The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice

Abstract

Aims/hypothesis In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. Methods We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time.Results The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. Conclusions/interpretation Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.

Magnetic particle imaging of islet transplantation in the liver and under the kidney capsule in mouse models

“…We believe that MPI could assist researcher and clinicians in detecting grafts from various sources and monitoring them over time. Finally, as islet Tx surgeons try to find sites more suitable for islet survival (47,48), the approach described above could assist in establishing those new sites.…”

Anakinra and Tocilizumab Enhance Survival and Function of Human Islets during Culture: Implications for Clinical Islet Transplantation

“…The preferred transplantation site for islets still is the intraportal vein despite early posttransplantation complications and islet loss and is due to low oxygen tension, an active innate immune system, provocation of an inflammatory response (IBMIR) and the toxic use of immunosuppressive drugs. Several alternative transplantation sites have been evaluated 231 232 and there is a continuous search for a more optimal site [233][234][235] . Until such a site has been found we have to continue to do our best for the islets to survive in an intrahepatic environment.…”

The eye as a novel imaging site in diabetes research

“…The highly viable and fully functional islets and other tissues/organs engrafted in the ACE become accessible to microscopy (Abdulreda et al, 2013; Almaca et al, 2014; Almaca, Weitz, Rodriguez-Diaz, Pereira, & Caicedo, 2018; Cohrs et al, 2017; Diez et al, 2017; Ilegems et al, 2013; Ilegems et al, 2015; Kemter et al, 2017; Kragl et al, 2016; Lee et al, 2018; Leibiger et al, 2010; Leibiger et al, 2012; Leibiger & Berggren, 2017; Mojibian et al, 2013; Nyqvist et al, 2011; Perez et al, 2011; Rodriguez-Diaz et al, 2012; Rodriguez-Diaz et al, 2018; Speier, 2011; Speier, Nyqvist, Cabrera, et al, 2008; Speier, Nyqvist, Kohler, et al, 2008; van Krieken et al, 2017). Importantly, morphological and functional profiles detected in vivo reflect true physiological and pathological situations (Abdulreda et al, 2011; Abdulreda et al, 2013; Abdulreda et al, 2016; Abdulreda & Berggren, 2013; Ali et al, 2016; Almaca et al, 2014; Almaca et al, 2018; Avall et al, 2015; Bader et al, 2016; Berclaz et al, 2016; Borg et al, 2014; Chen et al, 2016; Chmelova et al, 2015; Cohrs et al, 2017; Diez et al, 2017; Faleo et al, 2014; Ilegems et al, 2013; Ilegems et al, 2015; Johansson et al, 2015; Juntti-Berggren et al, 2015; Kemter et al, 2017; Kragl et al, 2016; Lee et al, 2018; Leibiger et al, 2010; Leibiger et al, 2012; Leibiger & Berggren, 2017; Miska et al, 2014; Mojibian et al, 2013; Nyqvist et al, 2011; Paschen et al, 2016; Paschen et al, 2018; Perez et al, 2011; Rodriguez-Diaz et al, 2012; Rodriguez-Diaz et al, 2018; Schmidt-Christensen et al, 2013; Shalaly et al, 2016; Speier, 2011; Speier, Nyqvist, Cabrera, et al, 2008; Speier, Nyqvist, K...…”

“…2) (Speier et al, 2008; Speier et al, 2008). We have succeeded in developing the nearly non-invasive technique for transplanting islets into the ACE and the ACE-based imaging technique for visualizing intraocular islets under healthy and diabetic conditions in a non-invasive, longitudinal and in vivo real-time manner (Abdulreda et al, 2011; Abdulreda & Berggren, 2013; Abdulreda, Caicedo, & Berggren, 2013; Abdulreda, Rodriguez-Diaz, Caicedo, & Berggren, 2016; Ali et al, 2016; Almaca et al, 2014; Avall et al, 2015; Diez et al, 2017; Faleo, Berggren, & Pileggi, 2014; Ilegems et al, 2013; Ilegems et al, 2015; Johansson et al, 2015; Juntti-Berggren, Ali, & Berggren, 2015; Lee et al, 2018; Leibiger et al, 2012; Leibiger & Berggren, 2017; Leibiger, Brismar, & Berggren, 2010; Miska et al, 2014; Nyqvist et al, 2011; Paschen et al, 2016; Paschen et al, 2018; Perez et al, 2011; Rodriguez-Diaz et al, 2012; Rodriguez-Diaz et al, 2018; Schmidt-Christensen et al, 2013; Shalaly et al, 2016; Speier, Nyqvist, Cabrera, et al, 2008; Speier, Nyqvist, Kohler, et al, 2008; van Krieken et al, 2017). We and others have tackled a series of issues in the diabetes arena by employing the ACE technology (Fig.…”