Engineering a liver tissue into subcutaneous space

将肝脏组织植入皮下空间

基本信息

批准号：
15390382
负责人：
NAKAJIMA Yoshiyuki
金额：
$ 9.34万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Recent success in clinical hepatocyte transplantation therapy has encouraged further investigation into bioengineering hepatic tissues in vivo. Engineering tissue in the subcutaneous space is an attractive method ; however, hepatocyte survival has been transient due to insufficient vascular network formation. To establish a vascularized cavity, we created two different types of device that gradually release angiogenic factors, microspheres incorporated acidic FGF and bag style device made of polyethylene terephthalate mesh device coated with poly (vinylalcohol) incorporated basic FGF. The efficacy of these two devices to induce vascular network in the subcutaneous space were confirmed in a mouse and rat studies. Ten days after the device insertion, active vascular network were formed. Isolated mouse hepatocytes transplanted into newly vascularized subcutaneous cavities allowed for persistent survival up to 120 days. In the absence of a vascularized compartment, the survival of the transplanted hepatocytes was markedly diminished. Functional maintenance of the engineered hepatic tissues was confirmed by high expression of liver-specific mRNAs and proteins. These engineered hepatic tissues have the ability to take up inoculated compounds and express strong induction of drug-metabolizing enzymes, demonstrating functional relevance as a metabolic tissue. Hepatic tissues could also engineered in a rat experiment dbased on a same approach. In conclusion, we have created a novel technology to engineer functionally active hepatic tissues in the subcutaneous space, which will likely facilitate hepatocyte-based therapies.

临床肝细胞移植疗法的最新成功鼓励进一步研究体内生物工程肝组织。皮下空间中的工程组织是一种有吸引力的方法。但是，由于血管网络的形成不足，肝细胞的存活率已经短暂。为了建立一个血管化的腔，我们创建了两种不同类型的装置，逐渐释放了血管生成因子，微球结合了酸性FGF和由聚乙二醇二甲酸酯网状设备制成的袋装式FGF和袋式装置，该设备涂有聚乙烯基醇（乙烯基醇）掺有碱性FGF。在小鼠和大鼠研究中证实了这两种设备在皮下空间中诱导血管网络的功效。设备插入十天后，形成了主动血管网络。分离的小鼠肝细胞移植到新的血管皮下腔中，可持续生存长达120天。在没有血管化室的情况下，移植的肝细胞的存活显着降低。通过高表达肝脏特异性mRNA和蛋白质证实了工程肝组织的功能维持。这些工程化的肝组织具有接种化合物并表达对药物代谢酶的强烈诱导的能力，表明功能相关性作为代谢组织。肝组织还可以在相同方法的大鼠实验中进行设计。总之，我们创建了一种新型技术，以在皮下空间中设计功能活性的肝组织，这可能会促进基于肝细胞的疗法。