Sabek Omaima M, Farina Marco, Fraga Daniel W, Afshar Solmaz, Ballerini Andrea, Filgueira Carly S, Thekkedath Usha R, Grattoni Alessandro, Gaber A Osama
Department of Surgery, Houston Methodist Hospital, Houston, TX, USA.
Department of Nanomedicine, Institute for Academic Medicine, Houston Methodist Research Institute, Houston, TX, USA; Department of Electronics and Telecommunications, Politecnico di Torino, Torino, Italy.
J Tissue Eng. 2016 Apr 21;7:2041731416638198. doi: 10.1177/2041731416638198. eCollection 2016 Jan-Dec.
Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Pancreas and islet transplants have shown success in re-establishing glucose control and reversing diabetic complications. However, both are limited by donor availability, need for continuous immunosuppression, loss of transplanted tissue due to dispersion, and lack of vascularization. To overcome the limitations of poor islet availability, here, we investigate the potential of bone marrow-derived mesenchymal stem cells differentiated into islet-like insulin-producing aggregates. Islet-like insulin-producing aggregates, characterized by gene expression, are shown to be similar to pancreatic islets and display positive immunostaining for insulin and glucagon. To address the limits of current encapsulation systems, we developed a novel three-dimensional printed, scalable, and potentially refillable polymeric construct (nanogland) to support islet-like insulin-producing aggregates' survival and function in the host body. In vitro studies showed that encapsulated islet-like insulin-producing aggregates maintained viability and function, producing steady levels of insulin for at least 4 weeks. Nanogland-islet-like insulin-producing aggregate technology here investigated as a proof of concept holds potential as an effective and innovative approach for diabetes cell therapy.
糖尿病是世界上最普遍、代价高昂且使人衰弱的疾病之一。胰腺和胰岛移植已成功恢复血糖控制并逆转糖尿病并发症。然而,这两种方法都受到供体可用性、持续免疫抑制需求、移植组织因分散而丢失以及缺乏血管化的限制。为了克服胰岛可用性差的局限性,我们在此研究骨髓来源的间充质干细胞分化为胰岛样胰岛素产生聚集体的潜力。通过基因表达表征的胰岛样胰岛素产生聚集体显示与胰岛相似,并对胰岛素和胰高血糖素呈阳性免疫染色。为了解决当前封装系统的局限性,我们开发了一种新型的三维打印、可扩展且可能可再填充的聚合物构建体(纳米腺体),以支持胰岛样胰岛素产生聚集体在宿主体内的存活和功能。体外研究表明,封装的胰岛样胰岛素产生聚集体保持活力和功能,至少4周内产生稳定水平的胰岛素。这里作为概念验证进行研究的纳米腺体 - 胰岛样胰岛素产生聚集体技术作为糖尿病细胞治疗的有效和创新方法具有潜力。