into the spleen, and those injected into polytetrafluoroethylene (PTFE) solid supports that had previously been implanted intraperitoneally. Between 4 and 12 weeks after intrasplenic transplantation of adult liver cells, serum bilirubin was significantly decreased when compared with control animals (39.6 +/- 5.6%; P less than 0.01 vs. controls). Intrasplenic transplantation of fetal hepatocytes resulted in a maximal decrease of 33.2 +/- 9.1% at 8 weeks postoperatively (P less than 0.02 vs. controls). Similar declines of serum bilirubin levels were found after transplantation of adult or fetal liver cells into the solid supports. At 12 weeks after transplantation, bilirubin conjugates were detectable in the bile of all animals that underwent intrasplenic hepatocyte transplantation and in 60% of those that underwent the solid support procedure, whereas none could be detected in control animals. Histological evidence of surviving cells was obtained in all but one animal at 12 weeks, and confirmed at 12 months postoperatively. It is concluded that the PTFE solid support technique offers an attractive alternative to the intrasplenic route, and that both fetal and adult hepatocytes, transplanted in either way still exert their conjugating activity after 12 weeks.
本研究旨在评估胎儿和成人肝细胞移植对遗传性无法进行胆红素结合的Gunn大鼠的代谢影响。对移植到脾脏的胎儿和成人肝细胞,与注射到先前已植入腹腔的聚四氟乙烯(PTFE)固体支架中的胎儿和成人肝细胞进行了比较。在将成人肝细胞脾内移植后的4至12周内,与对照动物相比,血清胆红素显著降低(39.6±5.6%;与对照组相比,P<0.01)。胎儿肝细胞脾内移植在术后8周时最大降低了33.2±9.1%(与对照组相比,P<0.02)。将成人或胎儿肝细胞移植到固体支架后,血清胆红素水平也出现了类似的下降。移植后12周,在所有接受脾内肝细胞移植的动物胆汁中以及60%接受固体支架植入手术的动物胆汁中可检测到胆红素结合物,而对照动物中未检测到。除一只动物外,所有动物在12周时均获得了存活细胞的组织学证据,并在术后12个月得到证实。结论是,PTFE固体支架技术为脾内途径提供了一种有吸引力的替代方法,并且以任何一种方式移植的胎儿和成人肝细胞在12周后仍能发挥其结合活性。