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Title

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

AuthorsGarreta, Elena; Prado, Patricia ; Tarantino, Carolina; Oria, Roger; Fanlo, Lucía ; Martí, Elisa ; Zalvidea, Dobryna; Trepat, Xavier; Roca-Cusachs, Pere; Gavaldà-Navarro, Aleix; Cozzuto, Luca; Campistol, Josep M.; Izpisúa Belmonte, Juan Carlos; Hurtado del Pozo, Carmen ; Montserrat, Núria
KeywordsBiomaterials
Biomaterials – cells
Embryonic stem cells
Pluripotent stem cells
Stem cells
Issue DateApr-2019
PublisherSpringer Nature
CitationNature Materials 18: 397-405 (2019)
AbstractThe 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.
Publisher version (URL)http://dx.doi.org/10.1038/s41563-019-0287-6
URIhttp://hdl.handle.net/10261/201494
DOI10.1038/s41563-019-0287-6
ISSN1476-1122
E-ISSN1476-4660
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