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Development of an Immunosuppression Free Cellular Transplantation Platform
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- Author(s) / Creator(s)
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NFRF Exploration awarded in 2020: While the global incidence of type 1 diabetes (T1D) continues to rise, it is now clear that transplantation of human pancreatic islets of Langerhans, into the patients’ liver, can successfully restore glycemic control. Despite marked progress in clinical islet transplantation, transplant approaches are limited to those with life-threatening hypoglycemic unawareness. The major obstacles that hinder the more inclusive use of beta cell replacement with human islets are the need for life-long toxic immunosuppression to overcome the fierce immune attack that occurs after transplantation and lack of sufficient human donors. The objective of this application seeks to test a highly innovative and multidisciplinary approach to tackle these vital roadblocks that plague the broad-spectrum application of this curative beta cell-based therapy.
Our research approach will attenuate the immunological and organ donor limitations associated beta cell transplantation. Our aim is to develop and test a cutting-edge minimally invasive transplant platform that combines a micro-and nano-porous thin film immune-isolating device, implanted under the skin, together with genetically altered immunomodulatory A20 islets to prevent immune destruction; eliminating the need for immunosuppression. To overcome the human organ donor supply, islets will be sourced from pigs serving as a ubiquitous islet supply. The following aims will aid in accomplishing this objective:
1) Optimize micro-and nanoporous device fabrication and genetic engineering of A20 expressing porcine islets,
2) Utilize our ‘immunosuppression free’ combination islet transplant approach in murine islet transplant model, and
3) Scale-up and test our ‘immunosuppression free’ combination islet transplant platform in a large animal porcine study.
This application leverages the specific expertise (clinical islet transplantation, biomaterial and genetic engineering, immunology, and commercialization) of our international team in a new, innovative and synergistic project. By subverting the immune response to an islet transplant with a combination of a retrievable, biocompatible, scalable encapsulation device with genetically engineered immunomodulating porcine islets, our results will increase the prevalence of insulin independence, led to long-term durable graft function, eliminated recipient complications associated with systemic immunosuppression and broaden the spectrum of T1D patients eligible to receive a curative. -
- Date created
- 2019-12-10
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- Type of Item
- Research Material
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- License
- ©️Pepper, Andrew. All rights reserved other than by permission. This document embargoed to those without UAlberta CCID until 2030.