TY - JOUR
T1 - Abandon the mouse research ship? Not just yet!
AU - Osuchowski, Marcin F.
AU - Remick, Daniel G.
AU - Lederer, James A.
AU - Lang, Charles H.
AU - Aasen, Ansgar O.
AU - Aibiki, Mayuki
AU - Azevedo, Luciano C.
AU - Bahrami, Soheyl
AU - Boros, Mihaly
AU - Cooney, Robert
AU - Cuzzocrea, Salvatore
AU - Jiang, Yong
AU - Junger, Wolfgang G.
AU - Hirasawa, Hiroyuki
AU - Hotchkiss, Richard S.
AU - Li, Xiang An
AU - Radermacher, Peter
AU - Redl, Heinz
AU - Salomao, Reinaldo
AU - Soebandrio, Amin
AU - Thiemermann, Christoph
AU - Vincent, Jean Louis
AU - Ward, Peter
AU - Yao, Yong Ming
AU - Yu, Huang Ping
AU - Zingarelli, Basilia
AU - Chaudry, Irshad H.
PY - 2014/6
Y1 - 2014/6
N2 - Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.
AB - Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.
KW - Mouse models of critical illness
KW - burn
KW - endotoxemia
KW - sepsis
KW - trauma
UR - http://www.scopus.com/inward/record.url?scp=84901626481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901626481&partnerID=8YFLogxK
U2 - 10.1097/SHK.0000000000000153
DO - 10.1097/SHK.0000000000000153
M3 - Review article
C2 - 24569509
AN - SCOPUS:84901626481
VL - 41
SP - 463
EP - 475
IS - 6
ER -