New Tools in Regenerative Medicine: Gene Therapy

  • Miguel Muñoz Ruiz
  • José R. RegueiroEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 741)


Gene therapy aims to transfer genetic material into cells to provide them with new functions. A gene transfer agent has to be safe, capable of expressing the desired gene for a sustained period of time in a sufficiently large population of cells to produce a biological effect. Identifying a gene transfer tool that meets all of these criteria has proven to be a difficult objective. Viral and nonviral vectors, in vivo, ex vivo and in situ strategies co-exist at present, although ex vivo lenti- or retroviral vectors are presently the most popular.

Natural stem cells (from embryonic, hematopoietic, mesenchymal, or adult tissues) or induced progenitor stem (iPS) cells can be modified by gene therapy for use in regenerative medicine. Among them, hematopoietic stem cells have shown clear clinical benefit, but iPS cells hold humongous potential with no ethical concerns.


Stem Cell Gene Therapy Mesenchymal Stem Cell Regenerative Medicine Chronic Granulomatous Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jopling C, Boue S, Izpisua Belmonted JC. Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol. 2011 Feb;12(2):79–89.PubMedCrossRefGoogle Scholar
  2. 2.
    Noguchi P. Risks and benefits of gene therapy. N Engl J Med 2003; 348:193–194.PubMedCrossRefGoogle Scholar
  3. 3.
    Urnov FD, Miller JC, Lee YL et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 2005; 435:646–651.PubMedCrossRefGoogle Scholar
  4. 4.
    Chan PP, Glazer PM. Triplex DNA: Fundamentals, advances, and potential applications for gene therapy. J Mol Med 1997; 75:267–282.PubMedCrossRefGoogle Scholar
  5. 5.
    Berns A. Good news for gene therapy. N Engl J Med 2004; 350(16):1679–1680.PubMedCrossRefGoogle Scholar
  6. 6.
    Gene therapy progress and prospects. Special tissue. Gene Ther 2004; 11.Google Scholar
  7. 7.
    Räty JK, Lesch HP, Wirth T et al. Improving safety of gene therapy. Curr Drug Saf 2008; 3(1):46–53.PubMedCrossRefGoogle Scholar
  8. 8.
    Douglas KL. Toward development of artificial viruses for gene therapy: a comparative evaluation of viral and non-viral transfection. Biotechnol Prog 2008; 24:871–883.PubMedGoogle Scholar
  9. 9.
    Foldvari M, Babiuk S, Badea I. DNA delivery for vaccination and therapeutics through the skin. Curr Drug Deliv 2006; 3(1):17–28.PubMedCrossRefGoogle Scholar
  10. 10.
    Acsadi G, Dickson G, Love DR et al. Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 1991; 29:757–758.Google Scholar
  11. 11.
    Ahrlund-Richter L, De Luca M, Marshak DR et al. Isolation and production of cells suitable for human therapy: challenges ahead. Cell Stem Cell 2009; 4:20–26.PubMedCrossRefGoogle Scholar
  12. 12.
    Cuende N, Izeta A. Clinical translation of stem cell therapies: a bridgeable gap. Cell Stem Cell 2010; 6(6):508–512.PubMedCrossRefGoogle Scholar
  13. 13.
    Alexander BL, Ali RR, Alton EW et al. Progress and prospects: gene therapy clinical trials (part 1). Gene Ther 2007; 14(20):1439–1447.PubMedCrossRefGoogle Scholar
  14. 14.
    Gatti RA, Meuwissen HJ, Allen HD et al. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 1968; 2:1366–1369.PubMedCrossRefGoogle Scholar
  15. 15.
    Unger C, Kärner E, Treschow A et al. Lentiviral-mediated HoxB4 expression in human embryonic stem cells initiates early hematopoiesis in a dose-dependent manner but does not promote myeloid differentiation. Stem Cells. 2008; 26:2455–2466.PubMedCrossRefGoogle Scholar
  16. 16.
    Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131:861–872.PubMedCrossRefGoogle Scholar
  17. 17.
    Hadjantonakis A, Papaioannou V. The stem cells of early embryos. Differentiation 2001; 68:159–166.PubMedCrossRefGoogle Scholar
  18. 18.
    Kucerova L, Altanerova V, Matuskova M et al. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Research. 2007; 67:6304–6313.PubMedCrossRefGoogle Scholar
  19. 19.
    Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411):143–147.PubMedCrossRefGoogle Scholar
  20. 20.
    Kumar S, Chanda D, Ponnazhagan S. Therapeutic potential of genetically modified mesenchymal stem cells. Gene Ther 2008; 15(10):711–715.PubMedCrossRefGoogle Scholar
  21. 21.
    Strom S, Fisher R. Hepatocyte transplantation: new possibilities for therapy. Gastroenterology 2003; 124:568–571.PubMedCrossRefGoogle Scholar
  22. 22.
    Rideout WM 3rd, Hochedlinger K, Kyba M et al. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 2002; 109:17–27.PubMedCrossRefGoogle Scholar
  23. 23.
    Ott MG, Schmidt M, Schwarzwaelder K et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med 2006; 12:401–409.PubMedCrossRefGoogle Scholar
  24. 24.
    Podsakoff GM, Engel BC, Carbonaro DA et al. Selective survival of peripheral blood lymphocytes in children with HIV-1 following delivery of an anti-HIV gene to bone marrow CD34(+) cells. Mol Ther 2005; 12:77–86.PubMedCrossRefGoogle Scholar
  25. 25.
    Weiss ML, Troyer DL. Stem cells in the umbilical cord. Stem Cell Rev 2006; 2:155–162. Review.PubMedCrossRefGoogle Scholar
  26. 26.
    Le Blanc K, Rasmusson I, Sundberg B et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363:1439–1441.PubMedCrossRefGoogle Scholar
  27. 27.
    Studeny M, Marini FC, Dembinski JL et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004; 96:1593–1603.PubMedCrossRefGoogle Scholar
  28. 28.
    Kumar S, Ponnazhagan S. Bone homing of mesenchymal stem cells by ectopic alpha 4 integrin expression. FASEB J 2007; 21:3917–3927.PubMedCrossRefGoogle Scholar
  29. 29.
    Hachiya A, Sriwiriyanont P, Patel A et al. Gene transfer in human skin with different pseudotyped HIV-based vectors. Gene Ther 2007; 14:648–656.PubMedCrossRefGoogle Scholar
  30. 30.
    Mavilio F, Pellegrini G, Ferrari S et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 2006; 12:1397–1402.PubMedCrossRefGoogle Scholar
  31. 31.
    Raya A, Rodriguez-Piza I, Guenechea G et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 2009; 460:53–59.PubMedCrossRefGoogle Scholar
  32. 32.
    Sun N, Longaker MT, Wu JC. Human iPS cell-based therapy. Considerations before clinical applications. Cell Cycle 2010; 9:880–885.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  1. 1.Department of ImmunologyUniversidad Complutense de MadridMadridSpain

Personalised recommendations