טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentShafir Oded
SubjectEngineered Vascular Milieu for Pancreatic Islets Support
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Shulamit Levenberg
Full Thesis textFull thesis text - English Version


Abstract

Islets transplantation is a promising therapeutic strategy for type 1 diabetic patients. However, isolating the islets from the donor`s pancreas results in extensive damage to their vasculature. This damage prolongs the revascularization in the recipient and causes islets dysfunction. In order to facilitate the revascularization prior to implantation, we developed an engineered pancreatic tissue. This tissue consists of pancreatic islets, seeded with fibroblasts and endothelial cells on a highly porous biodegradable scaffold (1:1 PLLA/PLGA). Under these conditions, the fibroblasts and endothelial cells have been shown to form a blood-vessel-like network. This network may support the islets and prevent their dysfunction. Three different culturing strategies were chosen: 1. `Step-by-step` Seeding - Fibroblasts and endothelial cells were seeded, allowing the formation of blood vessel network, followed by seeding pancreatic islets. By that minimizing the time islets are separated from vasculature. 2. `Simultaneous` Seeding - Fibroblasts, endothelial cells and islets were all seeded at the same time, allowing the blood vessel network to self-assemble in the presence of the islets. In these two strategies in vitro and in vivo studies were performed. After an incubation period a perfusion problem evolved, drastically reducing the tissue activity. A third strategy was then applied to confront this obstacle. 3. `Direct perfusion` - After simultaneous seeding, the tissue was subjected to flow conditions to increase perfusion. Under these flow conditions the perfusion problem was avoided, yet further research is required to determine the proper conditions needed for the support of the islets long-term activity.