Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN 4700, Boston, MA, 02114, USA.
Curr Diab Rep. 2018 Oct 2;18(11):122. doi: 10.1007/s11892-018-1072-7.
Engineering endocrine pancreatic tissue is an emerging topic in type 1 diabetes with the intent to overcome the current limitation of β cell transplantation. During islet isolation, the vascularized structure and surrounding extracellular matrix (ECM) are completely disrupted. Once implanted, islets slowly engraft and mostly are lost for the initial avascular phase. This review discusses the main building blocks required to engineer the endocrine pancreas: (i) islet niche ECM, (ii) islet niche vascular network, and (iii) new available sources of endocrine cells.
Current approaches include the following: tissue engineering of endocrine grafts by seeding of native or synthetic ECM scaffolds with human islets, vascularization of native or synthetic ECM prior to implantation, vascular functionalization of ECM structures to enhance angiogenesis after implantation, generation of engineered animals as human organ donors, and embryonic and pluripotent stem cell-derived endocrine cells that may be encapsulated or genetically engineered to be immunotolerated. Substantial technological improvements have been made to regenerate or engineer endocrine pancreatic tissue; however, significant hurdles remain, and more research is needed to develop a technology to integrate all components of viable endocrine tissue for clinical application.
工程化胰岛组织是 1 型糖尿病领域的一个新兴课题，旨在克服目前胰岛移植的局限性。在胰岛分离过程中，血管化结构和周围细胞外基质（ECM）会被完全破坏。胰岛移植后，胰岛会缓慢植入，但在最初的无血管期大多会丢失。本文讨论了工程化胰岛所需的主要构建模块：（i）胰岛细胞巢 ECM，（ii）胰岛细胞巢血管网络，和（iii）新的内分泌细胞来源。
目前的方法包括以下几种：将人胰岛种植于天然或合成 ECM 支架上进行胰岛组织工程化，在植入前对天然或合成 ECM 进行血管化，在植入后对 ECM 结构进行血管功能化以促进血管生成，生成可作为人类器官供体的工程化动物，以及胚胎和多能干细胞衍生的可被包裹或基因工程改造以实现免疫耐受的内分泌细胞。为了再生或工程化胰岛组织，已经取得了实质性的技术进步；然而，仍存在重大障碍，需要进一步的研究来开发一种技术，将有活力的胰岛组织的所有成分整合起来，用于临床应用。
