THE MESENTERY AS A LAMINATED VASCULAR BED FOR HEPATOCYTE TRANSPLANTATION

THE MESENTERY AS A LAMINATED VASCULAR BED FOR HEPATOCYTE TRANSPLANTATION
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DOI:
10.1177/096368979400300403
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发表时间:
1994-07-01
影响因子:
3.3
通讯作者:
VACANTI, JP
VACANTI, JP
中科院分区:
医学4区
文献类型:
--
作者:
JOHNSON, LB;AIKEN, J;VACANTI, JP

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小肠肠系膜提供了一个独特的结构,一个大的血管化的表面积,以支持肝细胞移植。细胞接种的聚合物基质可以以相对无创伤的方式并置在肠系膜的叶之间,使得在发生新血管形成的同时,可以在中间进行足够的营养物交换和气体扩散。将通过胶原酶灌注从(RHA)Wistar大鼠中获得的肝细胞接种到1 x 3 cm大小和2 mm厚的聚乙醇酸非织造丝状片上,密度为500,000个细胞/cm(2)。26只受体古恩大鼠(UDP-葡萄糖醛酸基转移酶缺陷)进行剖腹手术。将肝细胞负载的聚合物片置于肠系膜的叶之间。每只动物放置8片,对合叶片,处理1 x 3 x 2 cm的功能性植入物。植入后5-99天的活检显示新生血管形成、中度炎症反应和96%(25/26)的活肝细胞存在。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的肝细胞特异性功能。移植同种(RHA)大鼠肝细胞的古恩大鼠胆汁的HPLC图谱证明存在胆红素结合物。在未移植肝细胞的对照古恩大鼠中未观察到结合组分。虽然血清总胆红素没有显著降低,但在同种肝细胞移植后,在46%(12/26)的动物中发现了结合胆红素。我们的结论是,肠系膜的小肠提供了一个大的血管化的表面细胞移植。大量代谢活跃的肝细胞可以移植、血管化并显示功能。肠系膜可能是临床肝细胞移植的潜在床。
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 nonwoven filamentous sheets of polyglycolic acid 1 x 3 cm in size and 2 mm thickness to a density of 500,000 cells/cm(2). 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, treating 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.