Ambrosino Giovanni, Varotto Sergio, Basso Stefano M M, Cecchetto Attilio, Carraro Paolo, Naso Agostino, De Silvestro Giustina, Plebani Mario, Abatangelo Giovanni, Donato Daniele, Cestrone Andriano, Giron Gianpiero, D'Amico Davide F
Department of Surgical and Gastroenterologic Sciences, Liver Transplant Unit, School of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Cell Transplant. 2003;12(1):43-9. doi: 10.3727/000000003783985124.
A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.
如今,肝移植被认为是治疗许多其他方法难以治愈的肝脏疾病的唯一有效治疗方案。然而,肝移植面临供体短缺的困扰。多年来,人们开发了许多肝脏支持系统来替代肝脏功能,主要作为移植的桥梁。移植分离的肝细胞(HcTx)而非整个肝脏已成为治疗多种疾病最具吸引力的可能性之一。我们在猪急性肝衰竭的手术模型中比较了两种不同的HcTx模型,即微囊化肝细胞(MHcTx)和附着于猪生物基质的肝细胞(PBMHcTx),二者均移植到腹膜内。收集的数据包括生存率、实验室检查结果、血流动力学参数、光学显微镜检查、组织学、MTT和糖原含量。PBMHcTx组的结果优于MHcTx组(p < 0.05)。组织学显示肝细胞形态正常、糖原含量高、活力为75%、MTT呈阳性,且肝细胞与生物基质的黏附率为95%。我们的生物基质(PBM)提供细胞间接触并与细胞外基质相互作用,已证明这在肝细胞存活和基因表达的生理调节中起主要作用,并保证迅速植入和充分的新生血管形成。PBMHcTx是治疗急性肝衰竭的一种有用方法,并且表明在治疗遗传性和获得性疾病方面可能存在肝脏直接基因治疗。