title: Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI.
abstract: 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.
authors: 1 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.
authors: Ping
authors: P
authors: Wang
authors: Christian
authors: C
authors: Schuetz
authors: Prashanth
authors: P
authors: Vallabhajosyula
authors: Zdravka
authors: Z
authors: Medarova
authors: Aseda
authors: A
authors: Tena
authors: Lingling
authors: L
authors: Wei
authors: Kazuhiko
authors: K
authors: Yamada
authors: Shaoping
authors: S
authors: Deng
authors: James F
authors: JF
authors: Markmann
authors: David H
authors: DH
authors: Sachs
authors: Anna
authors: A
authors: Moore
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000097:blood / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D009929:Organ Size; D048529:Papio hamadryas; D011237:Predictive Value of Tests; D013311:Streptozocin; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D003287:Contrast Media; D003911:Dextrans; D007166:Immunosuppressive Agents; D058185:Magnetite Nanoparticles; D013311:Streptozocin; C065507:ferumoxides