Kupffer Cell Transplantation in Mice for Elucidating Monocyte/Macrophage Biology and for Potential in Cell or Gene Therapy

The American Journal of Pathology
Simone MerlinSanjeev Gupta

Abstract

Kupffer cells (KC) play major roles in immunity and tissue injury or repair. Because recapitulation of KC biology and function within liver will allow superior insights into their functional repertoire, we studied the efficacy of the cell transplantation approach for this purpose. Mouse KC were isolated from donor livers, characterized, and transplanted into syngeneic recipients. To promote cell engraftment through impairments in native KC, recipients were preconditioned with gadolinium chloride. The targeting, fate, and functionality of transplanted cells were evaluated. The findings indicated that transplanted KC engrafted and survived in recipient livers throughout the study period of 3 months. Transplanted KC expressed macrophage functions, including phagocytosis and cytokine expression, with or without genetic modifications using lentiviral vectors. This permitted studies of whether transplanted KC could affect outcomes in the context of acetaminophen hepatotoxicity or hepatic ischemia-reperfusion injury. Transplanted KC exerted beneficial effects in these injury settings. The benefits resulted from cytoprotective factors including vascular endothelial growth factor. In conclusion, transplanted adult KC were successfully t...Continue Reading

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Citations

May 30, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Simone MerlinAntonia Follenzi
Jan 21, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Daniel BentenSanjeev Gupta
Sep 8, 2019·Cells·Andrey V ElchaninovGennady T Sukhikh
Nov 7, 2019·Cancers·Anna RossettoMatteo Cescon
Sep 2, 2020·International Journal of Molecular Sciences·Cristina OlgasiAntonia Follenzi
Mar 25, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Luqi DuanAnup Ramachandran
Mar 9, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Preeti ViswanathanSanjeev Gupta
Aug 31, 2021·Biochemistry and Biophysics Reports·Wen-Ling LinTakashi Sakai

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