Xenotransplantation of engineered neonatal porcine islet organoids with multi-targeting immune tolerance
作者单位:Chongqing Medical University
会议名称:《第十四届全国免疫学学术大会》
会议日期:2021年
学科分类:1002[医学-临床医学] 100210[医学-外科学(含:普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
关 键 词:Islet xenotransplantation Neonatal porcine islet organoids Immune tolerance Engineering modification
摘 要:Currently,many clinical trials performed xenotransplantation using neonatal porcine islet and demonstrated the efficiency of neonatal porcine islet as transplantable ***,the outcome of neonatal porcine islet transplantation remains *** of function and immune attack are generally regarded as the main obstacles that hinder the process of neonatal porcine transplant in curing type 1 *** strategies that focus on only one factor or one link benefit little,hence we should concentrate on a panoramic treatment strategy for xenotransplantation of neonatal porcine *** recently flourishing organoid engineering technology can induce stem cells or progenitor cells to committedly differentiate into functional islet organoid and even equip islet organoids with certain immune tolerance abilities through engineering modification,which brings a brand-new panoramic treatment strategy to address the challenges confronted by neonatal porcine *** this study,we designed a neonatal porcine islet organoid culture system following natural differentiation path and by mixing with MSCs and stimulation of PDGF,we acquired vascularized neonatal porcine islet organoids in one *** islet organoids we acquired contain β and a cell populations and have a similar insulin-secreting profile to adult porcine islet,which meet the functional requirements in following in vivo ***,mature islet organoids still remain vulnerable to immune attack in recipient’s body after ***,we take advantage of thiolated natural extracellular matrix(thiolated hyaluronic acid,heparin and gelatin) and polyethylene glycol derivatives with reactive thiol groups to form an immune isolating 3 D barrier around islet *** isolating barrier is made by crosslink of the natural extracellular matrix and polyethylene glycol derivatives mentioned above,and the thickness and mesh size of the barrier can be adjusted to all