Kanai N, Hagihara M, Nagamachi Y, Tsuji K
Department of Transplantation Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Cell Transplant. 1999 Jul-Aug;8(4):413-7. doi: 10.1177/096368979900800411.
Xenogeneic cell (fragment) transplantation may be used as an interim therapy until the organ allotransplanation. Immunologic rejection, however, constitutes the major hurdle. To overcome this problem, "xeno" fetal and neonatal liver fragments (FLF, NLF) were encapsulated into separate micropore devices that protect them from immunological attack by the recipient. The FLF or NLF were then transplanted into beagles with hepatic failure to observe their biological effects. In Experiment 1 (n = 5) beagles were injected IV with D-galactosamine (D-gal, 1.0 g/kg) on day 0 and then received FLF grafts (0, 0.3, 0.8, 1.0, 2.0 g/kg). In Experiment 2 (n = 6) beagles received NLF grafts (1.8 g/kg) and on the following day were injected with D-gal (1.0 g/kg). In Experiment 1 only the high dose of xeno-FLF (2.0 g/kg) decreased the elevated ALT (GPT) and T. Bil. levels. Histologic examination showed that some of the hepatocytes of the host liver survived only in the high-dose graft. In Experiment 2, at 36 and 48 h after D-gal injection, the transplanted group had a significantly lower AST (GOT) level than the control. The grafted NLF survived for 14 days, according to histologic examinations. Thus, encapsulated FLF and NLF xenotransplantation can prevent liver dysfunction in a large animal hepatic failure model.
在进行同种异体器官移植之前，异种细胞（碎片）移植可作为一种过渡性治疗方法。然而，免疫排斥是主要障碍。为克服这一问题，将“异种”胎儿和新生儿肝脏碎片（FLF，NLF）封装在单独的微孔装置中，以保护它们免受受体的免疫攻击。然后将FLF或NLF移植到肝功能衰竭的比格犬体内，观察其生物学效应。在实验1（n = 5）中，比格犬在第0天静脉注射D-半乳糖胺（D-gal，1.0 g/kg），然后接受FLF移植（0、0.3、0.8、1.0、2.0 g/kg）。在实验2（n = 6）中，比格犬接受NLF移植（1.8 g/kg），并在第二天注射D-gal（1.0 g/kg）。在实验1中，只有高剂量的异种FLF（2.0 g/kg）降低了升高的ALT（GPT）和总胆红素水平。组织学检查显示，宿主肝脏中的一些肝细胞仅在高剂量移植组中存活。在实验2中，在注射D-gal后36和48小时，移植组的AST（GOT）水平明显低于对照组。根据组织学检查，移植的NLF存活了14天。因此，封装的FLF和NLF异种移植可预防大型动物肝功能衰竭模型中的肝功能障碍。
