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Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.

Publication ,  Journal Article
Musah, S; Mammoto, A; Ferrante, TC; Jeanty, SSF; Hirano-Kobayashi, M; Mammoto, T; Roberts, K; Chung, S; Novak, R; Ingram, M; Fatanat-Didar, T ...
Published in: Nature biomedical engineering
January 2017

An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications.

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Published In

Nature biomedical engineering

DOI

EISSN

2157-846X

ISSN

2157-846X

Publication Date

January 2017

Volume

1

Start / End Page

0069

Related Subject Headings

  • 4003 Biomedical engineering
 

Citation

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Musah, S., Mammoto, A., Ferrante, T. C., Jeanty, S. S. F., Hirano-Kobayashi, M., Mammoto, T., … Ingber, D. E. (2017). Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nature Biomedical Engineering, 1, 0069. https://doi.org/10.1038/s41551-017-0069
Musah, Samira, Akiko Mammoto, Thomas C. Ferrante, Sauveur S. F. Jeanty, Mariko Hirano-Kobayashi, Tadanori Mammoto, Kristen Roberts, et al. “Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.Nature Biomedical Engineering 1 (January 2017): 0069. https://doi.org/10.1038/s41551-017-0069.
Musah S, Mammoto A, Ferrante TC, Jeanty SSF, Hirano-Kobayashi M, Mammoto T, et al. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nature biomedical engineering. 2017 Jan;1:0069.
Musah, Samira, et al. “Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.Nature Biomedical Engineering, vol. 1, Jan. 2017, p. 0069. Epmc, doi:10.1038/s41551-017-0069.
Musah S, Mammoto A, Ferrante TC, Jeanty SSF, Hirano-Kobayashi M, Mammoto T, Roberts K, Chung S, Novak R, Ingram M, Fatanat-Didar T, Koshy S, Weaver JC, Church GM, Ingber DE. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nature biomedical engineering. 2017 Jan;1:0069.

Published In

Nature biomedical engineering

DOI

EISSN

2157-846X

ISSN

2157-846X

Publication Date

January 2017

Volume

1

Start / End Page

0069

Related Subject Headings

  • 4003 Biomedical engineering