Generation of functional podocytes from human induced pluripotent stem cells

Osele Ciampi, Roberto Iacone, Lorena Longaretti, Valentina Benedetti, Martin Graf, Maria Chiara Magnone, Christoph Patsch, Christodoulos Xinaris, Giuseppe Remuzzi, Ariela Benigni, Susanna Tomasoni

Research output: Contribution to journalArticle

Abstract

Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

Original languageEnglish
Pages (from-to)130-139
Number of pages10
JournalStem Cell Research
Volume17
Issue number1
DOIs
Publication statusPublished - Jul 1 2016

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Keywords

  • Differentiation
  • Induced pluripotent stem cells
  • Nephron progenitors
  • Podocytes

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Ciampi, O., Iacone, R., Longaretti, L., Benedetti, V., Graf, M., Magnone, M. C., Patsch, C., Xinaris, C., Remuzzi, G., Benigni, A., & Tomasoni, S. (2016). Generation of functional podocytes from human induced pluripotent stem cells. Stem Cell Research, 17(1), 130-139. https://doi.org/10.1016/j.scr.2016.06.001