Engineering Liver Tissues Under the Kidney Capsule Site Provides Therapeutic Effects to Hemophilia B Mice
Engineering Liver Tissues Under the Kidney Capsule Site Provides Therapeutic Effects to Hemophilia B Mice
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DOI：
10.3727/096368910x508924
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Okano, Teruo
中科院分区：
文献类型：
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作者：
Ohashi, Kazuo;Tatsumi, Kohei;Okano, Teruo
肝组织工程的最新进展鼓励进一步研究基于动物疾病模型的治疗益处评估。在本研究中，在凝血因子IX敲除（FIX-KO）小鼠（血友病B的小鼠模型）中对肝组织进行工程化，以确定组织工程方法是否会提供治疗益处。从野生型小鼠的肝脏中分离原代肝细胞，并将其悬浮在培养基和细胞外基质组分的混合物中。将肝细胞悬液注射到FIX-KO小鼠的双侧肾包膜下的空间中以工程化肝组织。在任何时间点，未处理的FIX-KO小鼠的血浆FIX活性（FIX：C）均不可检测。相比之下，肝脏组织工程化FIX-KO小鼠达到1.5-2.5%的血浆FIX活性（FIX：C），并且这种升高的FIX：C水平在整个90天实验期间持续存在。在工程化肝组织中发现了显著的FIX mRNA表达水平，其水平与野生型肝相似。目前的研究表明，肝组织工程可以提供治疗血友病B的治疗效益。
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 wildtype livers. The present study demonstrates that liver tissue engineering could provide therapeutic benefits in the treatment of hemophilia B.