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Ex vivo intranodal administration of sirolimus
Affiliation:1. Albany Medical Center, Albany, NY, United States of America;2. George Mason University, Fairfax, VA, United States of America;3. University of Cincinnati Medical Center, Cincinnati, OH, United States of America;4. Erie County Medical Center, Buffalo, NY, United States of America;1. Department of Lung Cancer Surgery, Tianjin Medical University General Hospital; Anshan Road No.154, Heping District, Tianjin 300052, China;2. Department of Pediatric Surgery, Tianjin Children''s Hospital, No.238 LongYan Road, Tianjin 300134, China;3. Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Qixiangtai Road, No.22, Heping District, Tianjin 300070, China;1. Clinical Hospital, Kidney Transplant Unit, Belo Horizonte, MG, Brazil;2. Faculty of the Hospital Santa Casa, Belo Horizonte, MG, Brazil;3. IMUNOLAB – Laboratory of Transplant Immunology, Belo Horizonte, MG, Brazil;4. Faculty of Medical Sciences of Minas Gerais, Belo Horizonte, MG, Brazil;5. Clinical Hospital of Porto Alegre, Rio Grande do Sul, Brazil;6. Mater Dei Hospital Minas Gerais, Belo Horizonte, MG, Brazil;7. Biocor Hospital, Belo Horizonte, Minas Gerais, Brazil;1. Barcelona Tissue Bank, Banc de Sang i Teixits (BST), Barcelona, Spain;2. Arthroscopy Unit, Department of Orthopaedics, Hospital Clinic de Barcelona, Barcelona, Spain;3. Biomedical Research Institute (IIB-Sant Pau; SGR1113), Barcelona, Spain;4. Vall d''Hebron Institute of Research (VHIR), Barcelona, Spain;1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran;3. Nephrology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Abstract:BackgroundImmune-mediated adverse effects of current systemic immunosuppression therapy compromise long-term survival of liver transplant recipients. Our recently observed results showed that intranodal delivery of sirolimus induced interleukin (IL)-10–driven CD4+ CD25+ Foxp3+ regulatory T cells. The present report investigated the feasibility of intra-nodal delivery of sirolimus ex vivo into a human liver common bile duct lymph node.MethodsWe used a discarded donor human liver to directly administer sirolimus into a distal common bile duct lymph node. Sirolimus was injected once using an ultrasound-guided method.ResultsThe porta hepatis and its lymph node along the distal common bile duct were exposed. A handheld ultrasound probe (L15-7io, Koninklijke Philips N.V.) with a layer of standoff Aquasonic 100 Ultrasound Transmission Gel (Parker Laboratories, Inc) was applied to the exposed lymph node. Using a 1.0-mL 25G hypodermic needle, 0.05 mL of sirolimus solution was injected directly into the exposed lymph node.ConclusionsUnder sonographic guidance, direct injection of sirolimus into a hepatic draining lymph node along the common bile duct is accomplished precisely and reliably. Direct administration of therapeutic agents into local lymph nodes is a viable approach for effective targeted immunotherapy.
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