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

Nat Mater. 2019 Apr;18(4):397-405. doi: 10.1038/s41563-019-0287-6. Epub 2019 Feb 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cellular Microenvironment
  • Extracellular Space / metabolism*
  • Female
  • Humans
  • Kidney / cytology*
  • Kinetics
  • Organoids / cytology*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Pregnancy
  • Pregnancy Trimester, Third
  • Tissue Culture Techniques / methods*
  • Transcriptome