Improving islet transplantation: a road map for a widespread application for the cure of persons with type I diabetes

被引:23
作者
Korsgren, Olle [1 ]
Nilsson, Bo [1 ]
机构
[1] Uppsala Univ, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden
关键词
bone marrow; encapsulation; islet transplantation; solid tissues; titanium; Young's modulus; PORCINE ISLETS; ARTIFICIAL PANCREAS; CELL-DIFFERENTIATION; THROMBIN GENERATION; NONHUMAN-PRIMATES; BONE-FORMATION; WHOLE-BLOOD; STEM-CELLS; XENOTRANSPLANTATION; GROWTH;
D O I
10.1097/MOT.0b013e328332c44c
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review The widespread application of replacement therapies for type I diabetes is at present limited by the side-effects of systemic immunosuppression. Results obtained in several animal models show that islet encapsulation can control the rejection process without systemic side-effects. However, results have, in general, been disappointing when transferred to large animal models or to humans. Recent findings Growing insights into how cells respond to mechanical forces and surrounding extracellular matrixes indicate that differences in the Young's modulus (the resistance to deformation) between the implanted biomaterial and surrounding tissues induce inflammation and fibrosis. A valid approach would be to select for implantation a tissue having a higher value of the Young's modulus, for example, bone, allowing direct contact with the highly vascularized bone marrow providing nutrient and oxygen support as well as a rapid distribution of released insulin to the systemic circulation. Summary Development of a biochamber with bone-integrating properties will allow initiation of clinical trials with allogeneic human islets, xenogeneic pig islets or insulin-producing cells generated from human embryonic stem cell (hESC)/inducible pluripotent stem cell (iPSC).
引用
收藏
页码:683 / 687
页数:5
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