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Nat Commun. 2019 Feb 5;10(1):451. doi: 10.1038/s41467-019-08394-9.

Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats.

Author information

1
Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, 444-8787, Aichi, Japan.
2
Center for Molecular Medicine, Jichi Medical University, Shimotsuke, 329-0498, Tochigi, Japan.
3
Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Minato-ku, 108-8639, Tokyo, Japan.
4
Faculty of Textile Science and Technology, Shinshu University, Ueda, 386-8567, Nagano, Japan.
5
The Graduate University of Advanced Studies, Okazaki, 444-8787, Aichi, Japan.
6
Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.
7
Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, 444-8787, Aichi, Japan. mhirarin@nips.ac.jp.
8
The Graduate University of Advanced Studies, Okazaki, 444-8787, Aichi, Japan. mhirarin@nips.ac.jp.

Abstract

Regeneration of human kidneys in animal models would help combat the severe shortage of donors in transplantation therapy. Previously, we demonstrated by interspecific blastocyst complementation between mouse and rats, generation of pluripotent stem cell (PSC)-derived functional pancreas, in apancreatic Pdx1 mutant mice. We, however, were unable to obtain rat PSC-derived kidneys in anephric Sall1 mutant mice, likely due to the poor contribution of rat PSCs to the mouse metanephric mesenchyme, a nephron progenitor. Here, conversely, we show that mouse PSCs can efficiently differentiate into the metanephric mesenchyme in rat, allowing the generation of mouse PSC-derived kidney in anephric Sall1 mutant rat. Glomerular epithelium and renal tubules in the kidneys are entirely composed of mouse PSC-derived cells expressing key functional markers. Importantly, the ureter-bladder junction is normally formed. These data provide proof-of-principle for interspecific blastocyst complementation as a viable approach for kidney generation.

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