title: Generation of kidney from pluripotent stem cells via blastocyst complementation.
abstract: Because a shortage of donor organs has been a major obstacle to the expansion of organ transplantation programs, the generation of transplantable organs is among the ultimate goals of regenerative medicine. However, the complex cellular interactions among and within tissues that are required for organogenesis are difficult to recapitulate in vitro. As an alternative, we used blastocyst complementation to generate pluripotent stem cell (PSC)-derived donor organs in vivo. We hypothesized that if we injected PSCs into blastocysts obtained from mutant mice in which the development of a certain organ was precluded by genetic manipulation, thereby leaving a niche for organ development, the PSC-derived cells would developmentally compensate for the defect and form the missing organ. In our previous work, we showed proof-of-principle findings of pancreas generation by injection of PSCs into pancreas-deficient Pdx1(-/-) mouse blastocysts. In this study, we have extended this technique to kidney generation using Sall1(-/-) mouse blastocysts. As a result, the defective cells were totally replaced, and the kidneys were entirely formed by the injected mouse PSC-derived cells, except for structures not under the influence of Sall1 expression (ie, collecting ducts and microvasculature). These findings indicate that blastocyst complementation can be extended to generate PSC-derived kidneys. This system may therefore provide novel insights into renal organogenesis.
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Jo-ichi
authors.initials: J
authors.lastname: Usui
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology; D005838:Genotype; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development*; D007678:Kidney Glomerulus / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008846:Micromanipulation / Q000379:methods; D009399:Nephrons / Q000166:cytology; D038081:Organogenesis / Q000502:physiology; D018183:Transplantation Chimera / Q000254:growth & development