Johnson L B, Aiken J, Mooney D, Schloo B L, Griffith-Cima L, Langer R, Vacanti J P
Department of Surgery, Children's Hospital, Boston, MA.
Cell Transplant. 1994 Jul-Aug;3(4):273-81. doi: 10.1177/096368979400300403.
The small bowel mesentery provides a unique structure of a large vascularized surface area to support hepatocyte transplantation. Cell-seeded polymeric matrices can be juxtaposed in a relatively atraumatic manner between leaves of mesentery such that adequate exchange of nutrients and diffusion of gases can proceed in the interim while neovascularization occurs. Hepatocytes obtained from (RHA) Wistar rats by collagenase perfusion were seeded onto non-woven filamentous sheets of polyglycolic acid 1 x 3 cm in size and 2 mm thickness to a density of 500,000 cells/cm2. Twenty-six recipient Gunn rats (UDP-glucuronyl transferase deficient) underwent laparotomy. Hepatocyte-ladened polymer sheets were placed between leaves of mesentery. Eight sheets were placed per animal and the leaves were approximated, creating a functional implant 1 x 3 x 2 cm. Biopsies between 5-99 days after implantation revealed neovascularization, moderate inflammatory reaction and the presence of viable hepatocytes in 96% (25/26). Immunoperoxidase studies using anti-albumin antibody substantiated hepatocyte specific function in implants. HPLC profiles of bile from Gunn rats transplanted with hepatocytes from congeneic (RHA) rats demonstrated the presence of bilirubin conjugates. There were no conjugation fractions seen in control gunn rats without hepatocyte transplantation. Although total serum bilirubin did not significantly decrease, conjugated bilirubin was identified in 46% (12/26) animals after transplantation with congeneic hepatocytes. We conclude that the mesentery of the small bowel provides a large vascularized surface for cell transplantation. Large numbers of metabolically active hepatocytes can engraft, vascularize, and show function. The mesentery may be a potential bed for clinical hepatocyte transplantation.
小肠系膜提供了一个具有大血管化表面积的独特结构，以支持肝细胞移植。接种细胞的聚合物基质可以以相对无创的方式并列置于肠系膜叶之间，这样在新血管形成期间，营养物质的充分交换和气体扩散可以进行。通过胶原酶灌注从（RHA）Wistar大鼠获得的肝细胞接种到尺寸为1×3 cm、厚度为2 mm的聚乙醇酸非织造丝状片材上，密度为500,000个细胞/cm²。26只受体Gunn大鼠（缺乏尿苷二磷酸葡萄糖醛酸基转移酶）接受了剖腹手术。将负载肝细胞的聚合物片材置于肠系膜叶之间。每只动物放置8片，将肠系膜叶对合，形成一个1×3×2 cm的功能性植入物。植入后5 - 99天的活检显示有新血管形成、中度炎症反应，并且96%（25/26）的植入物中存在存活的肝细胞。使用抗白蛋白抗体的免疫过氧化物酶研究证实了植入物中肝细胞的特异性功能。用同基因（RHA）大鼠的肝细胞移植的Gunn大鼠胆汁的HPLC图谱显示存在胆红素结合物。未进行肝细胞移植的对照Gunn大鼠中未见到结合部分。虽然总血清胆红素没有显著降低，但在移植同基因肝细胞后的46%（12/26）动物中鉴定出了结合胆红素。我们得出结论，小肠系膜为细胞移植提供了一个大的血管化表面。大量代谢活跃的肝细胞可以植入、形成血管并发挥功能。肠系膜可能是临床肝细胞移植的一个潜在床。
