The generation of organoids is one of the biggest scientific advances in regenerative medicine. Here, by lengthening the time that human pluripotent stem cells (hPSCs) were exposed to a threedimensional microenvironment, and by applying defined renal inductive signals, we generated kidney organoids that transcriptomically matched second-trimester human fetal kidneys. We validated these results using ex vivo and in vitro assays that model renal development. Furthermore, we developed a transplantation method that utilizes the chick chorioallantoic membrane. This approach created a soft in vivo microenvironment that promoted the growth and differentiation of implanted kidney organoids, as well as providing a vascular component. The stiffness of the in ovo chorioallantoic membrane microenvironment was recapitulated in vitro by fabricating compliant hydrogels. These biomaterials promoted the efficient generation of renal vesicles and nephron structures, demonstrating that a soft environment accelerates the differentiation of hPSC-derived kidney organoids. This work has recieved the prestigious award Íñigo Álvarez de Toledo in Basic Nephrology 2019. It has also been highlighted as a News and Views in the same journal Nature Materials and as an Editorial Comment in the prestigious journal Nature Reviews in Nephrology.
Reference
Garreta E, Prado P, Tarantino C, Oria R, Fanlo L, Martí E, Zalvidea D, Trepat X, Roca-Cusachs P, Gavaldà-Navarro A, Cozzuto L, Campistol JM, Izpisua Belmonte JC, Hurtado del Pozo C & Montserrat N 2019, ‘Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells.’ Nature Materials volume18, pages397–405.
Highlighted as Editor’s comment and News and Views in:
Allison SJ. A materials approach for kidney organoids. Nat Rev Nephrol. 2019 Mar 5. doi: 10.1038/s41581-019-0139-2
Chuva de Sousa Lopes SM. Accelerating maturation of kidney organoids. Nat Materials. 2019 Apr;18(4):303-304. doi: 10.1038/s41563-019-0326-3.
Kidney organoid generated from human pluripotent stem cells show complex architectural features as the presence of segmented nephron-like strucutres in only 16 days upon culture. For the first time the generated organoids transcriptomically resemble second trimester gestational human kidneys.
