While SARS-CoV-2 primarily targets the respiratory system, studies have shown that it also infects and multiplies within the intestinal epithelium. IPSC-derived organoids exhibit characteristics that closely mimic the in vivo intestinal epithelium, making them a valuable surrogate model for studying the virus.
DefiniGEN iPSC-derived intestinal organoids provide a unique in vitro system to model the human intestine. The organoids display a polarized epithelium and harbor a mixture of cell types normally present in the primary intestinal epithelium barrier in vivo, including goblet cells, Paneth cells, enterocytes, LRG5+ stem cells, and enteroendocrine cells. The organoids polarize, form crypt structures and grow villi at the apical surface, and are shown to secrete mucus in a similar manner to primary human gut tissue.
Figure 1. Gene expression in Def-INT cells of ACE2 a key protein required for SARS-CoV-2 infection.
Figure 2. Gene expression in Def-INT cells of TMPRSS2 a key protein required for SARS-CoV-2 infection.
There is growing evidence that ethnic differences are a major factor in patients showing a severe response to Covid19. We have a platform to generate various patient-derived intestinal models which could support population studies, using many different donors with diverse ethnic profiles.
DefiniGEN’s differentiation platform is optimized to enable successful generation of intestinal organoids from a diverse range of patients. Patient skin fibroblasts or PBMCs can first be reprogrammed to iPSC, and then differentiated to produce mature intestinal organoids which carry the original patient genetics, and so manifest a gut model specific to that donor.
Studies have found significant differences exist between donors in their capacity to generate endodermal human cells via iPSC, however DefiniGEN's platform offers a much higher success rate in producing good quality mature and biologically representative organoids. We titrate a number of differentiation parameters at a small scale to establish the best conditions for downstream cell production, which helps control for the usual heterogeneity in successful differentiation and allows us to work with diverse cohorts of patients with reproducible success.