title: Innovative encapsulation platform based on pancreatic extracellular matrix achieve substantial insulin delivery.
abstract: 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.
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Chaimov
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Baruch
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Krishtul
authors.affiliation: Sheba Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel; Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Meivar-Levy
authors.affiliation: Sheba Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel; Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Ferber
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel. Electronic address: machlufm@tx.technion.ac.il.
authors.forename: M
authors.initials: M
authors.lastname: Machluf
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D065150:Cellular Reprogramming; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000067996:RAW 264.7 Cells; D013552:Swine; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D007328:Insulin
keywords: Cell encapsulation; Diabetes; Extracellular matrix; Insulin-producing cells