Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
J Tissue Eng Regen Med. 2010 Feb;4(2):141-8. doi: 10.1002/term.225.
The ability to engineer biologically active cells and tissue matrices with long-term functional maintenance has been a principal focus for investigators in the field of hepatocyte transplantation and liver tissue engineering. The present study was designed to determine the efficacy and temporal persistence of functional engineered liver tissue following transplantation under the kidney capsule of a normal mouse. Hepatocytes were isolated from human alpha-1 antitrypsin (hA1AT) transgenic mouse livers. Hepatocytes were subsequently transplanted under the kidney capsule space in combination with extracellular matrix components (Matrigel) for engineering liver tissues. The primary outcome of interest was to assess the level of engineering liver tissue function over the experimental period, which was 450 days. Long-term survival by the engineered liver tissue was confirmed by measuring the serum level of hA1AT in the recipient mice throughout the experimental period. In addition, administration of chemical compounds at day 450 resulted in the ability of the engineered liver tissue to metabolize exogenously circulating compounds and induce drug-metabolizing enzyme production. Moreover, we were able to document that the engineered tissues could retain their native regenerative potential similar to that of naïve livers. Overall, these results demonstrated that liver tissues could be engineered at a heterologous site while stably maintaining its functionality for nearly the life span of a normal mouse.
将具有长期功能维持能力的生物活性细胞和组织基质工程化一直是肝细胞移植和肝组织工程领域研究人员的主要关注点。本研究旨在确定在正常小鼠肾囊下移植后，具有功能的工程化肝组织的功效和时间持久性。从人α-1 抗胰蛋白酶（hA1AT）转基因小鼠肝脏中分离出肝细胞。随后，将肝细胞与细胞外基质成分（Matrigel）一起移植到肾囊空间中，以构建肝组织。主要观察指标是在实验期间（450 天）评估工程化肝组织的功能水平。通过在整个实验期间测量受体小鼠血清中 hA1AT 的水平来确认工程化肝组织的长期存活。此外，在第 450 天给予化学化合物，结果表明工程化肝组织能够代谢外循环化合物并诱导药物代谢酶的产生。此外，我们能够证明工程化组织能够保持其固有再生潜能，类似于原始肝脏。总的来说，这些结果表明，可以在异源部位构建肝组织，同时在接近正常小鼠寿命的时间内稳定地维持其功能。
