Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/142343
Title: Translational assessment of a genetic engineering methodology to improve islet function for transplantation
Authors: van Krieken, Pim P.
Voznesenskaya, Anna
Dicker, Andrea
Xiong, Yan
Park, Jae Hong
Lee, Jeong Ik
Ilegems, Erwin
Berggren, Per-Olof
Keywords: Science::Medicine
Issue Date: 2019
Source: van Krieken, P. P., Voznesenskaya, A., Dicker, A., Xiong, Y., Park, J. H., Lee, J. I., . . . Berggren, P.-O. (2019). Translational assessment of a genetic engineering methodology to improve islet function for transplantation. EBioMedicine, 45, 529-541. doi:10.1016/j.ebiom.2019.06.045
Journal: EBioMedicine
Abstract: Background: The functional quality of insulin-secreting islet beta cells is a major factor determining the outcome of clinical transplantations for diabetes. It is therefore of importance to develop methodological strategies aiming at optimizing islet cell function prior to transplantation. In this study we propose a synthetic biology approach to genetically engineer cellular signalling pathways in islet cells. Methods: We established a novel procedure to modify islet beta cell function by combining adenovirus-mediated transduction with reaggregation of islet cells into pseudoislets. As a proof-of-concept for the genetic engineering of islets prior to transplantation, this methodology was applied to increase the expression of the V1b receptor specifically in insulin-secreting beta cells. The functional outcomes were assessed in vitro and in vivo following transplantation into the anterior chamber of the eye. Findings: Pseudoislets produced from mouse dissociated islet cells displayed basic functions similar to intact native islets in terms of glucose induced intracellular signalling and insulin release, and after transplantation were properly vascularized and contributed to blood glucose homeostasis. The synthetic amplification of the V1b receptor signalling in beta cells successfully modulated pseudoislet function in vitro. Finally, in vivo responses of these pseudoislet grafts to vasopressin allowed evaluation of the potential benefits of this approach in regenerative medicine. Interpretation: These results are promising first steps towards the generation of high-quality islets and suggest synthetic biology as an important tool in future clinical islet transplantations. Moreover, the presented methodology might serve as a useful research strategy to dissect cellular signalling mechanisms of relevance for optimal islet function.
URI: https://hdl.handle.net/10356/142343
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2019.06.045
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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