The combination of donor pretreatment with cyclophosphamide, organ culture in 95% O2:5% CO2 for 7–10 days, and short-term immunosuppression of recipients with cyclosporin A (CsA) were necessary to obtain 100% survival of single-cluster BALB/c islet allografts in outbred mice. In vivo and in vitro pretreatment of the donor tissue alone resulted in the acceptance of 45% of the islet allografts in nonimmunosuppressed outbred mice. CsA treatment of recipients alone yielded 40% survival of the untreated allografts. CsA treatment played an important role in maintaining the capacity of islet allografts to function in outbred mice. During CsA treatment, 88% of streptozocin-treated mice showed graft-dependent reversal of diabetes; the remainder showed no evidence of graft function, and CsA treatment failed to prevent acute graft rejection. After withdrawal of CsA immunosuppression, 38% of this total group remained normoglycemic. These findings suggest that modulation of both donor-tissue immunogenicity and recipient responsiveness will be required for successful pancreatic islet transplantation in diabetic humans.
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Original Contributions|
December 01 1986
Reversal of Diabetes in Outbred Mice by Islet Allotransplantation Free
C J Simeonovic;
C J Simeonovic
Transplantation Biology Unit, Department of Medicine and Clinical Science, the John Curtin School of Medical Research, Australian National University
Australia
Departments of Microbiology and Immunology and Pediatrics, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
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S J Prowse;
S J Prowse
Transplantation Biology Unit, Department of Medicine and Clinical Science, the John Curtin School of Medical Research, Australian National University
Australia
Departments of Microbiology and Immunology and Pediatrics, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
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K J Lafferty
K J Lafferty
Transplantation Biology Unit, Department of Medicine and Clinical Science, the John Curtin School of Medical Research, Australian National University
Australia
Departments of Microbiology and Immunology and Pediatrics, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
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Address reprint requests to Dr. Charmaine J. Simeonovic, The Transplantation Biology Unit, Department of Medicine and Clinical Science, The John Curtin School of Medical Research, Australian National University, G.P.O. Box 334, Canberra 2600, A.C.T., Australia.
Diabetes 1986;35(12):1345–1349
Article history
Received:
March 24 1986
Revision Received:
July 02 1986
PubMed:
3095165
Citation
C J Simeonovic, S J Prowse, K J Lafferty; Reversal of Diabetes in Outbred Mice by Islet Allotransplantation. Diabetes 1 December 1986; 35 (12): 1345–1349. https://doi.org/10.2337/diab.35.12.1345
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