Kocken J M, Borel Rinkes I H, Bijma A M, de Roos W K, Bouwman E, Terpstra O T, Sinaasappel M
Department of Pediatrics, University Hospital Rotterdam, The Netherlands.
Transplantation. 1996 Aug 15;62(3):358-64. doi: 10.1097/00007890-199608150-00010.
The aims of this study were (1) to assess portal hemodynamics during intraportal hepatocyte transplantation (HTX) in dogs, (2) to evaluate a new method for the detection of transplanted hepatocytes using 5-bromo-2'-deoxyuridine (BrdU) incorporation, and (3) to determine the metabolic effects of HTX on an inborn error of the purine metabolism in dalmatian dogs. HTX was performed by intraportal infusion of freshly isolated allogeneic beagle hepatocytes. Portal flow and pressure were monitored continuously during HTX. For the detection experiments, beagles received hepatocytes that had been exposed to BrdU during regeneration of the donor liver, induced by partial hepatectomy. For metabolic studies, dalmatian dogs were used as recipients. Repetitive HTX was performed. As judged by the portal hemodynamics, the number of hepatocytes that could be infused safely varied from 5 x 1O(8) to 8 x 1O(8) in beagles, to 1 x 10(9) in dalmatians. Transaminase levels showed a 5- to 6-fold increase (P=0.05) after HTX, but normalized within 3 weeks. BrdU-positive cells were identified in the recipient livers 2 weeks after HTX and 5-10% of the total amount of transplanted hepatocytes was retrieved. A significant (P=0.05) decrease in serum uric acid was demonstrated after repeated HTX in dalmatians. In conclusion, (1) intraportal HTX is feasible, but portal hypertension limits the maximum amount of hepatocytes that can be infused in one HTX; (2) BrdU labeling is an attractive method for the detection of transplanted hepatocytes in the recipient liver; and (3) after two consecutive hepatocyte transplantations, a temporary correction of the purine metabolism was accomplished in the dalmatian dog.
（1）评估犬门静脉内肝细胞移植（HTX）过程中的门静脉血流动力学；（2）评估一种使用5-溴-2'-脱氧尿苷（BrdU）掺入法检测移植肝细胞的新方法；（3）确定HTX对大麦町犬嘌呤代谢先天性缺陷的代谢影响。通过门静脉内输注新鲜分离的同种异体比格犬肝细胞进行HTX。在HTX过程中持续监测门静脉血流和压力。在检测实验中，比格犬接受在供体肝脏再生过程中经部分肝切除诱导而暴露于BrdU的肝细胞。在代谢研究中，使用大麦町犬作为受体。进行了重复HTX。根据门静脉血流动力学判断，比格犬一次安全输注的肝细胞数量为5×10⁸至8×10⁸个，大麦町犬为1×10⁹个。HTX后转氨酶水平升高了5至6倍（P = 0.05），但在3周内恢复正常。HTX后2周在受体肝脏中鉴定出BrdU阳性细胞，回收的移植肝细胞占总量的5%至10%。在大麦町犬重复HTX后，血清尿酸显著降低（P = 0.05）。总之，（1）门静脉内HTX是可行的，但门静脉高压限制了一次HTX中可输注的最大肝细胞数量；（2）BrdU标记是检测受体肝脏中移植肝细胞的一种有吸引力的方法；（3）连续两次肝细胞移植后，大麦町犬的嘌呤代谢得到了暂时纠正。
