TY - JOUR
T1 - Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion
AU - Galasso, Marcos
AU - Feld, Jordan J.
AU - Watanabe, Yui
AU - Pipkin, Mauricio
AU - Summers, Cara
AU - Ali, Aadil
AU - Qaqish, Robert
AU - Chen, Manyin
AU - Ribeiro, Rafaela V.P.
AU - Ramadan, Khaled
AU - Pires, Layla
AU - Bagnato, Vanderlei S.
AU - Kurachi, Cristina
AU - Cherepanov, Vera
AU - Moonen, Gray
AU - Gazzalle, Anajara
AU - Waddell, Thomas K.
AU - Liu, Mingyao
AU - Keshavjee, Shaf
AU - Wilson, Brian C.
AU - Humar, Atul
AU - Cypel, Marcelo
N1 - Funding Information:
This work was supported by the Canadian Institutes of Health Research (CIHR Project Grant), Medicine-by-Design Cycle 1 Team Projects Award (# C1TPA-2016–07), Toronto General & Western Hospital Foundation (Grant # 1013612) and XVIVO Perfusion. Financial support was also provided by the Brazilian agencies São Paulo Research Foundation (FAPESP CEPOF 2013/07276–1, INCT 2014/50857–8) and National Council for Scientific and Technological Development (CNPq 465360/2014–9). We thank Paul Chartrand (Latner Thoracic Surgery Laboratories) for supplies and logistics management, Natalia Mayumi Inada, José Dirceu Vollet-Filho, Mariana Carreira Geralde and Ilaiáli Souza Leite (IFSC-USP, SP, Brazil) for technical help, and Daisuke Nakajima, Ashish Patel and Hemant Gohkale (Latner Thoracic Surgery Laboratories) for assisting during EVLP and transplantation.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission. Physical viral clearance in combination with germicidal light-based therapies during normothermic ex-vivo Lung Perfusion (EVLP), a method for assessment and treatment of injured donor lungs, inactivates HCV virus in a short period of time. Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor organ during preservation could significantly increase the availability of organs for transplantation and encourages further clinical development.
AB - Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission. Physical viral clearance in combination with germicidal light-based therapies during normothermic ex-vivo Lung Perfusion (EVLP), a method for assessment and treatment of injured donor lungs, inactivates HCV virus in a short period of time. Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor organ during preservation could significantly increase the availability of organs for transplantation and encourages further clinical development.
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U2 - 10.1038/s41467-018-08261-z
DO - 10.1038/s41467-018-08261-z
M3 - Article
C2 - 30696822
AN - SCOPUS:85060784033
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 481
ER -