Skip to main content

Abstract

The word “Organogenesis” is defined as “the production and development of the organs of an animal or plant” [1]. In the context of medical research, it has traditionally been applied to the natural processes of fetal development but it is now beginning to be applied also to the creation of living organs, or organ substitutes, by artificial means. It is this latter meaning that is most relevant to this book and most of this chapter will therefore focus on artificial organogenesis. It will be helpful, though, to review the basic features of natural organogenesis first, because the most successful methods of artificial organogenesis tend to build on them.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. The New Oxford Dictionary of English (1998) Oxford University Press, Oxford

    Google Scholar 

  2. Grobstein C (1953) Inductive epitheliomesenchymal interaction in cultured organ rudiments of the mouse. Science 118(3054):52–55

    Article  PubMed  CAS  Google Scholar 

  3. Little MH, Brennan J, Georgas K, Davies JA, Davidson DR, Baldock RA, et al. (2007) A high-resolution anatomical ontology of the developing murine genitourinary tract. Gene Expr Patterns 7(6):680–699

    Article  PubMed  CAS  Google Scholar 

  4. Alarid ET, Rubin JS, Young P, Chedid M, Ron D, Aaronson SA, et al. (1994) Keratinocyte growth factor functions in epithelial induction during seminal vesicle development. Proc Natl Acad Sci U S A 91(3):1074–1078

    Article  PubMed  CAS  Google Scholar 

  5. Morita K, Nogawa H (1999) EGF-dependent lobule formation and FGF7-dependent stalk elongation in branching morphogenesis of mouse salivary epithelium in vitro. Dev Dyn 215(2):148–154

    Article  PubMed  CAS  Google Scholar 

  6. Thomson AA (2001) Role of androgens and fibroblast growth factors in prostatic development. Reproduction 121(2):187–195

    Article  PubMed  CAS  Google Scholar 

  7. Sugimura Y, Foster BA, Hom YK, Lipschutz JH, Rubin JS, Finch PW, et al. (1996) Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate. Int J Dev Biol 40(5):941–951

    PubMed  CAS  Google Scholar 

  8. Bellusci S, Grindley J, Emoto H, Itoh N, Hogan BL (1997) Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development 124(23):4867–4878

    PubMed  CAS  Google Scholar 

  9. Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, et al. (2000) FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun 277(3):643–649

    Article  PubMed  CAS  Google Scholar 

  10. Makarenkova HP, Ito M, Govindarajan V, Faber SC, Sun L, McMahon G, et al. (2000) FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development 127(12):2563–2572

    PubMed  CAS  Google Scholar 

  11. Bates CM (2007) Role of fibroblast growth factor receptor signaling in kidney development. Pediatr Nephrol 22(3):343–349

    Article  PubMed  Google Scholar 

  12. Sainio K, Suvanto P, Davies J, Wartiovaara J, Wartiovaara K, Saarma M, et al. (1997) Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 124(20):4077–4087

    PubMed  CAS  Google Scholar 

  13. Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367(6461):380–383

    Article  PubMed  CAS  Google Scholar 

  14. Schuchardt A, D’Agati V, Pachnis V, Costantini F (1996) Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development. Development 122(6):1919–1929

    PubMed  CAS  Google Scholar 

  15. Dean CH, Miller LA, Smith AN, Dufort D, Lang RA, Niswander LA (2005) Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland. Dev Biol 286(1):270–286

    Article  PubMed  CAS  Google Scholar 

  16. Merkel CE, Karner CM, Carroll TJ (2007) Molecular regulation of kidney development: is the answer blowing in the Wnt? Pediatr Nephrol 22(11):1825–1838

    Article  PubMed  Google Scholar 

  17. Michos O, Goncalves A, Lopez-Rios J, Tiecke E, Naillat F, Beier K, et al. (2007) Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development 134(13):2397–2405

    Article  PubMed  CAS  Google Scholar 

  18. Ritvos O, Tuuri T, Eramaa M, Sainio K, Hilden K, Saxen L, et al. (1995) Activin disrupts epithelial branching morphogenesis in developing glandular organs of the mouse. Mech Dev 50(2–3):229–245

    Article  PubMed  CAS  Google Scholar 

  19. Dean C, Ito M, Makarenkova HP, Faber SC, Lang RA (2004) Bmp7 regulates branching morphogenesis of the lacrimal gland by promoting mesenchymal proliferation and condensation. Development 131(17):4155–4165

    Article  PubMed  CAS  Google Scholar 

  20. Bellusci S, Furuta Y, Rush MG, Henderson R, Winnier G, Hogan BL (1997) Involvement of sonic hedgehog (shh) in mouse embryonic lung growth and morphogenesis. Development 124(1):53–63

    PubMed  CAS  Google Scholar 

  21. Yu J, Carroll TJ, McMahon AP (2002) Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney. Development 129(22):5301–5312

    PubMed  CAS  Google Scholar 

  22. Pepicelli CV, Lewis PM, McMahon AP (1998) Sonic hedgehog regulates branching morphogenesis in the mammalian lung. Curr Biol 8(19):1083–1086

    Article  PubMed  CAS  Google Scholar 

  23. Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell 9(2):283–292

    Article  PubMed  CAS  Google Scholar 

  24. Karavanova ID, Dove LF, Resau JH, Perantoni AO (1996) Conditioned medium from a rat ureteric bud cell line in combination with bFGF induces complete differentiation of isolated metanephric mesenchyme. Development 122(12):4159–4167

    PubMed  CAS  Google Scholar 

  25. Stabellini G, Calvitti M, Becchetti E, Carinci P, Calastrini C, Lilli C, et al. (2007) Lung regions differently modulate bronchial branching development and extracellular matrix plays a role in regulating the development of chick embryo whole lung. Eur J Histochem 51(1):33–42

    PubMed  CAS  Google Scholar 

  26. Sakai T, Larsen M, Yamada KM (2003) Fibronectin requirement in branching morphogenesis. Nature 423(6942):876–881

    Article  PubMed  CAS  Google Scholar 

  27. Ye P, Habib SL, Ricono JM, Kim NH, Choudhury GG, Barnes JL, et al. (2004) Fibronectin induces ureteric bud cells branching and cellular cord and tubule formation. Kidney Int 66(4):1356–1364

    Article  PubMed  CAS  Google Scholar 

  28. Larsen M, Wei C, Yamada KM (2006) Cell and fibronectin dynamics during branching morphogenesis. J Cell Sci 119(Pt 16):3376–3384

    Article  PubMed  CAS  Google Scholar 

  29. Nakanishi Y, Ishii T (1989) Epithelial shape change in mouse embryonic submandibular gland: modulation by extracellular matrix components. Bioessays 11(6):163–167

    Article  PubMed  CAS  Google Scholar 

  30. Zent R, Bush KT, Pohl ML, Quaranta V, Koshikawa N, Wang Z, et al. (2001) Involvement of laminin binding integrins and laminin-5 in branching morphogenesis of the ureteric bud during kidney development. Dev Biol 238(2):289–302

    Article  PubMed  CAS  Google Scholar 

  31. Brandenberger R, Schmidt A, Linton J, Wang D, Backus C, Denda S, et al. (2001) Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin alpha8beta1 in the embryonic kidney. J Cell Biol 154(2):447–458

    Article  PubMed  CAS  Google Scholar 

  32. Wang R, Li J, Lyte K, Yashpal NK, Fellows F, Goodyer CG (2005) Role for beta1 integrin and its associated alpha3, alpha5, and alpha6 subunits in development of the human fetal pancreas. Diabetes 54(7):2080–2089

    Article  PubMed  CAS  Google Scholar 

  33. Gill SE, Pape MC, Leco KJ (2006) Tissue inhibitor of metalloproteinases 3 regulates extracellular matrix—cell signaling during bronchiole branching morphogenesis. Dev Biol 298(2):540–554

    Article  PubMed  CAS  Google Scholar 

  34. Davies J (2005) Mechanisms of morphogenesis. Academic Press, Oxford

    Google Scholar 

  35. Sakurai H, Barros EJ, Tsukamoto T, Barasch J, Nigam SK (1997) An in vitro tubulogenesis system using cell lines derived from the embryonic kidney shows dependence on multiple soluble growth factors. Proc Natl Acad Sci U S A 94(12):6279–6284

    Article  PubMed  CAS  Google Scholar 

  36. Wei C, Larsen M, Hoffman MP, Yamada KM (2007) Self-organization and branching morphogenesis of primary salivary epithelial cells. Tissue Eng 13(4):721–735

    Article  PubMed  CAS  Google Scholar 

  37. Soriano JV, Pepper MS, Nakamura T, Orci L, Montesano R (1995) Hepatocyte growth factor stimulates extensive development of branching duct-like structures by cloned mammary gland epithelial cells. J Cell Sci 108 (Pt 2):413–430

    PubMed  CAS  Google Scholar 

  38. Schuger L, O’Shea KS, Nelson BB, Varani J (1990) Organotypic arrangement of mouse embryonic lung cells on a basement membrane extract: involvement of laminin. Development 110(4):1091–1099

    PubMed  CAS  Google Scholar 

  39. Preminger GM, Koch WE, Fried FA, Mandell J (1980) Utilization of the chick chorioallantoic membrane for in vitro growth of the embryonic murine kidney. Am J Anat 159(1):17–24

    Article  PubMed  CAS  Google Scholar 

  40. Woolf AS, Palmer SJ, Snow ML, Fine LG (1990) Creation of a functioning chimeric mammalian kidney. Kidney Int 38(5):991–997

    Article  PubMed  CAS  Google Scholar 

  41. Tufro A (2000) VEGF spatially directs angiogenesis during metanephric development in vitro. Dev Biol 227(2):558–566

    Article  PubMed  CAS  Google Scholar 

  42. Sariola H, Ekblom P, Lehtonen E, Saxen L (1983) Differentiation and vascularization of the metanephric kidney grafted on the chorioallantoic membrane. Dev Biol 96(2):427–435

    Article  PubMed  CAS  Google Scholar 

  43. Eckardt KU (1996) Erythropoietin production in liver and kidneys. Curr Opin Nephrol Hypertens 5(1):28–34

    PubMed  CAS  Google Scholar 

  44. Della BR, Kurtz A, Schricker K (1996) Regulation of renin synthesis in the juxtaglomerular cells. Curr Opin Nephrol Hypertens 5(1):16–19

    Google Scholar 

  45. Humes HD, Fissell WH, Weitzel WF, Buffington DA, Westover AJ, MacKay SM, et al. (2002) Metabolic replacement of kidney function in uremic animals with a bioartificial kidney containing human cells. Am J Kidney Dis 39(5):1078–1087

    Article  PubMed  Google Scholar 

  46. Tiranathanagul K, Brodie J, Humes HD (2006) Bioartificial kidney in the treatment of acute renal failure associated with sepsis. Nephrology (Carlton ) 11(4):285–291

    Article  Google Scholar 

  47. Humes HD, Buffington DA, Lou L, Abrishami S, Wang M, Xia J, et al. (2003) Cell therapy with a tissue-engineered kidney reduces the multiple-organ consequences of septic shock. Crit Care Med 31(10):2421–2428

    Article  PubMed  CAS  Google Scholar 

  48. Kramer L, Gendo A, Madl C, Ferrara I, Funk G, Schenk P, et al. (2000) Biocompatibility of a cuprophane charcoal-based detoxification device in cirrhotic patients with hepatic encephalopathy. Am J Kidney Dis 36(6):1193–1200

    Article  PubMed  CAS  Google Scholar 

  49. Sauer IM, Neuhaus P, Gerlach JC (2002) Concept for modular extracorporeal liver support for the treatment of acute hepatic failure. Metab Brain Dis 17(4):477–484

    Article  PubMed  CAS  Google Scholar 

  50. Zeilinger K, Sauer IM, Pless G, Strobel C, Rudzitis J, Wang A, et al. (2002) Three-dimensional co-culture of primary human liver cells in bioreactors for in vitro drug studies: effects of the initial cell quality on the long-term maintenance of hepatocyte-specific functions. Altern Lab Anim 30(5):525–538

    PubMed  CAS  Google Scholar 

  51. Sauer IM, Zeilinger K, Obermayer N, Pless G, Grunwald A, Pascher A, et al. (2002) Primary human liver cells as source for modular extracorporeal liver support—a preliminary report. Int J Artif Organs 25(10):1001–1005

    PubMed  CAS  Google Scholar 

  52. Irgang M, Sauer IM, Karlas A, Zeilinger K, Gerlach JC, Kurth R, et al. (2003) Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. J Clin Virol 28(2):141–154

    Article  PubMed  CAS  Google Scholar 

  53. Dixit V, Gitnick G (1998) The bioartificial liver: state-of-the-art. Eur J Surg Suppl 164(582):71–76

    Google Scholar 

  54. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, et al. (2006) Generation of a functional mammary gland from a single stem cell. Nature 439(7072):84–88

    Article  PubMed  CAS  Google Scholar 

  55. Desbaillets I, Ziegler U, Groscurth P, Gassmann M (2000) Embryoid bodies: an in vitro model of mouse embryogenesis. Exp Physiol 85(6):645–651

    Article  PubMed  CAS  Google Scholar 

  56. Steenhard BM, Isom KS, Cazcarro P, Dunmore JH, Godwin AR, St John PL, et al. (2005) Integration of embryonic stem cells in metanephric kidney organ culture. J Am Soc Nephrol 16(6):1623–1631

    Article  PubMed  CAS  Google Scholar 

  57. Bruce SJ, Rea RW, Steptoe AL, Busslinger M, Bertram JF, Perkins AC (2007) In vitro differentiation of murine embryonic stem cells toward a renal lineage. Differentiation 75(5):337–349

    Article  PubMed  CAS  Google Scholar 

  58. Kim D, Dressler GR (2005) Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia. J Am Soc Nephrol 16(12):3527–3534

    Article  PubMed  CAS  Google Scholar 

  59. 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(2):585-595.

    Article  PubMed  CAS  Google Scholar 

  60. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302(5644):415–419

    Article  PubMed  CAS  Google Scholar 

  61. Lagasse E, Connors H, Al Dhalimy M, Reitsma M, Dohse M, Osborne L, et al. (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6(11):1229–1234

    Article  PubMed  CAS  Google Scholar 

  62. Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P (2003) Bone marrow stem cells regenerate infarcted myocardium. Pediatr Transplant 7(3):86–88

    Article  PubMed  Google Scholar 

  63. Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG (2003) Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest 112(1):42–49

    PubMed  CAS  Google Scholar 

  64. Lin F, Cordes K, Li L, Hood L, Couser WG, Shankland SJ, et al. (2003) Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol 14(5):1188–1199

    Article  PubMed  Google Scholar 

  65. Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T, et al. (2005) Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 115(7):1743–1755

    Article  PubMed  CAS  Google Scholar 

  66. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, et al. (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105(3):369–377

    Article  PubMed  CAS  Google Scholar 

  67. Lin F, Moran A, Igarashi P (2005) Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 115(7):1756–1764

    Article  PubMed  CAS  Google Scholar 

  68. Oliver JA, Maarouf O, Cheema FH, Martens TP, al Awqati Q (2004) The renal papilla is a niche for adult kidney stem cells. J Clin Invest 114(6):795–804

    PubMed  CAS  Google Scholar 

  69. Saito A, Kazama JJ, Iino N, Cho K, Sato N, Yamazaki H, et al. (2003) Bioengineered implantation of megalin-expressing cells: a potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure. J Am Soc Nephrol 14(8):2025–2032

    Article  PubMed  CAS  Google Scholar 

  70. Oberpenning F, Meng J, Yoo JJ, Atala A (1999) De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nat Biotechnol 17(2):149–155

    Article  PubMed  CAS  Google Scholar 

  71. Lanza RP, Chung HY, Yoo JJ, Wettstein PJ, Blackwell C, Borson N, et al. (2002) Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol 20(7):689–696

    Article  PubMed  CAS  Google Scholar 

  72. Hammerman MR (2003) Tissue engineering the kidney. Kidney Int 63(4):1195–1204

    Article  PubMed  Google Scholar 

  73. Rogers S, Hammerman M (2004) Prolongation of life in anephric rats following de novo renal organogenesis. Organogenesis 1(1):22–25

    Article  PubMed  Google Scholar 

  74. Rogers SA, Lowell JA, Hammerman NA, Hammerman MR (1998) Transplantation of developing metanephroi into adult rats. Kidney Int 54(1):27–37

    Article  PubMed  CAS  Google Scholar 

  75. Marshall D, Dilworth MR, Clancy M, Bravery CA, Ashton N (2007) Increasing renal mass improves survival in anephric rats following metanephros transplantation. Exp Physiol 92(1):263–271

    Article  PubMed  CAS  Google Scholar 

  76. Steer DL, Bush KT, Meyer TN, Schwesinger C, Nigam SK (2002) A strategy for in vitro propagation of rat nephrons. Kidney Int 62(6):1958–1965

    Article  PubMed  Google Scholar 

  77. Barasch J, Yang J, Ware CB, Taga T, Yoshida K, Erdjument-Bromage H, et al. (1999) Mesenchymal to epithelial conversion in rat metanephros is induced by LIF. Cell 99(4):377–386

    Article  PubMed  CAS  Google Scholar 

  78. Heinemann M, Panke S (2006) Synthetic biology—putting engineering into biology. Bioinformatics 22(22):2790–2799

    Article  PubMed  CAS  Google Scholar 

  79. Davies JA (2008) Synthetic morphology: prospects for engineered, self-constructing anatomies. J Anat 212(6):707-719.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Unbekandt, M., Davies, J. (2009). Control of Organogenesis: Towards Effective Tissue Engineering. In: Meyer, U., Handschel, J., Wiesmann, H., Meyer, T. (eds) Fundamentals of Tissue Engineering and Regenerative Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-77755-7_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-77755-7_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-77754-0

  • Online ISBN: 978-3-540-77755-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics