Dian Arifin PhD, Abstract Co-Author: Nothing to Disclose

Mangesh Kulkarni, Abstract Co-Author: Nothing to Disclose

Jeff W.M. Bulte PhD, Presenter: Research Grant, Koninklijke Philips NV Founder and co-owner, SenCEST, LLC

To immuno-isolate transplanted human islet cells by encapsulation and to apply fluorine as 19F MRI tracer for predicting islet cell survival with and without co-transplantation of immunomodulating mesenchymal stem cells (MSCs).

Fluorocapsules were synthesized by adding 6% v/v PFPE into semi-permeable alginate microcapsules and used to encapsulate luciferase-transfected fresh cadaveric human islets or mouse insulinoma cells. Human MSCs were encapsulated separately in non-modified capsules. 5000 encapsulated islets without (n=6) or with 50,000 encapsulated MSCs (n=6 each) were engrafted s.c. into diabetic NOD/ShiLtj mice. For 19F MRI of capsule rupture, fluorocapsules degradable by alginate lyase were used. Controls were mice receiving no alginate lyase or unencapsulated (naked) cells (n=5 each). Mice were imaged with an 11.7T scanner using a dual-tuned 1H/19F surface coil and an IVIS Spectrum /CT scanner for bioluminescence imaging (BLI) to monitor graft viability. 19F MR-signals were quantified using Voxel Tracker software (Celsense). Statistical analysis: Student’s t-test with p<0.05.

BLI signals in islet+MSC group were higher (p<0.05) compared to islets alone group (Fig.1A), with a transient improvement in glycemic control up to day 7 post-transplantation (Fig.1B). While 50% of mice transplanted with islets alone survived at 4 weeks, islet+MSC mice had 100% survival rate. Fluorocapsules appeared as hot spots on 1H/19F MRI (Fig.1C). 19F MRI signal from ruptured fluorocapsules correlated to graft failure (Fig.1D, p<0.05). Fluorine and BLI signals of intact fluorocapsules were stable, while naked cells were rejected within the same time as lysed capsules (Fig.1E,F).

MSCs rescued islets from early loss and transiently improved their function in a stringent s.c. transplantation environment. The decrease in 19F MRI signal upon capsule rupture proceeds concurrently with graft rejection and can be used to predict islet therapy failure.

19F MRI combined with MSCs can monitor and prevent islet cell graft failure for treatment of type I diabetes.

Arifin, D, Kulkarni, M, Bulte, J, 19F MRI of Fluorocapsules Predicts Failure of Islet Cell Therapy.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14010655.html