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首页> 外文期刊>Polymers for advanced technologies >Polymer-encapsulated engineered adult mesenchymal stem cells secrete exogenously regulated rhBMP-2, and induce osteogenic and angiogenic tissue formation
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Polymer-encapsulated engineered adult mesenchymal stem cells secrete exogenously regulated rhBMP-2, and induce osteogenic and angiogenic tissue formation

机译：聚合物封装的工程间充质干细胞分泌外源调节的rhBMP-2，并诱导成骨和血管生成组织的形成

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We have previously shown that genetically engineered adult mesenchymal stem cells (AMSCs) expressing recombinant human bone morphogenetic protein -2 (rhBMP-2), under tet-regulation, can induce bone formation and regeneration. We showed that these cells induce bone formation via paracrine and autocrine effect of the secreted rhBMP-2 protein. To distinguish between these two effects, and to develop a platform for continuous delivery of rhBMP-2 by engineered cells protected from the immune system, we have used hydrogel polymer (alginate) in order to encapsulate the AMSCs. Mixing of the cells with potassium alginate, followed by sedimentation in Ca{sup}(2+) solution, results in polymerization of the alginate around the cells, forming microcapsules composed of a membrane allowing diffusion of small molecule and proteins. Encapsulated engineered AMSCs were able to survive inside the capsules in vitro and in vivo and secrete rhBMP-2 under tet-regulation. Transplantation of capsules both subcutaneously and into bone defect elicited physiological response manifested in osteogenic tissue composed of bone trabeculae and cartilage. Inside the capsules, engineered AMSCs differentiated to chondrocytes (autocrine effect), but not to osteoblasts. Newly formed bone has developed around the polymeric external layer without any observed intermediate layer of tissue. There was no evidence of immune response in the transplants area. We therefore conclude that engineered AMSCs can be efficiently encapsulated within polymeric alginate microcapsules, maintain viability, differentiate by autocrine effect, secrete rhBMP-2 under exogenous regulation, and induce bone formation by paracrine effect, with no adverse or immune response to the transplanted capsules.
机译：以前我们已经表明，在tet调节下，表达重组人骨形态发生蛋白-2（rhBMP-2）的基因工程成人间充质干细胞（AMSC）可以诱导骨形成和再生。我们表明，这些细胞通过分泌的rhBMP-2蛋白的旁分泌和自分泌作用诱导骨形成。为了区分这两种作用，并开发一个平台以通过受免疫系统保护的工程细胞连续递送rhBMP-2，我们使用了水凝胶聚合物（藻酸盐）来封装AMSC。将细胞与藻酸钾混合，然后在Ca {sup}（2+）溶液中沉淀，导致藻酸在细胞周围聚合，形成由膜组成的微囊，允许小分子和蛋白质扩散。封装的工程化AMSC能够在体内和体外在胶囊中存活，并在tet调节下分泌rhBMP-2。将胶囊皮下和骨缺损移植引起的生理反应在由骨小梁和软骨组成的成骨组织中表现出来。在胶囊内部，经过工程改造的AMSC分化为软骨细胞（自分泌作用），而不分化为成骨细胞。新形成的骨头已经在聚合物外层周围形成，而没有观察到任何组织中间层。没有证据表明移植区域有免疫反应。因此，我们得出的结论是，工程化的AMSC可以有效地封装在聚合物藻酸盐微胶囊中，保持活力，通过自分泌作用进行分化，在外源调节下分泌rhBMP-2，并通过旁分泌作用诱导骨形成，而对移植的胶囊无不良或免疫反应。

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