Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
Cell Transplant. 2010;19(6):807-13. doi: 10.3727/096368910X508924. Epub 2010 Jun 23.
Recent advances in liver tissue engineering have encouraged further investigation into the evaluation of therapeutic benefits based on animal disease models. In the present study, liver tissues were engineered in coagulation factor IX knockout (FIX-KO) mice, a mouse model of hemophilia B, to determine if the tissue engineering approach would provide therapeutic benefits. Primary hepatocytes were isolated from the liver of wild-type mice and suspended in a mixture of culture medium and extracellular matrix components. The hepatocyte suspension was injected into the space under the bilateral kidney capsules of the FIX-KO mice to engineer liver tissues. The plasma FIX activities (FIX:C) of the untreated FIX-KO mice were undetectable at any time point. In contrast, the liver tissue engineered FIX-KO mice achieved 1.5-2.5% of plasma FIX activities (FIX:C) and this elevated FIX:C level persisted throughout the 90 day experimental period. Significant FIX mRNA expression levels were found in the engineered liver tissues at levels similar to the wild-type livers. The present study demonstrates that liver tissue engineering could provide therapeutic benefits in the treatment of hemophilia B.
最近在肝脏组织工程方面的进展鼓励进一步研究基于动物疾病模型的治疗效果评估。在本研究中，在凝血因子 IX 敲除（FIX-KO）小鼠中构建了肝脏组织，这是一种乙型血友病的小鼠模型，以确定组织工程方法是否会提供治疗效果。从野生型小鼠的肝脏中分离原代肝细胞，并悬浮在培养基和细胞外基质成分的混合物中。将肝细胞悬浮液注射到 FIX-KO 小鼠的双侧肾包膜下空间中，以构建肝脏组织。未治疗的 FIX-KO 小鼠的血浆 FIX 活性（FIX:C）在任何时间点均无法检测到。相比之下，工程化的 FIX-KO 小鼠的肝脏组织可达到血浆 FIX 活性（FIX:C）的 1.5-2.5%，并且这种升高的 FIX:C 水平在整个 90 天的实验期间持续存在。在工程化的肝脏组织中发现了显著的 FIX mRNA 表达水平，与野生型肝脏相似。本研究表明，肝脏组织工程可以为乙型血友病的治疗提供治疗效果。
