Transplantation of Engineered Chimeric Liver With Autologous Hepatocytes and Xenobiotic Scaffold
Transplantation of Engineered Chimeric Liver With Autologous Hepatocytes and Xenobiotic Scaffold
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DOI：
10.1097/sla.0b013e31825c5349
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发表时间：
2013-03-01
影响因子：
9
通讯作者：
Kobayashi, Eiji
中科院分区：
文献类型：
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作者：
Hata, Toshiyuki;Uemoto, Shinji;Kobayashi, Eiji
目的：在猪中产生人肝可能改善用于人肝移植的移植物的严重短缺，并且使肝移植不需要死亡或活体供体。我们通过大鼠肝细胞在小鼠中的再增殖开发了嵌合肝（CL），并成功地将其移植到具有血管重建的大鼠受体中。方法：将荧光素酶转基因或荧光素酶/LacZ双转基因大鼠的肝细胞移植到20 ~ 30日龄的uPA/SCID小鼠体内，建立大鼠源性肝细胞移植模型。用大鼠肝细胞替代小鼠肝细胞后，将CL移植到野生型刘易斯（n = 30）和无白蛋白血症（n = 10）大鼠中，然后使用他克莫司（TAC）加/不加环磷酰胺（CPA）或不加免疫抑制剂进行免疫抑制。在受体大鼠中通过体内生物成像和多普勒超声检查追踪器官活力4至6个月。还在无白蛋白血症大鼠中评价了4个月的大鼠白蛋白生成。此外，组织学分析，包括Ki 67增殖染色进行了一些recipiers.Results：两种免疫抑制方案显着提高移植物存活率和组织学排斥反应的CLs相比，nonimmunosuppressed组。虽然大鼠白蛋白的生产维持在受体移植后4个月，超声检查显示，专利循环移植6个月。Ki 67染色分析也揭示了CLs的再生潜力后，肝切除术的主机本地liver. Conclusions，而免疫反应仍然留在小鼠起源structures.Conclusions：这是第一次报告表明，工程CLs有潜力作为替代移植物，以取代使用移植物从人类供体。
Objective: Generation of human livers in pigs might improve the serious shortage of grafts for human liver transplantation, and enable liver transplantation without the need for deceased or living donors. We developed a chimeric liver (CL) by repopulation of rat hepatocytes in a mouse and successfully transplanted it into a rat recipient with vessel reconstruction. This study was designed to investigate the feasibility of CL for supporting the recipient after auxiliary liver grafting.Methods: Hepatocytes from luciferase transgenic or luciferase/LacZ doubletransgenic rats were transplanted into 20- to 30-day-old urokinase-type plasminogen activator/severe-combined immunodeficiency (uPA/SCID) mice (n = 40) to create CLs with rat-origin hepatocytes. After replacement of mouse hepatocytes with those from rats, the CLs were transplanted into wild-type Lewis (n = 30) and analbuminemia (n = 10) rats, followed by immunosuppression using tacrolimus (TAC) with/without cyclophosphamide (CPA) or no immunosuppression. Organ viability was traced by in vivo bioimaging and Doppler ultrasonography in the recipient rats for 4 to 6 months. Rat albumin production was also evaluated in the analbuminemia rats for 4 months. In addition, histological analyses including Ki67 proliferation staining were performed in some recipients.Results: Both immunosuppressive protocols significantly improved graft survival and histological rejection of CLs as compared to the nonimmunosuppressed group. Although rat albumin production was maintained in the recipients for 4 months after transplantation, ultrasonography revealed patent circulation in the grafts for 6 months. Ki67 staining analysis also revealed the regenerative potential of CLs after a hepatectomy of the host native liver, whereas immune reactions still remained in the mouse-origin structures.Conclusions: This is the first report showing that engineered CLs have potential as alternative grafts to replace the use of grafts from human donors.