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肝实质细胞移植:婴儿和小型儿童安全应用的基础研究。

Liver cell transplantation: basic investigations for safe application in infants and small children.

机构信息

Department of General Pediatrics, University Children's Hospital, 69120 Heidelberg, Germany.

出版信息

Cell Transplant. 2009;18(7):777-86. doi: 10.3727/096368909X470775. Epub 2009 Sep 28.

Abstract

Liver cell transplantation (LCT) is a very promising method for the use in pediatric patients. It is significantly less invasive than whole organ transplantation, but has the potential to cure or at least to substantially improve severe disorders like inborn errors of metabolism or acute liver failure. Prior to a widespread use of the technique in children, some important issues regarding safety and efficacy must be addressed. We developed a mathematical model to estimate total hepatocyte counts in relation to bodyweight to make possible more appropriate dose calculations. Different liver cell suspensions were studied at different flow rates and different catheter sizes to determine mechanical damage of cells by shear forces. At moderate flow rates, no significant loss of viability was observed even at a catheter diameter of 4.2F. Addition of heparin to the cell suspension is favored, which is in contrast to previous animal experiments. Mitochondrial function of the hepatocytes was determined with the WST-1 assay and was not substantially altered by cryopreservation. We conclude that especially with the use of small catheters, human LCT should be safe and efficient even in small infants and neonates.

摘要

肝实质细胞移植(LCT)是一种在儿科患者中非常有前途的治疗方法。与整个器官移植相比,它的侵入性更小,但有可能治愈或至少大大改善代谢性疾病或急性肝衰竭等严重疾病。在该技术在儿童中广泛应用之前,必须解决一些关于安全性和有效性的重要问题。我们开发了一种数学模型,用于根据体重估算总肝细胞计数,以便能够更准确地计算剂量。我们在不同的流速和不同的导管尺寸下研究了不同的肝实质细胞悬液,以确定剪切力对细胞的机械损伤。在中等流速下,即使导管直径为 4.2F,也没有观察到明显的活力丧失。肝素的添加有利于细胞悬液,这与之前的动物实验相反。我们用 WST-1 测定法测定了肝细胞的线粒体功能,冷冻保存并没有显著改变其功能。我们的结论是,特别是使用小导管,即使是在小婴儿和新生儿中,人源 LCT 也应该是安全有效的。

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