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.

  • Article
  • Published:

Improved therapeutic potential of MSCs by genetic modification

Gene Therapy volume 25, pages 538–547 (2018)Cite this article

Subjects

Abstract

Mesenchymal stem cells (MSCs), well-studied adult stem cells in various tissues, possess multi-lineage differentiation potential and anti-inflammatory properties. MSCs have been approved to regenerate lineage-specific cells to replace injured cells in tissues. MSCs are approved to treat inflammatory diseases. With the discovery of genes important for the repair of damaged tissues, MSCs genetically modified by such genes hold improved therapeutic potential. In this review, we summarised the uses of genetically modified MSCs to treat different diseases, including bone diseases, cardiovascular diseases, autoimmune diseases, central nervous system disorders, and cancer. To better understand the exact role of genetically modified MSCs, key mechanisms determining, which genes are selected to be used for modifying MSCs and improvements in post-genetic modification are discussed. Therapeutic benefits enhanced by genetic modifications are to be documented by further clinical studies.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Caplan AI. Mesenchymal stem cells. J Orthop Res: Off Publ Orthop Res Soc. 1991;9:641–50.

    Article  CAS  Google Scholar 

  2. Kfoury Y, David TS. mesenchymal cell contributions to the stem cell niche. Cell Stem Cell. 2015;16: 239–53.

    Article  CAS  PubMed  Google Scholar 

  3. Keating A. How do mesenchymal stromal cells suppress T Cells? Cell Stem Cell. 2008;2: 106–8.

    Article  CAS  PubMed  Google Scholar 

  4. Ishikawa T, Factor VM, Marquardt JU, Raggi C, Seo D, Kitade M, et al. Hepatocyte growth factor/c-met signaling is required for stem-cell-mediated liver regeneration in mice. Hepatol (Baltim, Md). 2012;55:1215–26.

    Article  CAS  Google Scholar 

  5. Jin SZ, Meng XW, Sun X, Han MZ, Liu BR, Wang XH, et al. Hepatocyte growth factor promotes liver regeneration induced by transfusion of bone marrow mononuclear cells in a murine acute liver failure model. J hepato-Biliary-Pancreat Sci. 2011;18:397–405.

    Article  Google Scholar 

  6. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726–36.

    Article  CAS  PubMed  Google Scholar 

  7. Hernigou P, Flouzat-Lachaniette CH, Delambre J, Poignard A, Allain J, Chevallier N, et al. Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. Bone. 2015;70:102–9.

    Article  PubMed  Google Scholar 

  8. Saeed H, Ahsan M, Saleem Z, Iqtedar M, Islam M, Danish Z, et al. Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update. J Biomed Sci. 2016;23:41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhang J, Chen J. Bone tissue regeneration—Application of mesenchymal stem cells and cellular and molecular mechanisms. Curr Stem Cell Res Ther. 2017;12:357–64.

  10. Salazar VS, Gamer LW, Rosen V. BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol. 2016;12:203–21.

    Article  CAS  PubMed  Google Scholar 

  11. Pelled G, Tai K, Sheyn D, Zilberman Y, Kumbar S, Nair LS, et al. Structural and nanoindentation studies of stem cell-based tissue-engineered bone. J Biomech. 2007;40:399–411.

    Article  PubMed  Google Scholar 

  12. He X, Dziak R, Mao K, Genco R, Swihart M, Li C, et al. Integration of a novel injectable nano calcium sulfate/alginate scaffold and BMP2 gene-modified mesenchymal stem cells for bone regeneration. Tissue Eng Part A. 2013;19:508–18.

    Article  CAS  PubMed  Google Scholar 

  13. Tai K, Pelled G, Sheyn D, Bershteyn A, Han L, Kallai I, et al. Nanobiomechanics of repair bone regenerated by genetically modified mesenchymal stem cells. Tissue Eng Part A. 2008;14:1709–20.

    Article  CAS  PubMed  Google Scholar 

  14. Ding HF, Liu R, Li BG, Lou JR, Dai KR, Tang TT. Biologic effect and immunoisolating behavior of BMP-2 gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules. Biochem Biophys Res Commun. 2007;362:923–7.

    Article  CAS  PubMed  Google Scholar 

  15. Vural AC, Odabas S, Korkusuz P, Yar Saglam AS, Bilgic E, Cavusoglu T, et al. Cranial bone regeneration via BMP-2 encoding mesenchymal stem cells. Artif Cells Nanomed Biotechnol. 2017;45:544–50.

    Article  CAS  PubMed  Google Scholar 

  16. Peterson B, Zhang J, Iglesias R, Kabo M, Hedrick M, Benhaim P, et al. Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. Tiss Eng. 2005;11:120–9.

    Article  CAS  Google Scholar 

  17. Chen W, Wahl SM. TGF-beta: the missing link in CD4+CD25+regulatory T cell-mediated immunosuppression. Cytokine Growth Factor Rev. 2003;14:85–9.

    Article  CAS  PubMed  Google Scholar 

  18. Guo X, Zheng Q, Yang S, Shao Z, Yuan Q, Pan Z, et al. Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor beta1 gene. Biomed Mater. 2006;1:206–15.

    Article  CAS  PubMed  Google Scholar 

  19. Xie Q, Wang Z, Zhou H, Yu Z, Huang Y, Sun H, et al. The role of miR-135-modified adipose-derived mesenchymal stem cells in bone regeneration. Biomaterials. 2016;75:279–94.

    Article  CAS  PubMed  Google Scholar 

  20. Lapidot T, Kollet O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia. 2002;16:1992–2003.

    Article  CAS  PubMed  Google Scholar 

  21. Lien CY, Chih-Yuan HoK, Lee OK, Blunn GW, Su Y. Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells. J Bone Mineral Res: Off J Am Soc Bone Mineral Res. 2009;24:837–48.

    Article  CAS  Google Scholar 

  22. Koninckx R, Hensen K, Daniels A, Moreels M, Lambrichts I, Jongen H, et al. Human bone marrow stem cells co-cultured with neonatal rat cardiomyocytes display limited cardiomyogenic plasticity. Cytotherapy. 2009;11:778–92.

    Article  CAS  PubMed  Google Scholar 

  23. Gersh BJ. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Yearb Cardiol. 2010;2010:389–91.

    Article  Google Scholar 

  24. Cashman TJ, Gouon-Evans V, Costa KD. Mesenchymal stem cells for cardiac therapy: practical challenges and potential mechanisms. Stem Cell Rev. 2013;9:254–65.

    Article  CAS  PubMed Central  Google Scholar 

  25. Griffin M, Greiser U, Barry F, O’Brien T, Ritter T. Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease. Discov Med. 2010;9:219–23.

    PubMed  Google Scholar 

  26. Kim SH, Moon HH, Kim HA, Hwang KC, Lee M, Choi D. Hypoxia-inducible vascular endothelial growth factor-engineered mesenchymal stem cells prevent myocardial ischemic injury. Mol Ther: J Am Soc Gene Ther. 2011;19:741–50.

    Article  CAS  Google Scholar 

  27. Zeng B, Ren X, Lin G, Zhu C, Chen H, Yin J, et al. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement. Cell Biol Int. 2008;32:1256–64.

    Article  CAS  PubMed  Google Scholar 

  28. Shu T, Zeng B, Ren X, Li Y. HO-1 modified mesenchymal stem cells modulate MMPs/TIMPs system and adverse remodeling in infarcted myocardium. Tissue Cell. 2010;42:217–22.

    Article  CAS  PubMed  Google Scholar 

  29. Sun L, Cui M, Wang Z, Feng X, Mao J, Chen P, et al. Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction. Biochem Biophys Res Commun. 2007;357:779–84.

    Article  CAS  PubMed  Google Scholar 

  30. Liu XH, Bai CG, Xu ZY, Huang SD, Yuan Y, Gong DJ, et al. Therapeutic potential of angiogenin modified mesenchymal stem cells: angiogenin improves mesenchymal stem cells survival under hypoxia and enhances vasculogenesis in myocardial infarction. Microvasc Res. 2008;76:23–30.

    Article  CAS  PubMed  Google Scholar 

  31. Cheng Z, Ou L, Zhou X, Li F, Jia X, Zhang Y, et al. Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther: J Am Soc Gene Ther. 2008;16:571–9.

    Article  CAS  Google Scholar 

  32. Cho YH, Cha MJ, Song BW, Kim IK, Song H, Chang W, et al. Enhancement of MSC adhesion and therapeutic efficiency in ischemic heart using lentivirus delivery with periostin. Biomaterials. 2012;33:1376–85.

    Article  CAS  PubMed  Google Scholar 

  33. Liang Y, Lin Q, Zhu J, Li X, Fu Y, Zou X, et al. The caspase-8 shRNA-modified mesenchymal stem cells improve the function of infarcted heart. Mol Cell Biochem. 2014;397:7–16.

    Article  CAS  PubMed  Google Scholar 

  34. Gao L, Bledsoe G, Yin H, Shen B, Chao L, Chao J. Tissue kallikrein-modified mesenchymal stem cells provide enhanced protection against ischemic cardiac injury after myocardial infarction. Circ J: Off J Jpn Circ Soc. 2013;77:2134–44.

    Article  CAS  Google Scholar 

  35. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11:367–8.

    Article  CAS  PubMed  Google Scholar 

  36. Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, et al. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci USA. 2007;104:1643–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Najar M, Raicevic G, Crompot E, Fayyad-Kazan H, Bron D, Toungouz M, et al. The Immunomodulatory Potential of Mesenchymal Stromal Cells: A Story of a Regulatory Network. J Immunother (Hagerstown, Md: 1997). 2016;39:45–59.

    CAS  Google Scholar 

  38. Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, et al. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 2014;6:552–70.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012;12:383–96.

    Article  CAS  PubMed  Google Scholar 

  40. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–86.

    Article  CAS  PubMed  Google Scholar 

  41. Bao C, Guo J, Lin G, Hu M, Hu Z. TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. Scand Cardiovasc J: SCJ. 2008;42:56–62.

    Article  CAS  PubMed  Google Scholar 

  42. Hu J, Li H, Chi G, Yang Z, Zhao Y, Liu W, et al. IL-1RA gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules could alleviate rheumatoid arthritis. Int J Clin Exp Med. 2015;8:706–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. He T, Chi G, Tian B, Tang T, Dai K. Lentivirus transduced interleukin-1 receptor antagonist gene expression in murine bone marrow-derived mesenchymal stem cells in vitro. Mol Med Rep. 2015;12:4063–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Xia Q, Zhu S, Wu Y, Wang J, Cai Y, Chen P, et al. Intra-articular transplantation of atsttrin-transduced mesenchymal stem cells ameliorate osteoarthritis development. Stem Cells Transl Med. 2015;4:523–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cao H, Chu Y, Zhu H, Sun J, Pu Y, Gao Z, et al. Characterization of immortalized mesenchymal stem cells derived from foetal porcine pancreas. Cell Prolif. 2011;44:19–32.

    Article  CAS  PubMed  Google Scholar 

  46. Narang AS, Sabek O, Gaber AO, Mahato RI. Co-expression of vascular endothelial growth factor and interleukin-1 receptor antagonist improves human islet survival and function. Pharm Res. 2006;23:1970–82.

    Article  CAS  PubMed  Google Scholar 

  47. Panakanti R, Mahato RI. Bipartite adenoviral vector encoding hHGF and hIL-1Ra for improved human islet transplantation. Pharm Res. 2009;26:587–96.

    Article  CAS  PubMed  Google Scholar 

  48. Barzelay A, Ben-Shoshan J, Entin-Meer M, Maysel-Auslender S, Afek A, Barshack I, et al. A potential role for islet-1 in post-natal angiogenesis and vasculogenesis. Thromb Haemost. 2010;103:188–97.

    Article  CAS  PubMed  Google Scholar 

  49. Li Y, Li W, Liu C, Yan M, Raman I, Du Y, et al. Delivering oxidation resistance-1 (OXR1) to mouse kidney by genetic modified mesenchymal stem cells exhibited enhanced protection against nephrotoxic serum induced renal injury and lupus nephritis. J Stem Cell Res Ther. 2014;4:1–12.

  50. Zeng X, Qiu XC, Ma YH, Duan JJ, Chen YF, Gu HY, et al. Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection. Biomaterials. 2015;53:184–201.

    Article  CAS  PubMed  Google Scholar 

  51. Ng TK, Fortino VR, Pelaez D, Cheung HS. Progress of mesenchymal stem cell therapy for neural and retinal diseases. World J Stem Cells. 2014;6:111–9.

    Article  PubMed  PubMed Central  Google Scholar 

  52. van Velthoven CT, Braccioli L, Willemen HL, Kavelaars A, Heijnen CJ. Therapeutic potential of genetically modified mesenchymal stem cells after neonatal hypoxic-ischemic brain damage. Mol Ther: J Am Soc Gene Ther. 2014;22:645–54.

    Article  CAS  Google Scholar 

  53. Rooney GE, Moran C, McMahon SS, Ritter T, Maenz M, Flugel A, et al. Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid (PLGA) substrate. Tissue Eng Part A. 2008;14:681–90.

    Article  CAS  PubMed  Google Scholar 

  54. Zhang YQ, He LM, Xing B, Zeng X, Zeng CG, Zhang W, et al. Neurotrophin-3 gene-modified Schwann cells promote TrkC gene-modified mesenchymal stem cells to differentiate into neuron-like cells in poly(lactic-acid-co-glycolic acid) multiple-channel conduit. Cells Tissues Organs. 2012;195:313–22.

    Article  CAS  PubMed  Google Scholar 

  55. Zhang YJ, Zhang W, Lin CG, Ding Y, Huang SF, Wu JL, et al. Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats. J Neurol Sci. 2012;313:64–74.

    Article  CAS  PubMed  Google Scholar 

  56. Wyse RD, Dunbar GL, Rossignol J. Use of genetically modified mesenchymal stem cells to treat neurodegenerative diseases. Int J Mol Sci. 2014;15:1719–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhang YQ, Zeng X, He LM, Ding Y, Li Y, Zeng YS. NT-3 gene modified Schwann cells promote TrkC gene modified mesenchymal stem cells to differentiate into neuron-like cells in vitro. Anat Sci Int. 2010;85:61–7.

    Article  CAS  PubMed  Google Scholar 

  58. Ding Y, Zhang RY, He B, Liu Z, Zhang K, Ruan JW, et al. Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats. Sci Rep. 2015;5:9133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kumagai G, Tsoulfas P, Toh S, McNiece I, Bramlett HM, Dietrich WD. Genetically modified mesenchymal stem cells (MSCs) promote axonal regeneration and prevent hypersensitivity after spinal cord injury. Exp Neurol. 2013;248:369–80.

    Article  CAS  PubMed  Google Scholar 

  60. Skaper SD. The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol (Clifton, N J). 2012;846:1–12.

    Article  CAS  Google Scholar 

  61. Azanchi R, Bernal G, Gupta R, Keirstead HS. Combined demyelination plus Schwann cell transplantation therapy increases spread of cells and axonal regeneration following contusion injury. J Neurotrauma. 2004;21:775–88.

    Article  PubMed  Google Scholar 

  62. Sheyn D, Ruthemann M, Mizrahi O, Kallai I, Zilberman Y, Tawackoli W, et al. Genetically modified mesenchymal stem cells induce mechanically stable posterior spine fusion. Tissue Eng Part A. 2010;16:3679–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shi D, Chen G, Lv L, Li L, Wei D, Gu P, et al. The effect of lentivirus-mediated TH and GDNF genetic engineering mesenchymal stem cells on Parkinson’s disease rat model. Neurol Sci: Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2011;32:41–51.

    Article  CAS  Google Scholar 

  64. Gwendal L, Paula YL. Recent discoveries concerning the tumor - mesenchymal stem cell interactions. Biochim Biophys Acta. 2016;1866:290–9.

    CAS  Google Scholar 

  65. Niess H, von Einem JC, Thomas MN, Michl M, Angele MK, Huss R, et al. Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial. BMC Cancer. 2015;15:237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Norozi F, Ahmadzadeh A, Shahrabi S, Vosoughi T, Saki N. Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells. Tumour Biol. 2016;37:11679–89.

    Article  CAS  PubMed  Google Scholar 

  67. Vianello F, Villanova F, Tisato V, Lymperi S, Ho KK, Gomes AR, et al. Bone marrow mesenchymal stromal cells non-selectively protect chronic myeloid leukemia cells from imatinib-induced apoptosis via the CXCR4/CXCL12 axis. Haematologica. 2010;95:1081–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 2009;9:285–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zielske SP, Livant DL, Lawrence TS. Radiation increases invasion of gene-modified mesenchymal stem cells into tumors. Int J Radiat Oncol Biol Phys. 2009;75:843–53.

    Article  CAS  PubMed  Google Scholar 

  70. Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S, et al. BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. Mol Ther: J Am Soc Gene Ther. 2004;9:189–97.

    Article  CAS  Google Scholar 

  71. Piao W, Wang H, Inoue M, Hasegawa M, Hamada H, Huang J. Transplantation of Sendai viral angiopoietin-1-modified mesenchymal stem cells for ischemic limb disease. Angiogenesis. 2010;13:203–10.

    Article  CAS  PubMed  Google Scholar 

  72. Xue J, Li X, Lu Y, Gan L, Zhou L, Wang Y, et al. Gene-modified mesenchymal stem cells protect against radiation-induced lung injury. Mol Ther: J Am Soc Gene Ther. 2013;21:456–65.

    Article  CAS  Google Scholar 

  73. Li J, Zheng CQ, Li Y, Yang C, Lin H, Duan HG. Hepatocyte growth factor gene-modified mesenchymal stem cells augment sinonasal wound healing. Stem Cells Dev. 2015;24:1817–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Harper MM, Adamson L, Blits B, Bunge MB, Grozdanic SD, Sakaguchi DS. Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells. Exp Eye Res. 2009;89:538–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chen YB, Lan YW, Chen LG, Huang TT, Choo KB, Cheng WT, et al. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model. Cell Stress Chaperon-. 2015;20:979–89.

    Article  CAS  Google Scholar 

  76. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003;302:415–9.

    Article  CAS  PubMed  Google Scholar 

  77. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348:255–6.

    Article  PubMed  Google Scholar 

  78. Schmidt M, Carbonaro DA, Speckmann C, Wissler M, Bohnsack J, Elder M, et al. Clonality analysis after retroviral-mediated gene transfer to CD34+cells from the cord blood of ADA-deficient SCID neonates. Nat Med. 2003;9:463–8.

    Article  CAS  PubMed  Google Scholar 

  79. Kurtzberg J, Prockop S, Teira P, Bittencourt H, Lewis V, Chan KW, et al. Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biol Blood Marrow Transplant. 2014;20:229–35.

    Article  PubMed  Google Scholar 

  80. Kumar S, Nagy TR, Ponnazhagan S. Therapeutic potential of genetically modified adult stem cells for osteopenia. Gene Ther. 2010;17:105–16.

    Article  CAS  PubMed  Google Scholar 

  81. Fernandes G, Wang C, Yuan X, Liu Z, Dziak R, Yang S. Combination of controlled release platelet-rich plasma alginate beads and bone morphogenetic protein-2 genetically modified mesenchymal stem cells for bone regeneration. J Periodontol. 2016;87:470–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Xu L, Huang S, Hou Y, Liu Y, Ni M, Meng F, et al. Sox11-modified mesenchymal stem cells (MSCs) accelerate bone fracture healing: Sox11 regulates differentiation and migration of MSCs. FASEB J: Off Publ Fed Am Soc Exp Biol. 2015;29:1143–52.

    Article  CAS  Google Scholar 

  83. Payne NL, Dantanarayana A, Sun G, Moussa L, Caine S, McDonald C, et al. Early intervention with gene-modified mesenchymal stem cells overexpressing interleukin-4 enhances anti-inflammatory responses and functional recovery in experimental autoimmune demyelination. Cell Adhes Migr. 2012;6:179–89.

    Article  Google Scholar 

  84. Yin X, Xu H, Jiang Y, Deng W, Wu Z, Xiang H, et al. The effect of lentivirus-mediated PSPN genetic engineering bone marrow mesenchymal stem cells on Parkinson’s disease rat model. PLoS ONE. 2014;9:e105118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ciavarella S, Grisendi G, Dominici M, Tucci M, Brunetti O, Dammacco F, et al. In vitro anti-myeloma activity of TRAIL-expressing adipose-derived mesenchymal stem cells. Br J Haematol. 2012;157:586–98.

    Article  CAS  PubMed  Google Scholar 

  86. Xu G, Jiang XD, Xu Y, Zhang J, Huang FH, Chen ZZ, et al. Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats. Cell Biol Int. 2009;33:466–74.

    Article  CAS  PubMed  Google Scholar 

  87. Dembinski JL, Wilson SM, Spaeth EL, Studeny M, Zompetta C, Samudio I, et al. Tumor stroma engraftment of gene-modified mesenchymal stem cells as anti-tumor therapy against ovarian cancer. Cytotherapy. 2013;15:20–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nakamura K, Ito Y, Kawano Y, Kurozumi K, Kobune M, Tsuda H, et al. Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Ther. 2004;11:1155–64.

    Article  CAS  PubMed  Google Scholar 

  89. Wang H, Yang YF, Zhao L, Xiao FJ, Zhang QW, Wen ML, et al. Hepatocyte growth factor gene-modified mesenchymal stem cells reduce radiation-induced lung injury. Hum Gene Ther. 2013;24:343–53.

    Article  CAS  PubMed  Google Scholar 

  90. Snow-Lisy DC, Diaz EC, Bury MI, Fuller NJ, Hannick JH, Ahmad N, et al. The role of genetically modified mesenchymal stem cells in urinary bladder regeneration. PLoS ONE. 2015;10:e0138643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work is supported by the National High-tech R&D programme (863 Programme) 2014AA020704 and the National Natural and Scientific Foundation of China, 81400057/H0111, 81572981/H1611, 81123003/H1604, 81201789/H1611 81672397/H1617.

Author information

Authors and Affiliations

  1. Department of Emergency, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China

    Wei Wei, Yong Huang, Dan Li & Wei Wang

  2. Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China

    Yong Huang, Dan Li, Hong-Feng Gou & Wei Wang

Authors
  1. Wei Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong-Feng Gou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, W., Huang, Y., Li, D. et al. Improved therapeutic potential of MSCs by genetic modification. Gene Ther 25, 538–547 (2018). https://doi.org/10.1038/s41434-018-0041-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41434-018-0041-8

This article is cited by

Search

Advanced search

Quick links