Arnaout W S, Moscioni A D, Felcher A H, Barbour R L, Brown L L, Demetriou A A
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
Am J Surg. 1989 Jan;157(1):89-92. doi: 10.1016/0002-9610(89)90426-1.
The purpose of this study was to determine whether enterocyte transplantation could be used to correct a specific genetic metabolic defect. Bilirubin uridine diphosphoglucuronyl transferase (UDPGT) activity has been demonstrated in normal rat intestinal mucosa. We hypothesized that normal rat enterocyte transplantation may restore the ability of Gunn rats, which lack bilirubin UDPGT, to conjugate bilirubin. Small intestine was resected from normal Wistar rat donors. Enterocytes were harvested and suspended in Dulbecco's modified Eagle's medium with 10 percent fetal calf serum. Isolated enterocytes were attached to collagen-coated dextran microcarriers and transplanted into congeneic Gunn rat recipients. Recipient rats underwent bile duct cannulation after transplantation, and bile was analyzed for bilirubin glucuronides by high-pressure liquid chromatography. Fifty percent of the transplanted rats showed a significant increase in the concentration of bilirubin monoglucuronide and diglucuronide in their bile 4 and 7 days posttransplantation. Recipient rats had well vascularized microcarrier-enterocyte aggregates in the peritoneal cavity. Our method for intraperitoneal transplantation of isolated enterocytes in rats could potentially be used to correct specific enzymatic and metabolic defects.
本研究的目的是确定肠细胞移植是否可用于纠正特定的遗传代谢缺陷。已在正常大鼠肠黏膜中证实存在胆红素尿苷二磷酸葡萄糖醛酸转移酶(UDPGT)活性。我们推测,正常大鼠肠细胞移植可能恢复缺乏胆红素UDPGT的Gunn大鼠结合胆红素的能力。从小鼠Wistar大鼠供体切除小肠。收获肠细胞并悬浮于含10%胎牛血清的杜尔贝科改良伊格尔培养基中。将分离的肠细胞附着于胶原包被的葡聚糖微载体上,并移植到同基因的Gunn大鼠受体中。移植后对受体大鼠进行胆管插管,并通过高压液相色谱法分析胆汁中的胆红素葡萄糖醛酸酯。50%的移植大鼠在移植后4天和7天胆汁中胆红素单葡萄糖醛酸酯和双葡萄糖醛酸酯的浓度显著增加。受体大鼠腹腔内有血管化良好的微载体-肠细胞聚集体。我们在大鼠中进行分离肠细胞腹腔内移植的方法可能可用于纠正特定的酶和代谢缺陷。