“Engineering human pluripotent stem cells for organoid applications in regenerative medicine”
Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain.
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain.
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 lengthening the time that hPSCs are exposed to a threedimensional microenvironment in the presence of defined renal inductive signals we are able to generate kidney organoids that transcriptomically match secondtrimester human fetal kidneys. Furthermore, we have recently developed a transplantation method that utilizes the chick chorioallantoic membrane to emulate a soft in vivo microenvironment further sustaining the growth and differentiation of implanted kidney organoids, as well as providing a vascular component.
In order to promote the efficient generation of nephron-like structures we have also mimicked the stiffness of the in ovo chorioallantoic membrane microenvironment in vitro by fabricating compliant hydrogels. This approach showed that by mirroring both biochemical and mechanical cues during organoid generation we are able to boost renal commitment and nephron differentiation. We will also discuss recent findings on the application of different bioengineering strategies (i.e., including 3D biopriting and tissue engineering) for kidney organoid generation, as well as the definition of culture conditions mimicking renal disease. Furthermore, we will discuss how through the use of CRISPR/Cas9 we are able to introduce mutations related to kidney developmental diseases exploiting kidney organoid technology.