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Longitudinal In Vivo Imaging and Quantification of Human Pancreatic Islet Grafting and Contributing Host Cells in the Anterior Eye Chamber
Published on: June 11, 2020
Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI
Ping Wang1, Christian Schuetz, Prashanth Vallabhajosyula
11 Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. 2 Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 3 Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA. 4 Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA.
Background:
Information regarding the longevity of transplanted pancreatic islet grafts could provide valuable information for treatment options. In our previous studies, we showed that isolated autologous pancreatic islets could be labeled with iron oxide nanoparticles and monitored after transplantation using MRI. Here, we report on in vivo monitoring of a secondary damage that occurs at the later stages because of allogeneic immune rejection.
Methods:
In the proof-of-principle studies, iron oxide-labeled autologous pancreatic islets were transplanted under the renal capsules of nonhuman primates. To demonstrate acute graft loss, the animals were injected with streptozotocin. Graft monitoring was performed by in vivo MRI. Next, iron oxide-labeled allogeneic islets were transplanted into the liver and monitored by MRI after withdrawal of immunosuppression.
Results:
In autologous model, we observed a pronounced drop in graft volume after streptozotocin challenge as assessed by MRI. In allogeneic model of islet transplantation, there was an initial islet loss after the procedure followed by relative stabilization of the graft volume. After immunosuppression was discontinued, there was a noticeable drop in graft volume that gradually continued during the course of the study. Importantly, the loss of graft volume observed on MR preceded the raise in blood glucose.
Conclusions:
This study demonstrated that in vivo MRI was able to reveal graft volume loss before any changes in blood glucose that can be measured by standard methods. We believe that these results could provide means for clinicians to follow islet fate noninvasively and longitudinally using clinically relevant scanners.
Insights
Magnetic resonance imaging (MRI) can noninvasively monitor transplanted pancreatic islet graft volume. This technique detects graft volume loss due to immune rejection before blood glucose changes occur, aiding clinical management.
Area of Science:
- Transplantation immunology
- Medical imaging
- Endocrinology
Background:
- Understanding pancreatic islet graft longevity is crucial for improving transplantation outcomes.
- Previous work demonstrated MRI tracking of iron oxide-labeled autologous pancreatic islets.
- This study investigates late-stage secondary damage from allogeneic immune rejection.
Purpose of the Study:
- To evaluate in vivo MRI for monitoring pancreatic islet graft volume changes.
- To assess MRI's ability to detect graft loss caused by immune rejection.
- To compare MRI findings with blood glucose levels in monitoring graft function.
Main Methods:
- Iron oxide-labeled autologous and allogeneic pancreatic islets were transplanted into nonhuman primates.
- Graft volume was monitored using in vivo MRI.
- Acute graft loss was induced in the autologous model using streptozotocin; immunosuppression was withdrawn in the allogeneic model.
Main Results:
- MRI showed a significant drop in autologous graft volume after streptozotocin injection.
- Allogeneic grafts showed initial loss, followed by stabilization, then a noticeable volume decrease after immunosuppression withdrawal.
- MRI-detected graft volume loss preceded detectable increases in blood glucose levels.
Conclusions:
- In vivo MRI can detect pancreatic islet graft volume loss earlier than standard blood glucose measurements.
- This noninvasive MRI approach allows longitudinal monitoring of islet graft fate.
- The findings support the use of clinically relevant MRI scanners for monitoring transplanted islet grafts.

