Stability and repeat regeneration potential of the engineered liver tissues under the kidney capsule in mice
Stability and repeat regeneration potential of the engineered liver tissues under the kidney capsule in mice
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DOI：
10.3727/000000005783982620
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Nakajima, Y
中科院分区：
文献类型：
--
作者：
Ohashi, K;Kay, MA;Nakajima, Y
利用肝细胞移植的肝组织工程已被提出作为肝移植治疗多种肝脏疾病的替代方案。我们以前曾报道过，通过将成熟的肝细胞移植到细胞外基质中，可以在肝外部位构建具有肝再生潜力的稳定肝组织。本研究旨在评估肝切除诱导再生后肝组织的持久性和重复肝切除诱导再生的潜力。将混合在EHS细胞外基质凝胶中的小鼠分离的肝细胞移植到同基因小鼠的双肾包膜下。肝细胞存活持续超过25周。在一些小鼠中，我们证实了移植的肝细胞在肾包膜下形成了一层薄薄的肝组织，这是由毛细血管之间的索状结构中分化的肝细胞的特定特征决定的。然后，我们评估了外源性肝组织的再生潜力和持久性。为了诱导肝再生，我们在肝细胞移植后70天进行了三分之二肝切除。在该手术后三周，工程化肝组织显示出活跃的再生，达到肝切除术前水平的261 +/- 42%的血清标志物蛋白水平。我们发现再生的肝组织稳定地维持了100天（实验时间）。通过在初次肝切除术后60天进行重复肝切除术（在第70天已经切除了三分之二的肝）来建立重复再生潜力。再次，再生的工程化肝组织显示出活跃的再生，因为血清标志物蛋白水平增加了大约两倍。目前的研究表明，肝组织，这是公认的一部分，宿主幼稚肝脏的再生配置文件，可以在一个异源的网站，没有访问门静脉循环工程。
Liver tissue engineering using hepatocyte transplantation has been proposed as a therapeutic alternative to liver transplantation toward several liver diseases. We have previously reported that stable liver tissue with the potential for liver regeneration can be engineered at extrahepatic sites by transplanting mature hepatocytes into an extracellular matrix. The present study was aimed at assessing the liver tissue persistence after induced regeneration by hepatectomy and repeat regeneration potential induced by repeat hepatectomy. Mouse isolated hepatocytes mixed in EHS extracellular matrix gel were transplanted under both kidney capsules of isogenic mice. The hepatocyte survival persisted for over 25 weeks. In some of the mice, we confirmed that the grafted hepatocytes developed a thin layer of liver tissues under the kidney capsule, determined by specific characteristics of differentiated hepatocytes in cord structures between the capillaries. We then assessed the regenerative potential and persistence of the exogenous liver tissue. To induce liver regeneration, we performed a two-thirds hepatectomy at 70 days after hepatocyte transplantation. Three weeks after this procedure, the engineered liver tissues showed active regeneration, reaching serum marker protein levels of 261 +/- 42% of the prehepatectomy level. We found that the regenerated liver tissue was stably maintained for 100 days (length of the experiment). Repeat regeneration potential was established by performing a repeat hepatectomy (that had been two-thirds hepatectomized at day 70) 60 days after the initial hepatectomy. Again, the regenerated engineered liver tissues showed active regeneration as there was an approximately twofold increase in the serum marker protein levels. The present studies demonstrate that liver tissue, which was recognized as a part of the host naive liver in terms of the regeneration profile, could be engineered at a heterologous site that does not have access to the portal circulation.