Testing of unique 3D-printed pancreatic tissues to confirm appropriate insulin-releasing function for the regulation of blood glucose in diabetes

通过移植分化的干细胞来替代胰岛素是治疗糖尿病的一种很有前途的方法，目前正在**进行临床测试，包括在温哥华。临床测试的初步结果表明，**需要改进以改善移植物的血管形成、存活率和功能。总部位于温哥华的Aspect生物系统有限公司已经开发出细胞生物打印技术，可能能够解决这些限制。因此，**本项目的目标是评估含有分化为胰岛素分泌细胞的人**胚胎干细胞(HESCs)的新型生物打印3D组织的存活和功能。这项工作将在之前由NSERC Engage计划资助的项目的第一阶段**上进行扩展，在该阶段中，我们与AspectTM合作**评估和优化生物打印组织中未分化的hESCs的生存能力。基于我们的进展，我们现在可以**优化3D胰腺组织，以确定哪种成分最能支持分化的hESCs的细胞活性和**功能。生物打印细胞的体外功能将通过在动态灌流装置中测量胰岛素**对营养物质和β细胞促分泌剂的反应而进行评估。进一步的测试将在免疫缺陷的糖尿病大鼠身上进行，以确定生物打印组织是否能够**逆转糖尿病并恢复对血糖调节的控制。基弗实验室将为已经分化为胰岛素产生细胞的人类ES**细胞提供方面的信息。这些细胞将使用Aspect独特的藻酸盐/胶原蛋白生物墨水按Aspect生物打印成**活的生物兼容3D结构。该项目将为处于学术界和产业界交界处的尖端生物医学工程的学生提供一个**绝佳的培训机会，并可能导致对后续研究和开发的大量投资。

Insulin replacement by implant of differentiated stem cells is a promising approach to treat diabetes, and is now**being tested clinically, including here in Vancouver. Initial findings from the clinical testing indicate that**improvements are required to improve graft vascularization, survival and function. Vancouver-based Aspect**Biosystems Ltd has developed cell bioprinting technology that may be able to address these limitations. Thus,**the goal of this project is to assess the survival and function of novel bioprinted 3D tissue containing human**embryonic stem cells (hESCs) differentiated toward insulin-producing cells. This work will expand on the first**phase of the project, previously funded by the NSERC Engage program, in which we collaborated with Aspect**to assess and optimize the viability of undifferentiated hESCs in bioprinted tissue. Based upon our progress, we**can now optimize the 3D pancreas tissue to determine which composition best supports cell viability and**function of differentiated hESCs. In vitro function of bioprinted cells will be assessed by measuring insulin**secretion in response to nutrients and beta cell secretagogues in a dynamic perifusion apparatus. Further testing**will be conducted in immunodeficient, diabetic rats to determine whether the bioprinted tissue is able to**reverse diabetes and restore control of glucose regulation. The Kieffer lab will provide Aspect with human ES**cells that have been differentiated toward insulin-producing cells. These cells will be bioprinted by Aspect into**living biocompatible 3D structures using Aspect's unique alginate/collagen bioink. The project will provide an**excellent training opportunity for students in cutting edge biomedical engineering at the interface of academia**and industry, and could lead to substantial investments in follow-up research and development.