Tolerance of Vascularized Islet‐Kidney Transplants in Rhesus Monkeys

We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet‐kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hem...

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Bibliographic Details
Published in:American journal of transplantation 2017-01, Vol.17 (1), p.91-102
Main Authors: Pathiraja, V., Villani, V., Tasaki, M., Matar, A. J., Duran‐Struuck, R., Yamada, R., Moran, S. G., Clayman, E. S., Hanekamp, J., Shimizu, A., Sachs, D. H., Huang, C. A., Yamada, K.
Format: Article
Language:English
Subjects:
Animals
Autografts
Cyclosporins
Diabetes
Diabetes mellitus
Donors
Female
Graft rejection
Graft Rejection - immunology
Graft Rejection - prevention & control
Graft Survival - immunology
Hematopoietic stem cells
Hyperglycemia
Immune Tolerance - immunology
Immunological tolerance
Immunosuppression
Insulin
islet isolation
islet transplantation
Islets of Langerhans - blood supply
Islets of Langerhans Transplantation
Kidney - blood supply
Kidney Transplantation
kidney transplantation/nephrology
Kidney transplants
Kidneys
Leukapheresis
Lymphocytes T
Macaca mulatta
Male
Monkeys & apes
Pancreas
Pancreatic islet transplantation
Primates
Radiation
Stem cells
tolerance: chimerism
tolerance: experimental
translational research/science
Transplantation, Homologous
Transplants & implants
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Summary:We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet‐kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cell (HSC) Tx in an attempt to induce tolerance in nonhuman primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IK Tx. HSC Tx was performed after mobilization and leukapheresis of the donors and conditioning of the recipients with total body irradiation, T cell depletion, and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IK Tx was performed either 20–22 (n = 3) or 208 (n = 1) days after HSC Tx. All animals accepted IKs without rejection. All recipients required >20 U/day insulin before IK Tx to maintain
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.13952