Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells

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 three-dimensional microenvironment, and by applying defined renal inductive signals, we generated kidney organoids...

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Bibliographic Details
Authors: Garreta, Elena, Prado, Patricia, Tarantino, Carolina, Oria, Roger, Fanlo, Lucía, Martí, Elisa, Zalvidea, Dobryna, Trepat Guixer, Xavier, Roca-Cusachs Soulere, Pere, Gavaldà i Navarro, Aleix, Cozzuto, Luca, Campistol Plana, Josep M., Izpisúa Belmonte, Juan Carlos, Hurtado del Pozo, Carmen, Montserrat, Núria
Format: article
Status:Versión aceptada para publicación
Publication Date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/159622
Online Access:https://hdl.handle.net/2445/159622
Access Level:Open access
Keyword:Medicina regenerativa
Cèl·lules mare
Regenerative medicine
Stem cells
Description
Summary: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 three-dimensional 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.

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