Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation.

Olariu, Radu; Denoyelle, Julie Sophie Cécile; Leclère, Franck-Marie Patrick; Dzhonova, Dzhuliya Vihrenova; Gajanayake, Thusitha; Banz Wälti, Yara; Hayoz, Michael; Constantinescu, Mihai Adrian; Rieben, Robert; Vögelin, Esther; Taddeo, Adriano (2017). Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation. The journal of surgical research, 218, pp. 49-57. Elsevier 10.1016/j.jss.2017.05.046

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BACKGROUND Immunosuppressive therapies derived from solid organ transplantation are effective in promoting survival of vascularized composite allotransplantation (VCA), but they cause serious side effects that are difficult to justify for this non-life-saving procedure. Unlike solid organ transplantation, hand and face transplants offer the possibility of site-specific immunosuppression for reducing systemic exposure while increasing intra-graft concentrations of the drug. Therefore, in this study, we tested whether a single intra-graft injection tacrolimus could promote VCA survival. METHODS Brown Norway-to-Lewis hind limb transplantations were performed, and animals were left untreated (group I), treated with a daily injection of 1-mg/kg tacrolimus for 21 days (group 2) or injected with 7-mg tacrolimus directly into the transplanted limb on day 1 (group III). Graft rejection was monitored, and animals were sacrificed at grade 3 rejection or 200 days after transplantation. RESULTS Intra-graft injection of tacrolimus significantly prolonged allograft survival as compared to untreated animals or animals treated with systemic tacrolimus. Half of the intra-graft-treated rats rejected their graft on average at day 70.5. Interestingly, the other half remained rejection-free for more than 200 days without signs of kidney or liver toxicity. In these animals, tacrolimus was detected in the VCA skin but not in the blood until day 200. Long-term survival was not linked to induction of donor-specific tolerance but to a higher level of lymphocyte chimerism. CONCLUSIONS Intra-graft delivery of tacrolimus may promote VCA survival by increasing tissue drug availability and promoting the establishment of transient chimerism and thus long-term graft acceptance.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Handchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Plastische Chirurgie
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Olariu, Radu; Denoyelle, Julie Sophie Cécile; Leclère, Franck-Marie Patrick; Dzhonova, Dzhuliya Vihrenova; Gajanayake, Thusitha; Banz Wälti, Yara; Constantinescu, Mihai Adrian; Rieben, Robert; Vögelin, Esther and Taddeo, Adriano

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1095-8673

Publisher:

Elsevier

Language:

English

Submitter:

Veronika Picha

Date Deposited:

31 Oct 2017 10:11

Last Modified:

15 Feb 2019 09:08

Publisher DOI:

10.1016/j.jss.2017.05.046

PubMed ID:

28985877

Uncontrolled Keywords:

Drug delivery Rat hind limb transplantation Tacrolimus Vascularized composite allotransplantation

BORIS DOI:

10.7892/boris.106270

URI:

https://boris.unibe.ch/id/eprint/106270

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