AUDE RUBIO |
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CORE FACILITY ORGANOID
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research/project
Development and analysis of 3D organoid primocultures
A major breakthrough during the last decade has been the establishment of 3D organoids models derived from either murine or human tissues. These models are based on the tissue stem cell capacities to reconstitute the diversity of the tissue cell populations. Tissue stem cells require unique niche microenvironments, thus, once in the presence of specific combinations of niche factors and once embedded in a 3D matrix, mouse and human epithelial tissues from different organs, like stomach, small intestine, colon, pancreas duct, liver ducts and bladder can efficiently form organoids (Barker et al., 2010; Boj et al., 2015; Huch et al., 2013; Sato et al., 2011; Varley CL et al., 2011). These 3D organoid models represent great interest for both basic and translational research.
This mini-organ culture system can be applied to healthy as well as diseased tissues (aka inflammation and cancer). During tumorigenesis, for instance, niche factors often become dispensable leading to a less stringent culture condition for cancer organoids as compared to healthy normal organoids. Established cancer organoids can be xenotransplanted to recapitulate histopathology of the parental tumor from which they are derived. Cancer organoids have been shown to reflect genetic lesions and gene expression patterns, opening up a possibility of in vitro drug testing for the prediction of clinical treatment response in patients.
Thus, biobanking of organoids derived from diseased tissues will help to unravel the pathogenesis of disease and the development of new diagnostic tools and new drugs. Our institute is currently setting up such a biobank for colon tissues from healthy, IBD and cancer patients.
A major breakthrough during the last decade has been the establishment of 3D organoids models derived from either murine or human tissues. These models are based on the tissue stem cell capacities to reconstitute the diversity of the tissue cell populations. Tissue stem cells require unique niche microenvironments, thus, once in the presence of specific combinations of niche factors and once embedded in a 3D matrix, mouse and human epithelial tissues from different organs, like stomach, small intestine, colon, pancreas duct, liver ducts and bladder can efficiently form organoids (Barker et al., 2010; Boj et al., 2015; Huch et al., 2013; Sato et al., 2011; Varley CL et al., 2011). These 3D organoid models represent great interest for both basic and translational research.
This mini-organ culture system can be applied to healthy as well as diseased tissues (aka inflammation and cancer). During tumorigenesis, for instance, niche factors often become dispensable leading to a less stringent culture condition for cancer organoids as compared to healthy normal organoids. Established cancer organoids can be xenotransplanted to recapitulate histopathology of the parental tumor from which they are derived. Cancer organoids have been shown to reflect genetic lesions and gene expression patterns, opening up a possibility of in vitro drug testing for the prediction of clinical treatment response in patients.
Thus, biobanking of organoids derived from diseased tissues will help to unravel the pathogenesis of disease and the development of new diagnostic tools and new drugs. Our institute is currently setting up such a biobank for colon tissues from healthy, IBD and cancer patients.
Production scientifique scientific production
Rubio A*, Nai A*, Campanella A, Gourbeyre O, Artuso I, Bordini J, Gineste A, Latour C, Besson-Fournier C, Lin HY, Coppin H, Roth MP, Camaschella C, Silvestri L, Meynard D.Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice.
Blood. 2016 May 12;127(19):2327-36.
Ghossoub R, Lembo F, Rubio A, Gaillard CB, Bouchet J, Vitale N, Slavík J, Machala M, Zimmermann P.
Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2.
Nat Commun. 2014 Mar 18;5:3477
*co-premier auteur
Blood. 2016 May 12;127(19):2327-36.
Ghossoub R, Lembo F, Rubio A, Gaillard CB, Bouchet J, Vitale N, Slavík J, Machala M, Zimmermann P.
Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2.
Nat Commun. 2014 Mar 18;5:3477
*co-premier auteur
