Murine animal models for preclinical islet transplantation

Abstract

Advances in islet transplantation research have led to remarkable improvements in the outcome in humans with type 1 diabetes. However, pitfalls, mainly linked both to early liver-specific inflammatory events and to pre-existing and transplant-induced auto- and allo-specific adaptive immune responses, still remain. In this scenario research into pancreatic islet transplantation, essential to investigate new strategies to overcome open issues, needs very well-designed preclinical studies to obtain consistent and reliable results and select only promising strategies that may be translated into the clinical practice. This review discusses the main shortcomings of the mouse models currently used in islet transplantation research, outlining the main factors and variables to take into account for the design of new preclinical studies. Since several parameters concerning both the graft (i.e., islets) and the recipient (i.e., diabetic mice) may influence transplant outcome, we recommend considering several critical points in designing future bench-to-bedside islet transplantation research.

Keywords: :

• equivalent islet
• hyperglycemia
• intra-hepatic islet infusion
• islet transplantation
• preclinical model
• type 1 diabetes

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by the EU (HEALTH-F5-2009-241883- BetaCellTherapy). E. Cantarelli conducted this study as part of her PhD in Molecular Medicine, Program in Basic and Applied Immunology, San Raffaele University. A. Citro is a PhD student with the Department of Surgery at the University of Pavia.