Innovative encapsulation platform based on pancreatic extracellular matrix achieve substantial insulin delivery

被引:76
作者
Chaimov, D. [1 ]
Baruch, L. [1 ]
Krishtul, S. [1 ]
Meivar-Levy, I. [2 ,3 ]
Ferber, S. [2 ,3 ]
Machluf, M. [1 ]
机构
[1] Technion Israel Inst Technol, Fac Biotechnol & Food Engn, IL-32000 Haifa, Israel
[2] Sheba Med Ctr, Sheba Regenerat Med Stem Cells & Tissue Engn, Tel Hashomer, Israel
[3] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Tel Aviv, Israel
关键词
Extracellular matrix; Cell encapsulation; Insulin-producing cells; Diabetes; MESENCHYMAL STEM-CELLS; PORE-SIZE; IN-VITRO; MICROENCAPSULATED ISLETS; TISSUE; SCAFFOLDS; LIVER; TRANSPLANTATION; MORPHOGENESIS; REGENERATION;
D O I
10.1016/j.jconrel.2016.07.045
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Cell-based therapies for the treatment of diabetes, generally aim to provide long-term glucose regulated-insulin delivery using insulin producing cells. The delivery platform is crucial for the therapeutic outcome as well as for immunoisolation of the entrapped cells. We have developed a novel artificial pancreas encapsulation platform for the treatment of diabetes that is based on solubilized whole porcine pancreatic extracellular matrix (ECM). These unique capsules were used to entrap human liver cells and mesenchymal stem cells that were induced to differentiate into glucose-regulated insulin-producing cells. We demonstrate that the ECM-microcapsule platform provides a natural fibrous 3D niche, supporting cell viability and differentiation, while significantly improving insulin delivery. In vivo, ECM-encapsulated cells were shown to be non-immunogenic, and most importantly, to significantly improve the glycemic control in diabetic mouse preclinical model, thus establishing a proof-of-concept for this new cell-based insulin delivery platform. (C) 2016 Elsevier B. V. All rights reserved.
引用
收藏
页码:91 / 101
页数:11
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