Mesenchymal stem cells support hepatocyte function in engineered liver grafts
Mesenchymal stem cells support hepatocyte function in engineered liver grafts
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DOI：
10.4161/org.27879
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发表时间：
2014-04-01
期刊：
影响因子：
2.3
通讯作者：
Kitagawa, Yuko
中科院分区：
文献类型：
--
作者：
Kadota, Yoshie;Yagi, Hiroshi;Kitagawa, Yuko
最近的研究表明，器官去细胞化是一种很有前途的方法，以促进再生治疗的临床应用，通过提供一个平台，器官工程。这种独特的策略使用天然基质作为功能细胞的储存库，这些细胞在植入体内时可能显示出治疗潜力。人工肝的合适细胞来源已经争论了一段时间。人工肝中所需的细胞类型是原代肝细胞，但除此之外，其他支持细胞可能有助于这种干细胞技术。在这种情况下，使用间充质干细胞（MSC）是一种选择，符合治疗性器官工程的标准。理想情况下，需要支持性细胞来（1）通过增强肝细胞功能来减少工程化肝脏中所需的肝细胞质量，（2）以旁分泌方式或通过直接接触来调节肝再生，以及（3）在储存期间增强实质细胞的可再生性。在这里，我们描述了增强肝功能实现的顺序输注细胞的策略，并说明了共培养骨髓源性间充质干细胞与原代肝细胞在工程全肝支架的优势。将这些由MSC和肝细胞定殖的共再细胞化的肝脏支架移植到活体动物中。建立血流后，我们发现移植物中粘附分子和促血管生成因子的表达上调。
Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology. In this context, the use of mesenchymal stem cells (MSC) is an option meeting the criteria for therapeutic organ engineering. Ideally, supportive cells are required to (1) reduce the hepatic cell mass needed in an engineered liver by enhancing hepatocyte function, (2) modulate hepatic regeneration in a paracrine fashion or by direct contact, and (3) enhance the preservability of parenchymal cells during storage. Here, we describe enhanced hepatic function achieved using a strategy of sequential infusion of cells and illustrate the advantages of co-cultivating bone marrow-derived MSCs with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSCs and hepatocytes were transplanted into live animals. After blood flow was established, we show that expression of adhesion molecules and proangiogenic factors was upregulated in the graft.