Pediatric Surgery International

, Volume 26, Issue 6, pp 557–573 | Cite as

Tissue engineering and regenerative medicine research perspectives for pediatric surgery

  • Amulya K. SaxenaEmail author
Review Article


Tissue engineering and regenerative medicine research is being aggressively pursued in attempts to develop biological substitutes to replace lost tissue or organs. Remarkable degrees of success have been achieved in the generation of a variety of tissues and organs as a result of concerted contributions by multidisciplinary groups in the field of biotechnology. Engineering of an organ is a complex process which is initiated by appropriate sourcing of cells and their controlled proliferation to achieve critical numbers for seeding on biodegradable scaffolds in order to create cell-scaffold constructs, which are thereafter maintained in bioreactors to generate tissues identical to those required for replacement. Extensive efforts in understanding the characteristics of cells and their interaction with specifically tailored scaffolds holds the key to their attachment, controlled proliferation and differentiation, intercommunication, and organization to form tissues. The demand for tissue-engineered organs is enormous and this technology holds the promise to supply customized organs to overcome the severe shortages that are currently faced by the pediatric patient, especially due to organ-size mismatch. The contemporary state of tissue-engineering technology presented in this review summarizes the advances in the various areas of regenerative medicine and addresses issues that are associated with its future implementation in the pediatric surgical patient.


Tissue engineering Regenerative medicine Research Pediatric surgery 



Research funds from the European Union within the 6th Framework Program (EuroSTEC; LSHC-CT-2006-037409). Authors thank Symatese Biomateriaux, France and Matricel GmbH, Germany for scaffold images. The contributions of Prof. Michael E. Höllwarth, Mag. Kristina Kofler, Mrs. Anna Kuess, Mr. Herwig Ainoedhofer, Mr. Richard Ackbar, Dr. Piotr Soltysiak, Dr. Hinrich Baumgart, Dr. Christian Komann, Dr. Iris Wiederstein and Dr. Gerd Leitinger (Medical University of Graz, Austria) are gratefully appreciated.


  1. 1.
    Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926PubMedCrossRefGoogle Scholar
  2. 2.
    Lysaght MJ, O’Loughlin JA (2000) Demographic scope and economic magnitude of contemporary organ replacement therapies. ASAIO J 46:515–521PubMedCrossRefGoogle Scholar
  3. 3.
    Eurotransplant International Foundation Annual Report 2008. In: Oosterlee A, Rahmel A (eds) Eurotransplant International Foundation, Leiden, The Netherlands. ISBN-13: 978-90-71658-28-0Google Scholar
  4. 4.
    2008 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1998–2007. U.S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MDGoogle Scholar
  5. 5.
    Giovanelli M, Gupte GL, McKiernan P et al (2009) Impact of change in the United Kingdom pediatric donor organ allocation policy for intestinal transplantation. Transplantation 87:1695–1699PubMedCrossRefGoogle Scholar
  6. 6.
    Tiao GM, Alonso MH, Ryckman FC (2006) Pediatric liver transplantation. Semin Pediatr Surg 15:218–227PubMedCrossRefGoogle Scholar
  7. 7.
    Harada KM, Mandia-Sampaio EL, de Sandes-Freitas TV et al (2009) Risk factors associated with graft loss and patient survival after kidney transplantation. Transplant Proc 41:3667–3670PubMedCrossRefGoogle Scholar
  8. 8.
    Reding R (2005) Long-term complications of immunosuppression in pediatric liver recipients. Acta Gastroenterol Belg 68:453–456PubMedGoogle Scholar
  9. 9.
    Magee JC, Krishnan SM, Benfield MR (2008) Pediatric transplantation in the United States, 1997–2006. Am J Transplant 8:935–945PubMedCrossRefGoogle Scholar
  10. 10.
    Golomb J, Klutke CG, Lewin KJ et al (1989) Bladder neoplasms associated with augmentation cystoplasty: report of 2 cases and literature review. J Urol 142:377–380PubMedGoogle Scholar
  11. 11.
    Castagna MT, Mintz GS, Ohlmann P et al (2005) Incidence, location, magnitude, and clinical correlates of saphenous vein graft calcification: an intravascular ultrasound and angiographic study. Circulation 111:1148–1152PubMedCrossRefGoogle Scholar
  12. 12.
    Arul GS, Parikh D (2008) Oesophageal replacement in children. Ann R Coll Surg Engl 90:7–12PubMedCrossRefGoogle Scholar
  13. 13.
    Jaffe R, Strauss BH (2007) Late and very late thrombosis of drug-eluting stents: evolving concepts and perspectives. J Am Coll Cardiol 50:119–127PubMedCrossRefGoogle Scholar
  14. 14.
    Guyen O, Lewallen DG, Cabanela ME (2008) Modes of failure of osteonics constrained tripolar implants: a retrospective analysis of forty-three failed implants. J Bone Joint Surg Am 90:1553–1560PubMedCrossRefGoogle Scholar
  15. 15.
    Yukata K, Doi K, Hattori Y et al (2009) Early breakage of a titanium volar locking plate for fixation of a distal radius fracture: case report. J Hand Surg Am 34:907–909PubMedCrossRefGoogle Scholar
  16. 16.
    Schildhauer TA, Robie B, Muhr G et al (2006) Bacterial adherence to tantalum versus commonly used orthopedic metallic implant materials. J Orthop Trauma 20:476–484PubMedCrossRefGoogle Scholar
  17. 17.
    Jeandidier N, Riveline JP, Tubiana-Rufi N et al (2008) Treatment of diabetes mellitus using an external insulin pump in clinical practice. Diabetes Metab 34:425–438PubMedCrossRefGoogle Scholar
  18. 18.
    Piaggesi A (2004) Research development in the pathogenesis of neuropathic diabetic foot ulceration. Curr Diab Rep 4:419–423PubMedCrossRefGoogle Scholar
  19. 19.
    Senker J, Enzing C, Joly PB et al (2000) European exploitation of biotechnology-do government policies help? A recent survey of public spending on biotechnology in Europe suggests that money alone cannot stimulate growth of the sector. Nat Biotechnol 18:605–608PubMedCrossRefGoogle Scholar
  20. 20.
    Tabata Y (2009) Biomaterial technology for tissue engineering applications. J R Soc Interface 6(Suppl 3):S311–S324PubMedCrossRefGoogle Scholar
  21. 21.
    Williams DF (2009) On the nature of biomaterials. Biomaterials 30:5897–5909PubMedCrossRefGoogle Scholar
  22. 22.
    Burdick JA, Vunjak-Novakovic G. Engineered microenvironments for controlled stem cell differentiation. Tissue Eng Part A 15:205–219Google Scholar
  23. 23.
    Carrel A, Lindbergh C (1938) The culture of organs. Paul B. Hoeber Inc., Harper Brothers, New YorkGoogle Scholar
  24. 24.
    Bianco P, Robey PG (2001) Stem cells in tissue engineering. Nature 414:118–121PubMedCrossRefGoogle Scholar
  25. 25.
    Vats A, Bielby RC, Tolley NS et al (2005) Stem cells. Lancet 366:592–602PubMedCrossRefGoogle Scholar
  26. 26.
    Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147PubMedCrossRefGoogle Scholar
  27. 27.
    Solter D, Gearhart J (1999) Putting stem cells to work. Science 283:1468–1470PubMedCrossRefGoogle Scholar
  28. 28.
    Vogel G (1999) Harnessing the power of stem cells. Science 283:1432–1434PubMedCrossRefGoogle Scholar
  29. 29.
    Amit M, Carpenter MK, Inokuma MS et al (2000) Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev Biol 227:271–278PubMedCrossRefGoogle Scholar
  30. 30.
    Odorico JS, Kaufman DS, Thomson JA (2001) Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19:193–204PubMedCrossRefGoogle Scholar
  31. 31.
    Cowan CA, Klimanskaya I, McMahon J et al (2004) Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med 350:1353–1356PubMedCrossRefGoogle Scholar
  32. 32.
    Schuldiner M, Itskovitz-Eldor J, Benvenisty N (2003) Selective ablation of human embryonic stem cells expressing a “suicide” gene. Stem Cells 21:257–265PubMedCrossRefGoogle Scholar
  33. 33.
    Drukker M, Katz G, Urbach A et al (2002) Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci USA 99:9864–9869PubMedCrossRefGoogle Scholar
  34. 34.
    Lysaght MJ (2003) Immunosuppression, immunoisolation and cell therapy. Mol Ther 7:432PubMedCrossRefGoogle Scholar
  35. 35.
    Hall VJ, Stojkovic P, Stojkovic M (2006) Using therapeutic cloning to fight human disease: a conundrum or reality? Stem Cells 24:1628–1637PubMedCrossRefGoogle Scholar
  36. 36.
    Colman A, Kind A (2000) Therapeutic cloning: concepts and practicalities. Trends Biotechnol 18:192–196PubMedCrossRefGoogle Scholar
  37. 37.
    Priddle H, Jones DR, Burridge PW et al (2006) Hematopoiesis from human embryonic stem cells: overcoming the immune barrier in stem cell therapies. Stem Cells 24:815–824PubMedCrossRefGoogle Scholar
  38. 38.
    Raikwar SP, Mueller T, Zavazava N (2006) Strategies for developing therapeutic application of human embryonic stem cells. Physiology (Bethesda) 21:19–28Google Scholar
  39. 39.
    Tian X, Kaufman DS (2005) Hematopoietic development of human embryonic stem cells in culture. Methods Mol Med 105:425–436PubMedGoogle Scholar
  40. 40.
    Trounson A (2006) The production and directed differentiation of human embryonic stem cells. Endocr Rev 27:208–219PubMedCrossRefGoogle Scholar
  41. 41.
    Leker RR, McKay RD (2004) Using endogenous neural stem cells to enhance recovery from ischemic brain injury. Curr Neurovasc Res 1:421–427PubMedCrossRefGoogle Scholar
  42. 42.
    Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776PubMedCrossRefGoogle Scholar
  43. 43.
    Kuroda R, Usas A, Kubo S et al (2006) Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis Rheum 54:433–442PubMedCrossRefGoogle Scholar
  44. 44.
    Walkup MH, Gerber DA (2006) Hepatic stem cells: in search of. Stem Cells 24:1833–1840PubMedCrossRefGoogle Scholar
  45. 45.
    Zalzman M, Anker-Kitai L, Efrat S (2005) Differentiation of human liver-derived, insulin-producing cells toward the beta-cell phenotype. Diabetes 54:2568–2575PubMedCrossRefGoogle Scholar
  46. 46.
    Raghunath J, Salacinski HJ, Sales KM et al (2005) Advancing cartilage tissue engineering: the application of stem cell technology. Curr Opin Biotechnol 16:503–509PubMedCrossRefGoogle Scholar
  47. 47.
    Riha GM, Lin PH, Lumsden AB, Yao Q (2005) Review: application of stem cells for vascular tissue engineering. Tissue Eng 11:1535–1552PubMedCrossRefGoogle Scholar
  48. 48.
    Risbud MV, Shapiro IM (2005) Stem cells in craniofacial and dental tissue engineering. Orthod Craniofac Res 8:54–59PubMedGoogle Scholar
  49. 49.
    Bruder SP, Fink DJ, Caplan AI (1994) Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem 56:283–294PubMedCrossRefGoogle Scholar
  50. 50.
    Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5:362–369PubMedCrossRefGoogle Scholar
  51. 51.
    De Coppi P, Bartsch G, Siddiqui MM et al (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106PubMedCrossRefGoogle Scholar
  52. 52.
    Miki T, Lehmann T, Cai H et al (2005) Stem cell characteristics of amniotic epithelial cells. Stem Cells 23:1549–1559PubMedCrossRefGoogle Scholar
  53. 53.
    Saxena AK (2005) Tissue engineering: present concepts and strategies. J Indian Assoc Pediatr Surg 10:14–19CrossRefGoogle Scholar
  54. 54.
    Langer R, Tirrell DA (2004) Designing materials for biology and medicine. Nature 428:487–492PubMedCrossRefGoogle Scholar
  55. 55.
    Boccaccini AR, Blaker JJ (2005) Bioactive composite materials for tissue engineering scaffolds. Expert Rev Med Devices 2:303–317PubMedCrossRefGoogle Scholar
  56. 56.
    Behonick DJ, Werb Z (2003) A bit of give and take: the relationship between the extracellular matrix and the developing chondrocyte. Mech Dev 120:1327–1336PubMedCrossRefGoogle Scholar
  57. 57.
    Ma Z, He W, Yong T et al (2005) Grafting of gelatin on electrospun poly(caprolactone) nanofibers to improve endothelial cell spreading and proliferation and to control cell orientation. Tissue Eng 11:1149–1158PubMedCrossRefGoogle Scholar
  58. 58.
    Rho KS, Jeong L, Lee G et al (2006) Electrospinning of collagen nanofibers: effects on the behavior of normal human keratinocytes and early-stage wound healing. Biomaterials 27:1452–1461PubMedCrossRefGoogle Scholar
  59. 59.
    Ayutsede J, Gandhi M, Sukigara S et al (2006) Carbon nanotube-reinforced Bombyx morisilk nanofibers by the electrospinning process. Biomacromolecules 7:208–224PubMedCrossRefGoogle Scholar
  60. 60.
    Stankus JJ, Guan J, Fujimoto K et al (2006) Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix. Biomaterials 27:735–744PubMedCrossRefGoogle Scholar
  61. 61.
    Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1880PubMedCrossRefGoogle Scholar
  62. 62.
    Nguyen KT, West JL (2002) Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23:4307–4314PubMedCrossRefGoogle Scholar
  63. 63.
    Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23:47–55PubMedCrossRefGoogle Scholar
  64. 64.
    Tibbitt MW, Anseth KS (2009) Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103:655–663PubMedCrossRefGoogle Scholar
  65. 65.
    Grayson WL, Zhao F, Izadpanah R et al (2006) Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs. J Cell Physiol 207:331–339PubMedCrossRefGoogle Scholar
  66. 66.
    Niklason LE, Gao J, Abbott WM et al (1999) Functional arteries grown in vitro. Science 284:489–493PubMedCrossRefGoogle Scholar
  67. 67.
    Barron V, Lyons E, Stenson-Cox C et al (2003) Bioreactors for cardiovascular cell and tissue growth: a review. Ann Biomed Eng 31:1017–1030PubMedCrossRefGoogle Scholar
  68. 68.
    Eschenhagen T, Fink C, Remmers U et al (1997) Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart model system. FASEB J 11:683–694PubMedGoogle Scholar
  69. 69.
    Carrier RL, Papadaki M, Rupnick M et al (1999) Cardiac tissue engineering: cell seeding, cultivation parameters and tissue construct characterization. Biotechnol Bioeng 64:580–589PubMedCrossRefGoogle Scholar
  70. 70.
    Zimmermann WH, Melnychenko I, Wasmeier G et al (2006) Engineered heart tissue grafts improve systolic and diastolic function in infracted rat hearts. Nat Med 12:452–458PubMedCrossRefGoogle Scholar
  71. 71.
    Guo XM, Zhao YS, Chang HX et al (2006) Creation of engineered cardiac tissue in vitro from mouse embryonic stem cells. Circulation 113:2229–2237PubMedCrossRefGoogle Scholar
  72. 72.
    Shimizu T, Yamato M, Isoi Y et al (2002) Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Cir Res 90:e40–e48CrossRefGoogle Scholar
  73. 73.
    Guo Y, Zhang XZ, Wei Y et al (2009) Culturing of ventricle cells at high density and construction of engineered cardiac cell sheets without scaffold. Int Heart J 50:653–662PubMedCrossRefGoogle Scholar
  74. 74.
    Shinoka T, Ma PX, Shum-Tim D et al (1996) Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation 94(Suppl 9):II164–II168Google Scholar
  75. 75.
    Schnell AM, Hoerstrup SP, Zund G et al (2001) Optimal cell source for cardiovascular tissue engineering: venous vs. aortic human myofibroblasts. Thorac Cardiovasc Surg 49:221–225PubMedCrossRefGoogle Scholar
  76. 76.
    Sutherland FWH, Perry TE, Nasseri BA et al (2002) Advances in the mechanisms of cell delivery to cardiovascular scaffolds: comparison of two rotating cell culture systems. ASAIO J 48:346–349PubMedCrossRefGoogle Scholar
  77. 77.
    Engelmayr GC, Hildebrand DK, Sutherland FW et al (2003) A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart-valve biomaterials. Biomaterials 24:2523–2532PubMedCrossRefGoogle Scholar
  78. 78.
    Dohmen PM, Lembcke A, Hotz H et al (2002) Ross operation with a tissue-engineered heart valve. Ann Thorac Surg 74:1438–1442PubMedCrossRefGoogle Scholar
  79. 79.
    Dohmen PM, Lembcke A, Holinski S et al (2007) Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the Ross procedure. Ann Thorac Surg 84:729–736PubMedCrossRefGoogle Scholar
  80. 80.
    Shinoka T, Breuer C (2008) Tissue-engineered blood vessels in pediatric cardiac surgery. Yale J Biol Med 81:161–166PubMedGoogle Scholar
  81. 81.
    Narushima M, Kobayashi N, Okitsu T et al (2005) A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol 23:1274–1282PubMedCrossRefGoogle Scholar
  82. 82.
    Yanagita M, Nakayama K, Takeuchi T (1992) Processing of mutated proinsulin with tetrabasic cleavage sites to bioactive insulin in the nonendocrine cell line, COS-7. FEBS Lett 311:55–59PubMedCrossRefGoogle Scholar
  83. 83.
    Bonner-Weir S, Sharma A (2002) Pancreatic stem cells. J Pathol 197:519–526PubMedCrossRefGoogle Scholar
  84. 84.
    Jun HS, Yoon JW (2005) Approaches for the cure of type 1 diabetes by cellular and gene therapy. Curr Gene Ther 5:249–262PubMedCrossRefGoogle Scholar
  85. 85.
    Mikos A, Papadaki M, Kouvroukoglou S et al (1994) Mini-review: islet transplantation to create a bioartificial pancreas. Biotechnol Bioeng 43:673–677PubMedCrossRefGoogle Scholar
  86. 86.
    Soon-Shiong P, Heintz RE, Merideth N et al (1994) Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 343:950–951PubMedCrossRefGoogle Scholar
  87. 87.
    Calafiore R, Basta G, Luca G et al (2006) Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care 29:137–138PubMedCrossRefGoogle Scholar
  88. 88.
    Tuch BE, Keogh GW, Williams LJ et al (2009) Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 32:1887–1889PubMedCrossRefGoogle Scholar
  89. 89.
    Takimoto Y, Okumura N, Nakamura T et al (1993) Long-term follow-up of the experimental replacement of the esophagus with a collagen–silicone composite tube. ASAIO J 39:M736–M739PubMedCrossRefGoogle Scholar
  90. 90.
    Yamamoto Y, Nakamura T, Shimizu Y et al (1999) Intrathoracic esophageal replacement in the dog with the use of an artificial esophagus composed of a collagen sponge with a double-layered silicone tube. J Thorac Cardiovasc Surg 118:276–286PubMedCrossRefGoogle Scholar
  91. 91.
    Yamamoto Y, Nakamura T, Shimizu Y et al (2000) Intrathoracic esophageal replacement with a collagen sponge–silicone double-layer tube: evaluation of omental-pedicle wrapping and prolonged placement of an inner stent. ASAIO J 46:734–739PubMedCrossRefGoogle Scholar
  92. 92.
    Hori Y, Nakamura T, Kimura D et al (2003) Effect of basic fibroblast growth factor on vascularization in esophagus tissue engineering. Int J Artif Organs 26:241–244PubMedGoogle Scholar
  93. 93.
    Sato M, Ando N, Ozawa S et al (1994) An artificial esophagus consisting of cultured human esophageal epithelial cells, polyglycolic acid mesh, and collagen. ASAIO J 40:M389–M392PubMedCrossRefGoogle Scholar
  94. 94.
    Hayashi K, Ando N, Ozawa S et al (2004) A neo-esophagus reconstructed by cultured human esophageal epithelial cells, smooth muscle cells, fibroblasts, and collagen. ASAIO J 50:261–266PubMedCrossRefGoogle Scholar
  95. 95.
    Badylak S, Meurling S, Chen M et al (2000) Resorbable bioscaffold for esophageal repair in a dog model. J Pediatr Surg 35:1097–1103PubMedCrossRefGoogle Scholar
  96. 96.
    Badylak SF, Vorp DA, Spievack AR et al (2005) Esophageal reconstruction with ECM and muscle tissue in a dog model. J Surg Res 128:87–97PubMedGoogle Scholar
  97. 97.
    Doede T, Bondartschuk M, Joerck C et al (2009) Unsuccessful alloplastic esophageal replacement with porcine small intestinal submucosa. Artif Organs 33:328–333PubMedCrossRefGoogle Scholar
  98. 98.
    Nakase Y, Nakamura T, Kin S et al (2008) Intrathoracic esophageal replacement by in situ tissue-engineered esophagus. J Thorac Cardiovasc Surg 136:850–859PubMedCrossRefGoogle Scholar
  99. 99.
    Grikscheit T, Ochoa ER, Srinivasan A et al (2003) Tissue-engineered esophagus: experimental substitution by onlay patch or interposition. J Thorac Cardiovasc Surg 126:537–544PubMedCrossRefGoogle Scholar
  100. 100.
    Saxena AK, Ainoedhofer H, Höllwarth ME (2009) Esophagus tissue engineering: in vitro generation of esophageal epithelial cell sheets and viability on scaffold. J Pediatr Surg 44:896–901PubMedCrossRefGoogle Scholar
  101. 101.
    Saxena AK, Kofler K, Ainödhofer H et al (2009) Esophagus tissue engineering: hybrid approach with esophageal epithelium and unidirectional smooth muscle tissue component generation in vitro. J Gastrointest Surg 13:1037–1043PubMedCrossRefGoogle Scholar
  102. 102.
    Soltysiak P, Saxena AK (2009) Micro-computed tomography for implantation site imaging during in situ oesophagus tissue engineering in a live small animal model. J Tissue Eng Regen Med 3:573–576PubMedCrossRefGoogle Scholar
  103. 103.
    Saxena AK, Ainoedhofer H, Höllwarth ME (2010) Culture of ovine esophageal epithelial cells and in vitro esophagus tissue engineering. Tissue Eng Part C Methods 16:109–114Google Scholar
  104. 104.
    Kofler K, Ainoedhofer H, Höllwarth ME et al (2010) Fluorescence-activated cell sorting of PCK-26 antigen-positive cells enables selection of ovine esophageal epithelial cells with improved viability on scaffolds for esophagus tissue engineering. Pediatr Surg Int 26:97–104PubMedCrossRefGoogle Scholar
  105. 105.
    Saxena AK, Soltysiak P, Ainoedhofer H (2009) Esophagus tissue engineering: In situ generation of vascularized esophageal conduits using the ovine model. Abstracts of the 41st Annual Meeting of the Canadian Association of Pediatric Surgeons, Oct 1–4, Halifax, Nova Scotia, CanadaGoogle Scholar
  106. 106.
    Vacanti JP, Morse MA, Saltzman WM et al (1998) Selective cell transplantation using bioabsorbable artificial polymers as matrices. J Pediatr Surg 23:3–9CrossRefGoogle Scholar
  107. 107.
    Patel HR, Tait IS, Evans GS et al (1996) Influence of cell interactions in a novel model of postnatal mucosal regeneration. Gut 38:679–686PubMedCrossRefGoogle Scholar
  108. 108.
    Evans GS, Flint N, Somers AS et al (1992) The development of a method for the preparation of rat intestinal epithelial cell primary cultures. J Cell Sci 101:219–231PubMedGoogle Scholar
  109. 109.
    Tait IS, Flint N, Campbell FC et al (1994) Generation of neomucosa in vivo by transplantation of dissociated rat postnatal small-intestinal epithelium. Differentiation 56:91–100PubMedGoogle Scholar
  110. 110.
    Tait IS, Evans GS, Flint N et al (1994) Colonic mucosal replacement by syngeneic small intestinal stem cell transplantation. Am J Surg 167:67–72PubMedCrossRefGoogle Scholar
  111. 111.
    Choi RS, Riegler M, Pothoulakis C et al (1998) Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine. J Pediatr Surg 33:991–996PubMedCrossRefGoogle Scholar
  112. 112.
    Kim SS, Kaihara S, Benvenuto MS et al (1999) Effects of anastomosis of tissue engineered neointestine to native small bowel. J Surg Res 87:6–13PubMedCrossRefGoogle Scholar
  113. 113.
    Grikscheit TC, Siddique A, Ochoa ER et al (2004) Tissue-engineered small intestine improves recovery after massive small bowel resection. Ann Surg 240:748–754PubMedCrossRefGoogle Scholar
  114. 114.
    Lloyd DA, Ansari TI, Gundabolu P et al (2006) A pilot study investigating a novel subcutaneously implanted precellularized scaffold for tissue engineering of intestinal mucosa. Eur Cell Mater 11:27–33PubMedGoogle Scholar
  115. 115.
    Sala FG, Kunisaki SM, Ochoa ER et al (2009) Tissue-engineered small intestine and stomach form from autologous tissue in a preclinical large animal model. J Surg Res 156:205–212PubMedCrossRefGoogle Scholar
  116. 116.
    Nony PA, Schnellmann RG (2003) Mechanisms of renal cell repair and regeneration after acute renal failure. J Pharmacol Exp Ther 304:905–912PubMedCrossRefGoogle Scholar
  117. 117.
    Al-Awqati Q, Oliver JA (2002) Stem cells in the kidney. Kidney Int 61:387–395PubMedCrossRefGoogle Scholar
  118. 118.
    Oliver JA, Maarouf O, Cheema FH et al (2004) The renal papilla is a niche for adult kidney stem cells. J Clin Invest 114:795–804PubMedGoogle Scholar
  119. 119.
    Duffield JS, Park KM, Hsiao LL 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 115:1743–1755PubMedCrossRefGoogle Scholar
  120. 120.
    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 115:1756–1764PubMedCrossRefGoogle Scholar
  121. 121.
    Brodie JC, Humes HD (2005) Stem cell approaches for the treatment of renal failure. Pharmacol Rev 57:299–313PubMedCrossRefGoogle Scholar
  122. 122.
    Steenhard BM, Isom KS, Cazcarro P et al (2005) Integration of embryonic stem cells in metanephric kidney organ culture. J Am Soc Nephrol 16:1623–1631PubMedCrossRefGoogle Scholar
  123. 123.
    Wang PC, Takezawa T (2005) Reconstruction of renal glomerular tissue using collagen vitrigel scaffold. J Biosci Bioeng 99:529–540PubMedCrossRefGoogle Scholar
  124. 124.
    Joraku A, Stern KA, Atala A et al (2009) In vitro generation of three-dimensional renal structures. Methods 47:129–133PubMedCrossRefGoogle Scholar
  125. 125.
    Roessger A, Denk L, Minuth WW (2009) Potential of stem/progenitor cell cultures within polyester fleeces to regenerate renal tubules. Biomaterials 30:3723–3732PubMedCrossRefGoogle Scholar
  126. 126.
    Kropp BP, Cheng EY, Lin HK et al (2004) Reliable and reproducible bladder regeneration using unseeded distal small intestinal ubmucosa. J Urol 172:1710–1713PubMedCrossRefGoogle Scholar
  127. 127.
    Yoo JJ, Meng J, Oberpenning F et al (1998) Bladder augmentation using allogenic bladder submucosa seeded with cells. Urology 51:221–225PubMedCrossRefGoogle Scholar
  128. 128.
    Probst M, Dahiya R, Carrier S et al (1997) Reproduction of functional smooth muscle tissue and partial bladder replacement. Br J Urol 79:505–515PubMedGoogle Scholar
  129. 129.
    Portis AJ, Elbahnasy AM, Shalhav AL et al (2000) Laparoscopic augmentation cystoplasty with different biodegradable grafts in an animal model. J Urol 164:1405–1411PubMedCrossRefGoogle Scholar
  130. 130.
    Landman J, Olweny E, Sundaram CP et al (2004) Laparoscopic mid-sagittal hemicystectomy and bladder reconstruction with small intestinal submucosa and reimplantation of ureter into small intestinal submucosa: 1-year follow-up. J Urol 171:2450–2455PubMedCrossRefGoogle Scholar
  131. 131.
    Oberpenning FO, Meng J, Yoo J et al (1999) De novo reconstitution of a functional urinary bladder by tissue engineering. Nat Biotechnol 17:149–155PubMedCrossRefGoogle Scholar
  132. 132.
    Atala A, Bauer SB, Soker S et al (2006) Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246PubMedCrossRefGoogle Scholar
  133. 133.
    Soler R, Fullhase C, Atala A et al (2009) Regenerative medicine strategies for treatment of neurogenic bladder. Therapy 6:177–184PubMedCrossRefGoogle Scholar
  134. 134.
    Guillouzo A (1998) Liver cell models in in vitro toxicology. Environ Health Perspect 106:511–532PubMedCrossRefGoogle Scholar
  135. 135.
    Mitaka T (1998) The current status of primary hepatocyte culture. Int J Exp Pathol 79:393–409PubMedCrossRefGoogle Scholar
  136. 136.
    Ranucci CS, Kumar A, Batra SP et al (2000) Control of hepatocyte function on collagen foams: sizing matrix pores toward selective induction of 2D and 3D cellular morphogenesis. Biomaterials 21:783–793PubMedCrossRefGoogle Scholar
  137. 137.
    Seo SJ, Choi YJ, Akaike T et al (2006) Alginate/galactosylated chitosan/heparin scaffold as a new synthetic extracellular matrix for hepatocytes. Tissue Eng 12:33–44PubMedCrossRefGoogle Scholar
  138. 138.
    Tan W, Desai TA (2003) Microfluidic patterning of cells in extracellular matrix biopolymers: effects of channel size, cell type, and matrix composition on pattern integrity. Tissue Eng 9:255–267PubMedCrossRefGoogle Scholar
  139. 139.
    Wang X, Yan Y, Pan Y et al (2006) Generation of three-dimensional hepatocyte/gelatin structures with rapid prototyping system. Tissue Eng 12:83–90PubMedCrossRefGoogle Scholar
  140. 140.
    Kaihara S, Borenstein J, Koka R et al (2000) Silicon micromachining to tissue engineer branched vascular channels for liver fabrication. Tissue Eng 6:105–117PubMedCrossRefGoogle Scholar
  141. 141.
    Allen JW, Khetani SR, Bhatia SN (2005) In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol Sci 84:110–119PubMedCrossRefGoogle Scholar
  142. 142.
    Gebhardt R, Hengstler JG, Muller D et al (2003) New hepatocyte in vitro systems for drug metabolism: metabolic capacity and recommendations for application in basic research and drug development, standard operation procedures. Drug Metab Rev 35:145–213PubMedCrossRefGoogle Scholar
  143. 143.
    Hong KU, Reynolds SD, Giangreco A et al (2001) Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol 24:671–681PubMedGoogle Scholar
  144. 144.
    Kim CF, Jackson EL, Woolfenden AE (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823–835PubMedCrossRefGoogle Scholar
  145. 145.
    Coraux C, Nawrocki-Raby B, Hinnrasky J et al (2005) Embryonic stem cells generate airway epithelial tissue. Am J Respir Cell Mol Biol 32:87–92PubMedCrossRefGoogle Scholar
  146. 146.
    Van Vranken BE, Romanska HM, Polak JM (2005) Coculture of embryonic stem cells with pulmonary mesenchyme: a microenvironment that promotes differentiation of pulmonary epithelium. Tissue Eng 11:1177–1187PubMedCrossRefGoogle Scholar
  147. 147.
    Saxena AK, Marler J, Benvenuto M (1999) Skeletal muscle tissue engineering using isolated myoblasts on synthetic biodegradable polymers: preliminary studies. Tissue Eng 5:525–532PubMedCrossRefGoogle Scholar
  148. 148.
    Saxena AK, Willital GH, Vacanti JP (2001) Vascularized three-dimensional skeletal muscle tissue-engineering. Biomed Mater Eng 11:275–281PubMedGoogle Scholar
  149. 149.
    Tsang VL, Bhatia SN (2004) Three-dimensional tissue fabrication. Adv Drug Deliv Rev 56:1635–1647PubMedCrossRefGoogle Scholar
  150. 150.
    Costa KD, Lee EJ, Holmes JW (2003) Creating alignment and anisotropy in engineered heart tissue: Role of boundary conditions in a model three-dimensional culture system. Tissue Eng 9:567–577PubMedCrossRefGoogle Scholar
  151. 151.
    Girton TS, Barocas VH, Tranquillo RT (2002) Confined compression of a tissue-equivalent: collagen fibril and cell alignment in response to anisotropic strain. J Biomech Eng 124:568–575PubMedCrossRefGoogle Scholar
  152. 152.
    Taylor NA, Wilkinson JG (1986) Exercise-induced skeletal muscle growth. Hypertrophy or hyperplasia? Sports Med 3:190–200PubMedCrossRefGoogle Scholar
  153. 153.
    Vandenburgh HH, Karlisch P (1989) Longitudinal growth of skeletal myotubes in vitro in a new horizontal mechanical cell stimulator. In Vitro Cell Dev Biol 25:607–616PubMedCrossRefGoogle Scholar
  154. 154.
    Cheema U, Yang SY, Mudera V (2003) 3-D in vitro model of early skeletal muscle development. Cell Motil Cytoskeleton 54:226–236PubMedCrossRefGoogle Scholar
  155. 155.
    Tatsumi R, Sheehan SM, Iwasaki H (2001) Mechanical stretch induces activation of skeletal muscle satellite cells in vitro. Exp Cell Res 267:107–114PubMedCrossRefGoogle Scholar
  156. 156.
    Darr KC, Schultz E (1987) Exercise-induced satellite cell activation in growing and mature skeletal muscle. J Appl Physiol 63:1816–1821PubMedGoogle Scholar
  157. 157.
    Kook SH, Lee HJ, Chung WT et al (2008) Cyclic mechanical stretch stimulates the proliferation of C2C12 myoblasts and inhibits their differentiation via prolonged activation of p38 MAPK. Mol Cells 25(4):479–486PubMedGoogle Scholar
  158. 158.
    Otis JS, Burkholder TJ, Pavlath GK (2005) Stretch-induced myoblast proliferation is dependent on the COX2 pathway. Exp Cell Res 310:417–425PubMedCrossRefGoogle Scholar
  159. 159.
    Fujita H, Nedachi T, Kanzaki M (2007) Accelerated de novo sarcomere assembly by electric pulse stimulation in C2C12 myotubes. Exp Cell Res 313:1853–1865PubMedCrossRefGoogle Scholar
  160. 160.
    De Deyne PG (2000) Formation of sarcomeres in developing myotubes: Role of mechanical stretch and contractile activation. Am J Physiol Cell Physiol 279:C1801–C1811PubMedGoogle Scholar
  161. 161.
    Larkin LM, Van der Meulen JH, Dennis RG (2006) Functional evaluation of nerve-skeletal muscle constructs engineered in vitro. In Vitro Cell Dev Biol Anim 42:75–82PubMedCrossRefGoogle Scholar
  162. 162.
    Dhawan V, Lytle IF, Dow DE (2007) Neurotization improves contractile forces of tissue-engineered skeletal muscle. Tissue Eng 13:2813–2821PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Experimental Fetal Surgery and Tissue Engineering Unit, Department of Pediatric and Adolescent SurgeryMedical University of GrazGrazAustria

Personalised recommendations