Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Gene Therapy Progress and Prospects: In tissue engineering

Abstract

Tissue engineering (TE) has existed for several years as an area spanning many disciplines, including medicine and engineering. The use of stem cells as a biological basis for TE coupled with advances in materials science has opened up an entirely new chapter in medicine and holds the promise of major contributions to the repair, replacement and regeneration of damaged tissues and organs. In this article, we review the spectrum of stem cells and scaffolds being investigated for their potential applications in medicine.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Hench LL, Xynos ID, Polak JM . Bioactive glasses for in situ tissue regeneration. J Biomater Sci Polym Ed 2004; 15: 543–562.

    CAS  PubMed  Google Scholar 

  2. Christodoulou I et al. Dose- and time-dependent effect of bioactive gel-glass ionic dissolution products on human fetal osteoblast-gene expression. J Biomed Mater Res B 2005; 74: 529–537.

    Google Scholar 

  3. Montjovent MO et al. Fetal bone cells for tissue engineering. Bone 2004; 35: 1323–1333.

    CAS  PubMed  Google Scholar 

  4. Bhattacharya N . Fetal cell/tissue therapy in adult disease: a new horizon in regenerative medicine. Clin Exp Obstet Gynecol 2004; 31: 167–173.

    CAS  PubMed  Google Scholar 

  5. Draper JS et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 2004; 22: 53–54.

    CAS  PubMed  Google Scholar 

  6. Chambers I et al. Functional expression cloning of nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003; 113: 643–655.

    CAS  PubMed  Google Scholar 

  7. Reim G et al. The POU domain protein spg (pou2/Oct4) is essential for endoderm formation in cooperation with the HMG domain protein casanova. Dev Cell 2004; 6: 91–101.

    CAS  PubMed  Google Scholar 

  8. Nusse R . Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface. Development 2003; 130: 5297–5305.

    CAS  PubMed  Google Scholar 

  9. Sato N et al. Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 2003; 260: 404–413.

    CAS  PubMed  Google Scholar 

  10. Sperger JM et al. Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci USA 2003; 100: 13350–13355.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Richards M et al. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 2004; 22: 51–64.

    CAS  PubMed  Google Scholar 

  12. Brandenberger R et al. MPSS profiling of human embryonic stem cells. BMC Dev Biol 2004; 4: 10.

    PubMed  PubMed Central  Google Scholar 

  13. Neimeyer P et al. Allogenic transplantation of human mesenchymal stem cells for tissue engineering purposes: an in vitro study. Orthopedics 2004; 33: 1346–1353.

    Google Scholar 

  14. Hwang WS et al. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 2004; 303: 1669–1674.

    CAS  PubMed  Google Scholar 

  15. Hwang WS et al. Patient-specific embryonic stem cells derived from human SCNT blastocytes. Science 2005; 308: 1777–1783.

    CAS  PubMed  Google Scholar 

  16. Bielby RC et al. Time- and concentration-dependent effects of dissolution products of 58S sol–gel bioactive glass on proliferation and differentiation of murine and human osteoblasts. Tissue Eng 2004; 10: 1018–1026.

    CAS  PubMed  Google Scholar 

  17. Rippon HJ, Ali NN, Polak JM, Bishop AE . Initial observations on the effect of medium composition on the differentiation of murine embryonic stem cells to alveolar type II cells. Cloning Stem Cells 2004; 6: 49–56.

    CAS  PubMed  Google Scholar 

  18. Samadikuchaksaraei A, Polak JM, Bishop AE . Derivation of type II pneumocytes from human embryonic stem cells. Am J Respir Crit Care Med 2004; 169: A87.

    Google Scholar 

  19. Tai G et al. Differentiation of osteoblasts from murine embryonic stem cells by overexpression of the transcriptional factor osterix. Tissue Eng 2004; 10: 1456–1466.

    CAS  PubMed  Google Scholar 

  20. Bieberich E et al. Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants. J Cell Biol 2004; 167: 723–734.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Matin MM et al. Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells 2004; 22: 659–668.

    CAS  PubMed  Google Scholar 

  22. Ball SG, Shuttleworth AC, Kielty CM . Direct cell contact influences bone marrow mesenchymal stem cell fate. Int J Biochem Cell Biol 2004; 36: 714.

    CAS  PubMed  Google Scholar 

  23. Hwang JH et al. Differentiation of stem cells isolated from rat smooth muscle. Mol Cells 2004; 17: 57.

    CAS  PubMed  Google Scholar 

  24. Van Vranken BE et al. Co-culture of embryonic stem cells with pulmonary mesenchyme: a microenvironment that promotes differentiation of pulmonary epithelium. Tissue Eng 2005 (in press).

  25. Raff M . Adult stem cell plasticity: fact or artefact. Annu Rev Cell Dev Biol 2003; 19: 1–22.

    CAS  PubMed  Google Scholar 

  26. Verfaillie CM et al. Stem cells: hype and reality. Hematology (Am Soc Hematol Educ Program) 2002; 369–391.

    Google Scholar 

  27. Lakshmipathy U, Verfaillie C . Stem cell plasticity. Blood Rev 2005; 19: 29–38.

    PubMed  Google Scholar 

  28. Anjos-Afonso F, Bonnet D . Definition of a new hierarchy in the murine mesenchymal stem cell (muMSC) compartment with the identification and isolation of a quiescent sub-population expressing SSEA-1 antigen. Blood 2003; 112: 415.

    Google Scholar 

  29. Dominici M et al. Hematopoietic cells and osteoblasts are derived from a common marrow progenitor afterbone marrow transplantation. Proc Natl Acad Sci USA 2004; 101: 11761–11766.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Suratt BT et al. Human pulmonary chimerism after hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2003; 168: 318–322.

    PubMed  Google Scholar 

  31. Mattsson J, Jansson M, Wernerson A, Hassan M . Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation. Transplantation 2004; 78: 154–157.

    PubMed  Google Scholar 

  32. Kleeberger W et al. Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury. Am J Pathol 2003; 162: 1487–1494.

    PubMed  PubMed Central  Google Scholar 

  33. Albera CS et al. Repopulation of human pulmonary epithelium by bone marrow cells: a potential means to promote repair. Tissue Eng 2005 (in press).

  34. Stenderup K et al. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003; 33: 919–926.

    PubMed  Google Scholar 

  35. Wickham MQ et al. Multipotent human adult stem cells derived from infrapatellar fat pad of the knee. Clin Orthop 2003; 412: 196.

    Google Scholar 

  36. Yen BL et al. Isolation of multipotent cells from human term placenta. Stem Cells 2005; 23: 3–9.

    CAS  PubMed  Google Scholar 

  37. Kodama S, Davis M, Faustman DL . Diabetes and stem cell researchers turn to the lowly spleen. Sci Aging Knowledge Environ 2005; 3: pe2.

    Google Scholar 

  38. Kehat I et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 2004; 22: 1282–1289.

    CAS  PubMed  Google Scholar 

  39. Menasche P et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003; 41: 1078–1083.

    PubMed  Google Scholar 

  40. Rubart M et al. Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ Res 2003; 92: 1217–1224.

    CAS  PubMed  Google Scholar 

  41. Ikeda R et al. Transplantation of motorneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice. Exp Neurol 2004; 189: 280–294.

    CAS  PubMed  Google Scholar 

  42. Otani A et al. Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative haematopoietic stem cells. J Clin Invest 2004; 114: 765–774.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hicok KC et al. Human adipose-derived adult stem cells produce osteoid in vivo. Tissue Eng 2004; 10: 371–380.

    CAS  PubMed  Google Scholar 

  44. Fraidenraich DE et al. Rescue of cardiac defects in Id knockout embryos by injection of embryonic stem cells. Science 2004; 306: 247–252.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Chien KR, Moretti A, Laugwitz KL . Development. ES Cells to the rescue. Science 2004; 306: 239–240.

    CAS  PubMed  Google Scholar 

  46. Imitola J et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 2004; 101: 18117–18122.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Henning RJ et al. Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction. Cell Transplant 2005; 13: 729–739.

    Google Scholar 

  48. Schachinger V et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004; 44: 1690–1699.

    PubMed  Google Scholar 

  49. Wollert KC et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004; 364: 141–148.

    PubMed  Google Scholar 

  50. Fernandez-Aviles F et al. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 2004; 95: 742–748.

    CAS  PubMed  Google Scholar 

  51. Jones JR, Hench LL . Regeneration of trabecular bone using porous ceramics. Curr Opin Solid State Mater Sci 2003; 7: 301–307.

    CAS  Google Scholar 

  52. Bielby RC, Pryce RS, Hench LL, Polak JM . Enhanced derivation of osteogenic cells from murine embryonic stem cells after treatment with ionic dissolution products of 58S bioactive sol–gel glass. Tissue Eng 2005; 11: 479–488.

    CAS  PubMed  Google Scholar 

  53. Langer R, Tirrell DA . Designing materials for biology and medicine. Nature 2004; 428: 487–492.

    CAS  PubMed  Google Scholar 

  54. Lutolf MP, Hubbell JA . Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechn 2005; 23: 47–55.

    CAS  Google Scholar 

  55. Kleinman HK, Phiilip D, Hoffman MP . Role of the extracellular matrix in morphogenesis. Curr Opin Biotechnol 2003; 14: 526–532.

    CAS  PubMed  Google Scholar 

  56. Zhang S . Fabrication of novel biomaterials through molecular self-assembly. Nat Biotechnol 2003; 21: 1171–1178.

    CAS  PubMed  Google Scholar 

  57. Hersel U, Dahmen C, Kessler H . RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 2003; 24: 4385–4415.

    CAS  PubMed  Google Scholar 

  58. Shin H, Jo S, Mikos AG . Biomimetic materials for tissue engineering. Biomaterials 2003; 24: 4353–4364.

    CAS  PubMed  Google Scholar 

  59. Silva GA et al. Selective differentiation of neural progenitor cells by high epitope-density nanofibers. Science 2004; 303: 1352–1355.

    CAS  PubMed  Google Scholar 

  60. Gunn JW, Turner SD, Mann BK . Adhesive and mechanical properties of hydrogels influence neurite extension. J Biomed Mater Res 2005; 72A: 91–97.

    CAS  Google Scholar 

  61. Downing BR, Cornwell K, Toner M, Pins GD . The influence of microtextured basal lamina analog topography on keratinocyte function and epidermal organization. J Biomed Mater Res 2005; 72A: 47–56.

    CAS  Google Scholar 

  62. Lee CR, Grodzinsky AJ, Spector M . Modulation of the contractile and biosynthetic activity of chondrocytes seeded in collagen–glycosaminoglycan matrices. Tissue Eng 2003; 9: 27–36.

    CAS  PubMed  Google Scholar 

  63. Nerem RM . Critical issues in vascular tissue engineering. Int Congr Ser 2004; 1262: 359.

    Google Scholar 

  64. Matsumura G et al. Successful application of tissue engineered vascular autografts: clinical experience. Biomaterials 2003; 24: 2303–2309.

    CAS  PubMed  Google Scholar 

  65. Neumenschwander S, Hoestrup SP . Heart valve tissue engineering. Transplant Immunol 2004; 12: 359–364.

    Google Scholar 

  66. Carmeliet P . Manipulating angiogenesis in medicine. J Intern Med 2004; 255: 538–561.

    PubMed  Google Scholar 

  67. Semino CE et al. Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three dimensional peptide scaffolds. Differentiation 2003; 71: 262–270.

    CAS  PubMed  Google Scholar 

  68. Jones JR, Hench LL . The effect of processing variables on the properties of bioactive glass foams. J Biomed Mater Res B 2004; 68B: 36–44.

    CAS  Google Scholar 

  69. Jones JR, Ahir S, Hench LL . Large scale production of 3D bioactive glass macroporous scaffolds for tisssue engineering. J Sol–Gel Sci Technol 2004; 29: 179–188.

    CAS  Google Scholar 

  70. Gough JE, Jones JR, Hench LL . Nodule formation and mineralization of human primary osteoblasts cultered on a porous bioactive glass scaffolds. Biomaterials 2004; 25: 2039–2046.

    CAS  PubMed  Google Scholar 

  71. Lenza RFS, Jones JR, Vasconcelos WL, Hench LL . In vitro release kinetics of proteins from bioactive foams. J Biomed Mater Res 2003; 67A: 121–129.

    CAS  Google Scholar 

  72. Pryce R, Hench LL . Tailoring of bioactive glasses for the release of nitric oxide as an osteogenic stimulus. J Mater Chem 2004; 14: 1–9.

    Google Scholar 

  73. Lynn A et al. Repair of defects in articular joints: prospects for material-based solutions in tissue engineering. J Bone Joint Surg (Br Ed) 2004; 86B: 1095–1101.

    Google Scholar 

  74. Sittinger M, Hutmacher DW, Risbud MV . Current strategies for cell delivery in cartilage and bone regeneration. Curr Opin Biotechnol 2004; 15: 411–418.

    CAS  PubMed  Google Scholar 

  75. Drury JL, Mooney DJ . Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 2003; 24: 4337–4351.

    CAS  PubMed  Google Scholar 

  76. Kofron MD, Li X, Laurencin CT . Protein- and gene-based tissue engineering in bone repair. Curr Opin Biotechnol 2004; 15: 399–405.

    CAS  PubMed  Google Scholar 

  77. Patel ZS, Mikos A . Angiogenesis with biomaterial-based drug and cell-delivery systems. J Biomater Sci Polym Edn 2004; 15: 701–726.

    CAS  Google Scholar 

  78. Rea SM, Bonfield W . Biocomposistes for medical applications. J Aust Ceram Soc 2004; 40: 43–57.

    CAS  Google Scholar 

  79. Lynn AK, Yannas IV, Bonfield W . Antigenicity and immunogenicity of collagen. J Biomed Mater Res B 2004; 71B: 343–354.

    CAS  Google Scholar 

  80. Ingher DE, Tensegrity II . How structural networks influence cellular information processing networks. J Cell Science 2003; 116 (Part 8): 1397–1408.

    Google Scholar 

  81. Ingher DE . Mechanochemical basis of cell and tissue regulation. The Bridge (Natl Acad Eng) 2004; 34: 4–10.

    Google Scholar 

  82. Klement BJ et al. Skeletal tissue growth, differentiation and mineralization in the NASA Rotaing Wall Vessel. Bone 2004; 34: 487–498.

    CAS  PubMed  Google Scholar 

  83. Dutt K et al. Generation of 3-D Retina-like structures from a human retinal cell line in a NASA Bioreactor. Cell Trans 2003; 12: 717–731.

    Google Scholar 

  84. Darling EM, Athanasiou KA . Articular cartilage bioreactors and bioprocesses. Tissue Eng 2003; 9: 9–26.

    CAS  PubMed  Google Scholar 

  85. Ontiveros C, McCabe LR . Simulated microgravity suppresses osteoblast phenotype, runx2 levels and AP-1 transactivation. J Cell Biochem 2003; 88: 427–437.

    CAS  PubMed  Google Scholar 

  86. Plett PA et al. Impact of modelled microgravity on migration, differentiation and cell cycle control of primitive human hematopoietic progenitor cells. Exp Hematol 2004; 32: 773–781.

    CAS  PubMed  Google Scholar 

  87. Meyers VE et al. Modelled microgravity disrupts collagen I/integrin signalling during osteoblastic differentiation of human mesenchymal stem cells. J Cell Biochem 2004; 93: 697–707.

    CAS  PubMed  Google Scholar 

  88. Shelton JC, Bader DL, Lee DA . Mechanical conditioning influences the metabolic response of cell-seeded constructs. Cells Tissues Organs 2003; 175: 140–150.

    PubMed  Google Scholar 

  89. Wang W, Vadgama P . O2 microsensors for minimally invasive tissue monitoring. J R Soc Interface 2004; 1: 109–117.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Notingher I et al. Spectroscopic study of human lung epithelial cells (A549) in culture: living cells versus dead cells. Biopolymers (Biospectroscopy) 2003; 72: 230–240.

    CAS  Google Scholar 

  91. Verrier S, Notingher I, Polak JM, Hench LL . In-situ monitoring of cell death using Raman microspectroscopy. ECSBM 10 Biopolymers 2004; 74: 157–162.

    CAS  Google Scholar 

  92. Hench LL, Notingher I . NovaTest: a biophotonics system for rapid in-vitro toxicity testing. Am Ceram Soc Bull 2004; 83: 14–15.

    Google Scholar 

  93. Notingher I et al. In-situ non-invasive discrimination between bone cell phenotypes used in tissue engineering. J Cell Biochem 2004; 92: 1180–1192.

    CAS  PubMed  Google Scholar 

  94. Notingher I, Bisson I, Polak JM, Hench LL . In-situ spectroscopic study of nucleic acids in differentiating embryonic stem cells. Vib Spectrosc 2004; 35: 199–203.

    CAS  Google Scholar 

  95. Notingher I et al. In-situ monitoring of mRNA translation in embryonic stem cells during differentiation in-vitro. Anal Chem 2004; 76: 3185–3193.

    CAS  PubMed  Google Scholar 

  96. Notingher I et al. Discrimination between ricin and sulphur mustard toxicology in vitro by Raman spectroscopy. J R Soc Interface 2004; 1: 79–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Owen CA et al. Raman spectroscopy as a tool for preliminary drug testing on human cells. J Pharm Pharmacol 2004; 56: S-51.

    Google Scholar 

  98. Notingher I, Selvakumaran J, Hench LL . New detection system for toxic agents based on continuous spectroscopic monitoring of living cells. Biosens Bioelectron 2004; 20: 780–789.

    CAS  PubMed  Google Scholar 

  99. Kostyuk O et al. Structural changes in loaded tendons can be monitored by a novel spectroscopic technique. J Physiol 2004; 554: 791–801.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Polak, J., Hench, L. Gene Therapy Progress and Prospects: In tissue engineering. Gene Ther 12, 1725–1733 (2005). https://doi.org/10.1038/sj.gt.3302651

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302651

Keywords

This article is cited by

Search

Quick links