Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
J Mater Chem B. 2019 Mar 14;7(10):1773-1781. doi: 10.1039/c8tb02787k. Epub 2019 Jan 16.
Type 1 diabetes mellitus (T1DM) is a form of diabetes that inhibits or halts insulin production in the pancreas. Although various therapeutic options are applied in clinical settings, not all patients are treatable with such methods due to the instability of the T1DM or the unawareness of hypoglycemia. Islet transplantation using a tissue engineering-based approach may mark a clinical significance, but finding ways to increase the function of islets in 3D constructs is a major challenge. In this study, we suggest pancreatic tissue-derived extracellular matrix as a potential candidate to recapitulate the native microenvironment in transplantable 3D pancreatic tissues. Notably, insulin secretion and the maturation of insulin-producing cells derived from human pluripotent stem cells were highly up-regulated when cultured in pdECM bioink. In addition, co-culture with human umbilical vein-derived endothelial cells decreased the central necrosis of islets under 3D culture conditions. Through the convergence of 3D cell printing technology, we validated the possibility of fabricating 3D constructs of a therapeutically applicable transplant size that can potentially be an allogeneic source of islets, such as patient-induced pluripotent stem cell-derived insulin-producing cells.
1 型糖尿病（T1DM）是一种抑制或阻止胰腺产生胰岛素的糖尿病形式。尽管在临床环境中应用了各种治疗选择，但由于 T1DM 的不稳定性或对低血糖的无知，并非所有患者都可以通过这些方法进行治疗。基于组织工程的胰岛移植可能具有重要的临床意义，但寻找方法来提高 3D 构建体中胰岛的功能是一个主要挑战。在这项研究中，我们提出胰腺组织衍生的细胞外基质作为一种潜在的候选物，以再现可移植 3D 胰腺组织中的天然微环境。值得注意的是，当在 pdECM 生物墨水中共培养时，胰岛素分泌和源自人多能干细胞的胰岛素产生细胞的成熟被高度上调。此外，与人脐静脉衍生的内皮细胞共培养可减少 3D 培养条件下胰岛的中央坏死。通过 3D 细胞打印技术的融合，我们验证了制造具有治疗应用可移植大小的 3D 构建体的可能性，这些构建体可能成为胰岛的同种异体来源，例如患者诱导的多能干细胞衍生的胰岛素产生细胞。
