title: Urine excretion strategy for stem cell-generated embryonic kidneys.
abstract: There have been several recent attempts to generate, de novo, a functional whole kidney from stem cells using the organogenic niche or blastocyst complementation methods. However, none of these attempts succeeded in constructing a urinary excretion pathway for the stem cell-generated embryonic kidney. First, we transplanted metanephroi from cloned pig fetuses into gilts; the metanephroi grew to about 3 cm and produced urine, although hydronephrosis eventually was observed because of the lack of an excretion pathway. Second, we demonstrated the construction of urine excretion pathways in rats. Rat metanephroi or metanephroi with bladders (developed from cloacas) were transplanted into host rats. Histopathologic analysis showed that tubular lumina dilation and interstitial fibrosis were reduced in kidneys developed from cloacal transplants compared with metanephroi transplantation. Then we connected the host animal's ureter to the cloacal-developed bladder, a technique we called the "stepwise peristaltic ureter" (SWPU) system. The application of the SWPU system avoided hydronephrosis and permitted the cloacas to differentiate well, with cloacal urine being excreted persistently through the recipient ureter. Finally, we demonstrated a viable preclinical application of the SWPU system in cloned pigs. The SWPU system also inhibited hydronephrosis in the pig study. To our knowledge, this is the first report showing that the SWPU system may resolve two important problems in the generation of kidneys from stem cells: construction of a urine excretion pathway and continued growth of the newly generated kidney.
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan;
authors.forename: Shinya
authors.initials: S
authors.lastname: Yokote
authors.affiliation: Meiji University International Institute for Bio-Resource Research, Kawasaki 214-8571, Japan; Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan;
authors.forename: Hitomi
authors.initials: H
authors.lastname: Matsunari
authors.affiliation: Laboratory of Small Animal Surgery I, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Japan;
authors.forename: Satomi
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan; Division of Regenerative Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan;
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Yamanaka
authors.affiliation: Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan;
authors.forename: Ayuko
authors.initials: A
authors.lastname: Uchikura
authors.affiliation: Division of Regenerative Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan; Department of Urology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan;
authors.forename: Eisuke
authors.initials: E
authors.lastname: Fujimoto
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan;
authors.forename: Kei
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Meiji University International Institute for Bio-Resource Research, Kawasaki 214-8571, Japan; Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Department of Organ Fabrication, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan; tyokoo@jikei.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoo
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology*; D007668:Kidney / Q000196:embryology / Q000502:physiology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D014556:Urine
keywords: cloned pig; kidney generation; metanephros; somatic cell nuclear transfer; transplantation