TY - JOUR
T1 - Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques
AU - Bochenek, Matthew A.
AU - Veiseh, Omid
AU - Vegas, Arturo J.
AU - McGarrigle, James J.
AU - Qi, Meirigeng
AU - Marchese, Enza
AU - Omami, Mustafa
AU - Doloff, Joshua C.
AU - Mendoza-Elias, Joshua
AU - Nourmohammadzadeh, Mohammad
AU - Khan, Arshad
AU - Yeh, Chun Chieh
AU - Xing, Yuan
AU - Isa, Douglas
AU - Ghani, Sofia
AU - Li, Jie
AU - Landry, Casey
AU - Bader, Andrew R.
AU - Olejnik, Karsten
AU - Chen, Michael
AU - Hollister-Lock, Jennifer
AU - Wang, Yong
AU - Greiner, Dale L.
AU - Weir, Gordon C.
AU - Strand, Berit Løkensgard
AU - Rokstad, Anne Mari A.
AU - Lacik, Igor
AU - Langer, Robert
AU - Anderson, Daniel G.
AU - Oberholzer, Jose
N1 - Funding Information:
This work was supported jointly by the Chicago Diabetes Project and the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust (grant number 3-SRA-2014-285-M-R (R.L. and D.G.A.)), the US National Institutes of Health (grant numbers DK091526 (J.O.) EB000244 (R.L.), EB000351 (R.L.), DE013023 (R.L.), CA151884 (R.L.) and UC4DK104218 (D.L.G.)), and through a gift from the Tayebati Family Foundation (D.G.A. and R.L.). This work was also supported by the Slovak Research and Development Agency under contract number APVV-14-858 (I.L.). O.V. was supported by JDRF and Department of Defense Congressionally Directed Medical Research Program (DOD/CDMRP) postdoctoral fellowships (grant numbers 3-2013-178 and W81XWH-13-1-0215, respectively). J.C.D. was supported by a JDRF postdoctoral fellowship (grant number 3-PDF-2015-91-A-N). The authors acknowledge L. Halliday and the veterinary staff at the Biological Resource Laboratories at UIC for their assistance and technical support during the course of the studies. We thank R. Calafiore and G. Basta from the University of Perugia for producing the A-PLO-A spheres under current good manufacturing practice conditions at the University of Illinois at Chicago for the herein described experiments. We thank B. Tuch and his team at the Diabetes Transplant Unit, Prince of Wales Hospital, Sydney, Australia, for the production of the UPMVG-Ba2+ spheres and sharing his experience from the clinical trials in encapsulated islet transplant trials conducted in Sydney, Australia. We thank H. H. Tam for his advice on the statistical analysis of datasets.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/11/1
Y1 - 2018/11/1
N2 - The transplantation of pancreatic islet cells could restore glycaemic control in patients with type 1 diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in rodent models of diabetes; however, humans transplanted with equivalent microsphere formulations have experienced only transient islet graft function owing to a vigorous foreign-body response (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing in non-human primate (NHP) models of seven alginate formulations that were efficacious in rodents, including three that led to transient islet graft function in clinical trials. All formulations elicited significant FBR and PFO 1 month post implantation; however, three chemically modified, immune-modulating alginate formulations elicited a reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.
AB - The transplantation of pancreatic islet cells could restore glycaemic control in patients with type 1 diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in rodent models of diabetes; however, humans transplanted with equivalent microsphere formulations have experienced only transient islet graft function owing to a vigorous foreign-body response (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing in non-human primate (NHP) models of seven alginate formulations that were efficacious in rodents, including three that led to transient islet graft function in clinical trials. All formulations elicited significant FBR and PFO 1 month post implantation; however, three chemically modified, immune-modulating alginate formulations elicited a reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.
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U2 - 10.1038/s41551-018-0275-1
DO - 10.1038/s41551-018-0275-1
M3 - Article
C2 - 30873298
AN - SCOPUS:85052314119
SN - 2157-846X
VL - 2
SP - 810
EP - 821
JO - Nature biomedical engineering
JF - Nature biomedical engineering
IS - 11
ER -