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Renal allograft tolerance in DLA-identical and haploidentical dogs after nonmyeloablative conditioning and transient immunosuppression with cyclosporine and mycophenolate mofetil.
Transplant Proc. 2005 Dec; 37(10):4579-86.TP

Abstract

BACKGROUND

Canine models of bone marrow and renal transplantation have provided important preclinical data relevant to developing novel therapeutic protocols for hematopoietic and solid organ transplantation in human beings. Nonmyeloablative transplantation has been shown to induce stable mixed hematopoietic chimerism in normal dogs and correct the phenotype of canine pyruvate kinase deficiency and Glanzman's thrombasthenia. In this study, we investigated the potential for inducing renal allograft tolerance using a nonmyeloablative bone marrow transplantation strategy that induces mixed chimerism in DLA-identical dogs.

METHODS

Reciprocal renal allografts were performed in 4 DLA-identical and 4 DLA-haploidentical dogs with nonmyeloablative conditioning (200 cGy total body irradiation [TBI]) and transient immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) with and without simultaneous bone marrow transplantation. Two DLA-identical control dogs received reciprocal renal allografts without TBI or immunosuppression with CSP and MMF. Serum creatinine (Cr) concentration was monitored to assess renal allograft function.

RESULTS

The renal allografts were acutely rejected in the 2 DLA-identical dogs without TBI or immunosuppression. There was long-term (>1 year) renal allograft survival as evidenced by a normal (<2.0 mg/dL) serum Cr concentration in both the DLA-identical and DLA-haploidentical dogs that underwent 200 cGy TBI and transient immunosuppression with CSP and MMF either with or without simultaneous bone marrow transplantation.

CONCLUSIONS

Nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with CSP and MMF induce renal allograft tolerance in DLA-identical and DLA-haploidentical dogs without donor/host mixed hematopoietic chimerism. These findings suggest it may be possible to induce tolerance to solid organ transplants without the need for chronic immunosuppressive therapy or stable hematopoietic chimerism in the setting of both DLA-matched and haploidentical transplants.

Authors+Show Affiliations

College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16387175

Citation

Niemeyer, G P., et al. "Renal Allograft Tolerance in DLA-identical and Haploidentical Dogs After Nonmyeloablative Conditioning and Transient Immunosuppression With Cyclosporine and Mycophenolate Mofetil." Transplantation Proceedings, vol. 37, no. 10, 2005, pp. 4579-86.
Niemeyer GP, Welch JA, Tillson M, et al. Renal allograft tolerance in DLA-identical and haploidentical dogs after nonmyeloablative conditioning and transient immunosuppression with cyclosporine and mycophenolate mofetil. Transplant Proc. 2005;37(10):4579-86.
Niemeyer, G. P., Welch, J. A., Tillson, M., Brawner, W., Rynders, P., Goodman, S., Dufresne, M., Dennis, J., & Lothrop, C. D. (2005). Renal allograft tolerance in DLA-identical and haploidentical dogs after nonmyeloablative conditioning and transient immunosuppression with cyclosporine and mycophenolate mofetil. Transplantation Proceedings, 37(10), 4579-86.
Niemeyer GP, et al. Renal Allograft Tolerance in DLA-identical and Haploidentical Dogs After Nonmyeloablative Conditioning and Transient Immunosuppression With Cyclosporine and Mycophenolate Mofetil. Transplant Proc. 2005;37(10):4579-86. PubMed PMID: 16387175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal allograft tolerance in DLA-identical and haploidentical dogs after nonmyeloablative conditioning and transient immunosuppression with cyclosporine and mycophenolate mofetil. AU - Niemeyer,G P, AU - Welch,J A, AU - Tillson,M, AU - Brawner,W, AU - Rynders,P, AU - Goodman,S, AU - Dufresne,M, AU - Dennis,J, AU - Lothrop,C D,Jr PY - 2005/03/17/received PY - 2006/1/3/pubmed PY - 2006/3/3/medline PY - 2006/1/3/entrez SP - 4579 EP - 86 JF - Transplantation proceedings JO - Transplant. Proc. VL - 37 IS - 10 N2 - BACKGROUND: Canine models of bone marrow and renal transplantation have provided important preclinical data relevant to developing novel therapeutic protocols for hematopoietic and solid organ transplantation in human beings. Nonmyeloablative transplantation has been shown to induce stable mixed hematopoietic chimerism in normal dogs and correct the phenotype of canine pyruvate kinase deficiency and Glanzman's thrombasthenia. In this study, we investigated the potential for inducing renal allograft tolerance using a nonmyeloablative bone marrow transplantation strategy that induces mixed chimerism in DLA-identical dogs. METHODS: Reciprocal renal allografts were performed in 4 DLA-identical and 4 DLA-haploidentical dogs with nonmyeloablative conditioning (200 cGy total body irradiation [TBI]) and transient immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) with and without simultaneous bone marrow transplantation. Two DLA-identical control dogs received reciprocal renal allografts without TBI or immunosuppression with CSP and MMF. Serum creatinine (Cr) concentration was monitored to assess renal allograft function. RESULTS: The renal allografts were acutely rejected in the 2 DLA-identical dogs without TBI or immunosuppression. There was long-term (>1 year) renal allograft survival as evidenced by a normal (<2.0 mg/dL) serum Cr concentration in both the DLA-identical and DLA-haploidentical dogs that underwent 200 cGy TBI and transient immunosuppression with CSP and MMF either with or without simultaneous bone marrow transplantation. CONCLUSIONS: Nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with CSP and MMF induce renal allograft tolerance in DLA-identical and DLA-haploidentical dogs without donor/host mixed hematopoietic chimerism. These findings suggest it may be possible to induce tolerance to solid organ transplants without the need for chronic immunosuppressive therapy or stable hematopoietic chimerism in the setting of both DLA-matched and haploidentical transplants. SN - 0041-1345 UR - https://www.unboundmedicine.com/medline/citation/16387175/Renal_allograft_tolerance_in_DLA_identical_and_haploidentical_dogs_after_nonmyeloablative_conditioning_and_transient_immunosuppression_with_cyclosporine_and_mycophenolate_mofetil_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(05)01154-1 DB - PRIME DP - Unbound Medicine ER -