Extended Data Fig. 10. IT-603 attenuates fibrosis in ex vivo human tissues slice models of liver and kidney fibrosis.

(a) Diagrams show the experimental timelines of TGF(1 induced fibrosis in ex vivo normal human liver and kidney precision cut slices (PCS). (b) Representative images of CD68 stained liver and kidney tissue slices. (c) Representative images and histological quantification of Picrosirius red stained fibrotic kidney slices ± IT-603 therapy (p<0.0001). Representative images and histological quantification of αSMA stained fibrotic kidney slices ± IT-603 therapy (p<0.0001). Red line denotes the value for the T=0 slice. (e) Quantification of soluble collagen released from fibrotic kidney slices ± IT-603 therapy (p=0.0015). (f) Quantification of the neo-epitope pro C3 released from fibrotic kidney slices ± IT-603 therapy (p=0.0493). (g) Graph showing average LDH release in the media expressed as a percentage (%) of positive control (LDH levels in media from a PCS where maximal death was induced by multiple freeze/thaws – normalized to media volume). (IT-603 p=0.023 and IT-603+TGFβ1 p=0.02). Images representative of n=3 independent slice experiments. Data are mean ± s.e.m. and representative of slices generated from 3 independent donors performed in duplicate. Scale bars equal 100 microns. P values were calculated using two-way ANOVA with Tukey post- hoc t-test (*P<0.05, **P<0.01, ***P<0.001 and ****P<0.0001).