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Kidney regeneration by xeno-embryonic nephrogenesis

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Abstract

Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.

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References

  1. Locatelli F, Vecchio LD, Possoni P, Monzoni C (2006) Nephrology: main advances in the last 40 years. J Nephrol 19:6–11

    PubMed  Google Scholar 

  2. Fung J (2004) Tacrolimus and transplantation: a decade in review. Transplantation 77:S41–S43

    Article  PubMed  CAS  Google Scholar 

  3. Thadhani R, Pascual M, Bonventre JV (1996) Medical progress: acute renal failure. N Engl J Med 334:1448–1460

    Article  PubMed  CAS  Google Scholar 

  4. Woolf AS, Palmer SJ, Snow ML, Fine LG (1990) Creation of functioning chimeric mammalian kidney. Kidney Int 38:991–997

    Article  PubMed  CAS  Google Scholar 

  5. Rogers S, Lowell JA, Hammerman NA, Hammerman MR (1998) Transplantation of developing metanephroi into adult rats. Kidney Int 54:27–37

    Article  PubMed  CAS  Google Scholar 

  6. Hammerman MR (2003) Tissue engineering the kidney. Kidney Int 63:1195–1204

    Article  PubMed  Google Scholar 

  7. Chan T, Ariizumi T, Asashima M (1999) A model system for organ engineering: transplantation of in vitro induced embryonic kidney. Naturwissenschaften 86:224–227

    Article  PubMed  CAS  Google Scholar 

  8. Lanza RP, Chuug HY, Yoo JJ, Wettestein PJ, Blackwell C, Borson N, Hofmeister E, Schuch G, Soker S, Moraes CT, West MD, Atala A (2002) Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol 20:689–696

    Article  PubMed  CAS  Google Scholar 

  9. Osafune K, Takasato M, Kispert A, Asashima M, Nishinakamura R (2005) Identification of multipotent progenitors in the embryonic mouse kidney by a novel colony-forming assay. Development (Camb) 133:151–161

    Article  CAS  Google Scholar 

  10. Saxen L, Sariola H (1987) Early organogenesis of the kidney. Pediatr Nephrol 1:385–392

    Article  PubMed  CAS  Google Scholar 

  11. Davies JA, Fisher CE (2002) Genes and protein in renal development. Exp Nephrol 10:102–113

    Article  PubMed  CAS  Google Scholar 

  12. Lipschuts JH (1998) Molecular development of the kidney: a review of the results of gene disruption studies. Am J Kidney Dis 31:383–397

    Article  Google Scholar 

  13. Yokoo T, Ohashi T, Shen J-S, Sakurai K, Miyazaki Y, Utsunomiya Y, Takahashi M, Terada Y, Eto Y, Kawamura T, Osumi N, Hosoya T (2005) Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissue. Proc Natl Acad Sci U S A 102:3296–3300

    Article  PubMed  CAS  Google Scholar 

  14. Abrahamson DR, Robert B, Hyink DP, St. John PL, Daniel TO (1998) Origins and formation of microvasculature in the developing kidney. Kidney Int 54(suppl 67):S-7–S-11

    Google Scholar 

  15. Rogers SA, Powell-Braxton L, Hammerman MR (1999) Insulin-like growth factor I regulates renal development in rodents. Dev Genet 24:293

    Article  PubMed  CAS  Google Scholar 

  16. Rogers SA, Liapis H, Hammerman MR (2001) Transplantation of metanephroi across the major histocompatibility complex in rats. Am J Physiol Regul Integr Comp Physiol 280:R132

    PubMed  CAS  Google Scholar 

  17. Rogers SA, Hammerman MR (2001) Transplantation of metanephroi after preservation in vitro. Am J Physiol Regul Integr Comp Physiol 281:R661

    PubMed  CAS  Google Scholar 

  18. Yokoo T, Fukui A, Ohashi T, Miyazaki Y, Utsunomiya Y, Kawamura T, Hosoya T, Okabe M, Kobayashi E (2006) Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo. J Am Soc Nephrol 17:1026–1034

    Article  PubMed  Google Scholar 

  19. Inoue H, Osawa I, Murakami T, Kimura A, Hakamata Y, Sato Y, Kaneko T, Okada T, Ozawa K, Francis J, Lione P, Kobayashi E (2005) Development of new inbred transgenic strains of rats with LacZ or GFP. Biochem Biophys Res Commun 329:288–295

    Article  PubMed  CAS  Google Scholar 

  20. Marshall D, Clancy M, Bottomley M, Symonds K, Brenchley PEC, Bravery CA (2005) Transplantation of metanephroi to sites within the abdominal cavity. Transplant Proc 37:194–197

    Article  PubMed  CAS  Google Scholar 

  21. Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med 316:73–78

    PubMed  CAS  Google Scholar 

  22. Erslev AJ, Besarab A (1997) Erythropoietin in the pathogenesis and treatment of the anemia of chronic renal failure. Kidney Int 51:622–630

    Article  PubMed  CAS  Google Scholar 

  23. Tsakiris D (2000) Morbidity and mortality reduction associated with the use of erythropoietin. Nephron 85(suppl 1):S2–S8

    Article  Google Scholar 

  24. Eckardt K-U (2001) After 15 years of success: perspectives of erythropoietin therapy. Nephrol Dial Transplant 16:1745–1749

    Article  PubMed  CAS  Google Scholar 

  25. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    Article  PubMed  CAS  Google Scholar 

  26. Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Whalestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A 99:2344–2349

    Article  PubMed  CAS  Google Scholar 

  27. Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St-Onge L, Wobus AM (2003) Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci U S A 100:998–1003

    Article  PubMed  CAS  Google Scholar 

  28. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18:399–404

    Article  PubMed  CAS  Google Scholar 

  29. Thomson JA, Etskovitz-Eldor J, Shapiro SS, Wakniz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines from human blastocysts. Science 282:1145–1147

    Article  PubMed  CAS  Google Scholar 

  30. Schuldiner M, Yanuka O, Itskovitz-Ekdor J, Melton DA, Benvenisty N (2000) Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 97:11307–11312

    Article  PubMed  CAS  Google Scholar 

  31. Kobayashi T, Tanaka H, Kuwana H, Inoshita S, Teraoka H, Sasaki S, Terada Y (2005) Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells. Biochem Biophys Res Commun 336:585–595

    Article  PubMed  CAS  Google Scholar 

  32. Steenhard BM, Isom KS, Cazcarro P, Dunmore JH, Godwin AR, St. John PL, Abrahamson DA (2005) Integration of embryonic stem cells in metanephric kidney organ culture. J Am Soc Nephrol 16:1623–1631

    Article  PubMed  CAS  Google Scholar 

  33. Kim D, Dressler G (2005) Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia. J Am Soc Nephrol 16:3527–3534

    Article  PubMed  CAS  Google Scholar 

  34. Vigneau C, Polgar K, Striker G, Elliott J, Hyink D, Weber O, Fehling H-J, Keller G, Burrow C, Wilson P (2007) Mouse embryonic stem cell-derived embryoid bodies generate progenitors that integrate long term into renal proximal tubules in vivo. J Am Soc Nephrol 18:1709–1720

    Article  PubMed  CAS  Google Scholar 

  35. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Cambell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature (Lond) 385:810–813

    Article  CAS  Google Scholar 

  36. Egli D, Rosains J, Birkhoff G, Eggan K (2007) Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature (Lond) 447:679–685

    Article  CAS  Google Scholar 

  37. Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, Koo JM, Jeon HY, Lee BC, Kang SK, Kim SJ, Ahn C, Hwang JH, Park KY, Cibelli JB, Moon SY (2004) Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 303:1669–1674. [Retraction in Kennedy D (2006) Science 311:335]

    Article  PubMed  CAS  Google Scholar 

  38. Byrne JA, Pedersen DA, Clepper LL, Melson M, Sanger WG, Gokhale S, Wolf DP, Mitalipov SM (2007) Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature (Lond) 450:497–502

    Article  CAS  Google Scholar 

  39. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  PubMed  CAS  Google Scholar 

  40. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature (Lond) 448: 313–317

    Article  CAS  Google Scholar 

  41. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature (Lond) 448:318–324

    Article  CAS  Google Scholar 

  42. Meissner A, Wernig M, Jaenisch R (2007) Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol 25:1177–1181

    Article  PubMed  CAS  Google Scholar 

  43. Hanna J, Wernig M, Markoulaki S, Sun C-W, Meissner A, Cassady JP, Beard C, Brambrink T, Wu L-C, Townes TM, Jaenisch R (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318(5858):1920–1923

    Article  PubMed  CAS  Google Scholar 

  44. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:1–12

    Article  CAS  Google Scholar 

  45. Pereira RF, Halford KW, O’Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ (1995) Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A 92:4857–4861

    Article  PubMed  CAS  Google Scholar 

  46. Pereira RF, O’Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ (1998) Marrow stromal cells as a source of progenitor cells for non-hematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci U S A 95:1142–1147

    Article  PubMed  CAS  Google Scholar 

  47. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286

    Article  PubMed  CAS  Google Scholar 

  48. Bussolati B, Camussi G (2007) Stem cells in acute kidney injury. Contrib Nephrol 156:250–258

    Article  PubMed  Google Scholar 

  49. Kunter U, Rong S, Boor P, Eitner F, Muller-Newen G, Djuric Z, van Roeyen CR, Konieczny A, Ostendorf T, Villa L, Milovanceva-Popovska M, Kerjaschki D, Floege J (2007) Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J Am Soc Nephrol 18: 1754–1764

    Article  PubMed  CAS  Google Scholar 

  50. Prockop DJ (1997) Marrow stromal cells as stem cells for non-hematopoietic tissues. Science 276:71–74

    Article  PubMed  CAS  Google Scholar 

  51. Yamamoto M, Cui L, Johkura K, Asanuma K, Okouchi Y, Ogiwara N, Sasaki K (2005) Branching ducts similar to mesonephric ducts or ureteric buds in teratomas originating from mouse embryonic stem cells. Am J Physiol Renal Physiol 290:F52–F60

    Article  PubMed  CAS  Google Scholar 

  52. Saxen L, Sariola H (1987) Early organogenesis of the kidney. Pediatr Nephrol 1:385–392

    Article  PubMed  CAS  Google Scholar 

  53. Davies JA (2002) Morphogenesis of the metanephric kidney. Sci World J 2:1937–1950

    Google Scholar 

  54. Hannema SE, Hughew IA (2007) Regulation of Wolffian duct development. Horm Res 67:142–151

    Article  PubMed  CAS  Google Scholar 

  55. Costantini F (2006) Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation (Camb) 74:402–421

    Article  CAS  Google Scholar 

  56. Smith HW (1943) Evolution of the kidney. In: Lectures on the kidney. University of Kansas Press, Kansas City, pp 1–23

    Google Scholar 

  57. Fraser EA (1950) The development of the vertebrate excretory system. Biol Rev 25:159–187

    Article  Google Scholar 

  58. Nishimura H, Koseki C, Patel TB (1996) Water transport in collecting ducts of Japanese quail. Am J Physiol 271:R1535–R1543

    PubMed  CAS  Google Scholar 

  59. Sokabe H, Ogawa M, Oguri M, Nishimura H (1969) Evolution of the juxtaglomerular apparatus in the vertebrate kidneys. Tex Rep Biol Med 27(3):867–885

    PubMed  CAS  Google Scholar 

  60. Obara-Ishihara T, Kuhlman J, Niswander L, Herzlinger D (1999) The surface ectoderm is essential for nephric duct formation in intermediate mesoderm. Development (Camb) 126:1103–1108

    CAS  Google Scholar 

  61. Hammerman MR (2004) Renal organogenesis from transplanted metanephric primordia. J Am Soc Nephrol 15:1126–1132

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishishimbashi Minato-ku, Tokyo, 105-8461, Japan

    Takashi Yokoo, Akira Fukui, Kei Matsumoto & Tetsuya Kawamura

Authors
  1. Takashi Yokoo
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  2. Akira Fukui
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  3. Kei Matsumoto
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  4. Tetsuya Kawamura
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Correspondence to Takashi Yokoo.

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Yokoo, T., Fukui, A., Matsumoto, K. et al. Kidney regeneration by xeno-embryonic nephrogenesis. Med Mol Morphol 41, 5–13 (2008). https://doi.org/10.1007/s00795-008-0396-9

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