2011 - IPITA - Prague


Parallel session 15 – Open oral presentations Topic: Experimental islet transplantation: Immunology

15.7 - Long-term islet allograft survival by peri-transplant antioxidant therapy combined with LFA-1 blockade

Presenter: C., Fotino, Miami, USA
Authors: C. Fotino, R. Damaris Molano, E. Zahr-Akrawi, J. Molina, M. Lopez-Cabezas, G. Merizzi, A. Soleti, L. Inverardi, C. Ricordi, A. Pileggi



Long-term islet allograft survival by peri-transplant antioxidant therapy combined with LFA-1 blockade

C. Fotino1, R. Damaris Molano1, E. Zahr-Akrawi1, J. Molina1, M. Lopez-Cabezas1, G. Merizzi2, A. Soleti2, L. Inverardi1, C. Ricordi3, A. Pileggi4
1 Diabetes Research Institute, University of Miami, Miami, USA; 2 Medestea Research, Turin, Italy; 3 University of Miami / Diabetes Research Institute, Departments of Surgery, Medicine, Microbiology & Immunology, and Biomedical Engineering; Jackson Memorial Hospital – and University of Miami Transplant Institute, Miami, USA; 4 University of Miami / Diabetes Research Institute, Departments of Surgery, Microbiology & Immunology, Miami, USA

Objective: To evaluate the impact on islet allograft survival of antioxidant therapy in combination with blockade of Lymphocyte Function Associated Antigen-1 (LFA-1) in a fully MHC-mismatched allogeneic islet transplantation model.

Methods: C56BL/6 (H-2b) mice were rendered diabetic with streptozotocin and then received under the kidney capsule DBA/2(H-2d) islets pre-cultured or not with the antioxidant Decanedioicacid bis(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)diester dihydrochloride(Iacvita, IAC; 100uM). Recipient treatments consisted of intraperitoneal administration of 100ug daily for 1 week of anti-LFA-1 antibody (KBA clone) and/or 15-day antioxidant treatment with 15mg/kg/day IAC. Control mice received no treatment or vehicle. Graft survival was monitored on nonfasting glycemic values (rejection was defined as NFG<200mg/dL).

Results: IAC treatment alone was associated with a MST of 7 (6-100)and 17 (12-19) days (n=3 and 4, respectively with or without in vitro IAC; p=N.S.). Anti-LFA-1 alone resulted in long-term (>100 days) survival in 62.5% of the recipients (n=8; p=0.03 vs. control). Combinatorial treatment yielded 100% long-term (>100 days) graft survival (n=3 and n=4,respectively, with or without in vitro IAC; p<0.014 vs. control; p<0.03vs. IAC). Control animals rejected their grafts with a median survival time (MST) of 15 (range7-24) days (n=12).

Conclusions: Peri-transplant treatment with anti-LFA-1 antibody results in long-term survival of islet allografts in only a proportion of the recipients. Combinatorial treatment of anti-LFA-1 Ab with IAC, an antioxidant drug, resulted synergistic in this model with all animals maintaining a functional graft long-term. The use of antioxidants, such as IAC, may represent a viable strategy to enhance the success of tolerance inducing protocols.


You must be logged in to view recordings

Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.