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Engineering human pluripotent stem cells to model tissue development and disease
The generation of human pluripotent stem cells (hPSCs) derived organoids is one of the biggest scientific advances in regenerative medicine. Recently, we have demonstrated that by lengthening the time that hPSCs are exposed to a three-dimensional microenvironment in the presence of defined renal inductive signals we are able to generate kidney organoids that transcriptomically match second-trimester human fetal kidneys. Furthermore, we have developed a transplantation method that exploits the intrinsic properties of the chick chorioallantoic membrane (CAM) to recreate a soft in vivo microenvironment for organoid growth and differentiation, including vascularization in vivo. Now we are exploiting our kidney organoid culture platforms to assess kidney disease modeling and the study of kidney morphogenesis. Towards this aim we will explain on the derivation of hPSCs for the inducible expression of Cas9 allowing for targeted genome editing at both pluripotent stage and during kidney organoid generation. Furthermore, we will also discuss on several applications that include the amenability of kidney organoids for COVID19 research applications.