title: Genetic engineering of mesenchymal stem cells and its application in human disease therapy.
abstract: The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Hodgkinson
authors.forename: José A
authors.initials: JA
authors.lastname: Gomez
authors.forename: Maria
authors.initials: M
authors.lastname: Mirotsou
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Dzau
mesh_terms: D016026:Bone Marrow Transplantation; D002318:Cardiovascular Diseases / Q000628:therapy; D002454:Cell Differentiation; D002986:Clinical Trials as Topic; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009369:Neoplasms / Q000628:therapy; D009422:Nervous System Diseases / Q000628:therapy; D010012:Osteogenesis; D051437:Renal Insufficiency / Q000628:therapy
references.citation: J Am Soc Nephrol. 2006 Jun;17(6):1576-84
references.pmid: 16672321
references.citation: J Int Med Res. 2009 Jan-Feb;37(1):68-78
references.pmid: 19215675
references.citation: Breast Cancer Res Treat. 2007 Oct;105(2):157-67
references.pmid: 17221158
references.citation: J Biomed Mater Res. 2000 Mar 5;49(3):328-37
references.pmid: 10602065
references.citation: Stem Cells. 2007 Jul;25(7):1618-26
references.pmid: 17412895
references.citation: J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86
references.pmid: 19958962
references.citation: Nat Med. 2005 Apr;11(4):367-8
references.pmid: 15812508
references.citation: Biochem Biophys Res Commun. 2009 Dec 18;390(3):902-7
references.pmid: 19852944
references.citation: Cell Transplant. 2000 Jan-Feb;9(1):55-64
references.pmid: 10784067
references.citation: Stem Cells. 2008 Aug;26(8):2173-82
references.pmid: 18511601
references.citation: FASEB J. 2006 Feb;20(2):207-16
references.pmid: 16449792
references.citation: Mol Cells. 2005 Jun 30;19(3):402-7
references.pmid: 15995358
references.citation: J Cell Physiol. 2009 Feb;218(2):237-45
references.pmid: 18792913
references.citation: Eur Heart J. 2009 Dec;30(24):2978-84
references.pmid: 19773226
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H48-59
references.pmid: 17322421
references.citation: J Mol Cell Cardiol. 2009 Mar;46(3):370-7
references.pmid: 19109969
references.citation: Bone Marrow Transplant. 2002 Aug;30(4):215-22
references.pmid: 12203137
references.citation: Catheter Cardiovasc Interv. 2005 Jul;65(3):321-9
references.pmid: 15954106
references.citation: Pigment Cell Melanoma Res. 2010 Jun;23(3):312-3
references.pmid: 20415714
references.citation: Pharmacol Res. 2008 Aug;58(2):88-111
references.pmid: 18620057
references.citation: Cancer Res. 2009 May 15;69(10):4134-42
references.pmid: 19435900
references.citation: Cell Biol Int. 2009 Apr;33(4):466-74
references.pmid: 18725309
references.citation: J Neurosci Res. 2000 Aug 15;61(4):364-70
references.pmid: 10931522
references.citation: J Bone Miner Res. 2003 Apr;18(4):716-22
references.pmid: 12674332
references.citation: J Bone Joint Surg Am. 1998 Jul;80(7):985-96
references.pmid: 9698003
references.citation: Methods Mol Biol. 2010;660:65-84
references.pmid: 20680813
references.citation: Cell. 2005 May 6;121(3):335-48
references.pmid: 15882617
references.citation: Mol Ther. 2008 Mar;16(3):571-9
references.pmid: 18253156
references.citation: J Mol Med (Berl). 2008 Nov;86(11):1221-32
references.pmid: 18690419
references.citation: Gene Ther. 2004 Jul;11(14):1155-64
references.pmid: 15141157
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1643-8
references.pmid: 17251350
references.citation: Rejuvenation Res. 2009 Oct;12(5):359-66
references.pmid: 19929258
references.citation: J Biol Chem. 2009 Mar 20;284(12):7853-65
references.pmid: 19164288
references.citation: Biochem J. 2010 Apr 28;428(1):11-23
references.pmid: 20423328
references.citation: Eur J Gastroenterol Hepatol. 2009 Oct;21(10):1199-205
references.pmid: 19455046
references.citation: Exp Hematol. 2004 Dec;32(12):1238-45
references.pmid: 15588948
references.citation: Exp Hematol. 2006 Nov;34(11):1563-72
references.pmid: 17046576
references.citation: Ann Neurol. 2005 Jun;57(6):874-82
references.pmid: 15929052
references.citation: Transl Res. 2010 Feb;155(2):62-70
references.pmid: 20129486
references.citation: Nature. 2004 Apr 8;428(6983):668-73
references.pmid: 15034594
references.citation: Cancer Res. 2007 Nov 1;67(21):10099-102
references.pmid: 17974948
references.citation: Hematol Oncol. 2006 Sep;24(3):151-8
references.pmid: 16700092
references.citation: Exp Neurol. 2010 May;223(1):229-37
references.pmid: 19682989
references.citation: FASEB J. 2007 Oct;21(12):3197-207
references.pmid: 17496162
references.citation: Leukemia. 2008 Mar;22(3):593-9
references.pmid: 18185520
references.citation: J Biol Chem. 1996 May 31;271(22):12687-90
references.pmid: 8663110
references.citation: Neuro Endocrinol Lett. 2006 Dec;27 Suppl 2:134-7
references.pmid: 17159798
references.citation: Biochem Biophys Res Commun. 2001 Mar 23;282(1):148-52
references.pmid: 11263984
references.citation: Clin Cancer Res. 2009 Aug 1;15(15):4925-34
references.pmid: 19638465
references.citation: Circulation. 2005 May 3;111(17):2198-202
references.pmid: 15851598
references.citation: Expert Rev Clin Immunol. 2010 Mar;6(2):211-8
references.pmid: 20402384
references.citation: Cell Stem Cell. 2009 Apr 3;4(4):313-23
references.pmid: 19341621
references.citation: Circulation. 2007 Aug 7;116(6):654-63
references.pmid: 17646584
references.citation: Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1897-908
references.pmid: 18566299
references.citation: Hum Gene Ther. 2007 Jul;18(7):627-41
references.pmid: 17604566
references.citation: Mol Ther. 2003 Sep;8(3):467-74
references.pmid: 12946320
references.citation: Exp Biol Med (Maywood). 2008 Jul;233(7):901-13
references.pmid: 18445775
references.citation: J Urol. 2010 Jul;184(1):26-33
references.pmid: 20478602
references.citation: Biochem Biophys Res Commun. 2007 May 18;356(4):836-42
references.pmid: 17391646
references.citation: Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1393-405
references.pmid: 16387794
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1168-73
references.pmid: 15831811
references.citation: Circ Res. 2009 May 22;104(10):1209-16
references.pmid: 19407239
references.citation: Circulation. 2003 May 13;107(18):2294-302
references.pmid: 12707230
references.citation: Arch Med Res. 2006 Nov;37(8):1010-4
references.pmid: 17045119
references.citation: J Neurol Sci. 2001 Aug 15;189(1-2):49-57
references.pmid: 11535233
references.citation: Nat Clin Pract Cardiovasc Med. 2004 Dec;1(2):90-5
references.pmid: 16265312
references.citation: J Cell Physiol. 2008 Aug;216(2):458-68
references.pmid: 18288639
references.citation: Circ Res. 2008 Nov 21;103(11):1300-8
references.pmid: 18948617
references.citation: Circulation. 2002 Dec 10;106(24):3009-17
references.pmid: 12473544
references.citation: Angiology. 2010 Aug;61(6):551-6
references.pmid: 20498146
references.citation: Stroke. 2002 Sep;33(9):2270-8
references.pmid: 12215598
references.citation: Expert Opin Biol Ther. 2010 Mar;10(3):321-35
references.pmid: 20132055
references.citation: Bone Marrow Transplant. 2008 Oct;42 Suppl 2:S60-6
references.pmid: 18978747
references.citation: Biochem Biophys Res Commun. 2005 Jan 21;326(3):527-38
references.pmid: 15596132
references.citation: J Neurosci. 2002 Aug 1;22(15):6623-30
references.pmid: 12151541
references.citation: Stem Cells. 2007 Jul;25(7):1737-45
references.pmid: 17395768
references.citation: Circulation. 2009 Nov 3;120(18):1800-13
references.pmid: 19841301
references.citation: Ann Thorac Surg. 2009 Mar;87(3):812-9
references.pmid: 19231395
references.citation: Int J Colorectal Dis. 2009 Jan;24(1):27-30
references.pmid: 18696086
references.citation: Heart. 2009 Jun;95(12):1012-8
references.pmid: 19304668
references.citation: Mediators Inflamm. 2010;2010:865601
references.pmid: 20628526
references.citation: Stem Cells. 2008 Sep;26(9):2332-8
references.pmid: 18617688
references.citation: Cancer Res. 2005 Apr 15;65(8):3307-18
references.pmid: 15833864
references.citation: Circulation. 2001 Sep 18;104(12 Suppl 1):I218-22
references.pmid: 11568059
references.citation: Transplantation. 2003 Oct 27;76(8):1208-13
references.pmid: 14578755
references.citation: Cell Mol Life Sci. 1999 Apr;55(4):663-7
references.pmid: 10357234
references.citation: Mol Ther. 2006 Dec;14(6):840-50
references.pmid: 16965940
references.citation: Brain Res. 2006 Dec 6;1123(1):27-33
references.pmid: 17064670
references.citation: Circ Res. 2009 May 22;104(10):1133-5
references.pmid: 19461103
references.citation: J Neurosci Res. 2003 Sep 15;73(6):778-86
references.pmid: 12949903
references.citation: Lancet. 2008 May 10;371(9624):1579-86
references.pmid: 18468541
references.citation: Nature. 2007 Oct 4;449(7162):557-63
references.pmid: 17914389
references.citation: Blood. 2001 Mar 1;97(5):1227-31
references.pmid: 11222364
references.citation: Mol Ther. 2004 Feb;9(2):189-97
references.pmid: 14759803
references.citation: Discov Med. 2010 Mar;9(46):219-23
references.pmid: 20350488
references.citation: Cancer Res. 2002 Jul 1;62(13):3603-8
references.pmid: 12097260
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1503-15
references.pmid: 19759338
references.citation: Mol Biol Cell. 2007 Aug;18(8):2873-82
references.pmid: 17507648
references.citation: Curr Opin Rheumatol. 2007 Nov;19(6):604-10
references.pmid: 17917542
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):301-13
references.pmid: 18786417
references.citation: Cell Biol Int. 2008 Oct;32(10):1256-64
references.pmid: 18692581
references.citation: Cytotherapy. 2006;8(3):202-9
references.pmid: 16793729
references.citation: Biomaterials. 2008 Jul;29(21):3053-61
references.pmid: 18433864
references.citation: Lancet. 2004 Jul 10-16;364(9429):141-8
references.pmid: 15246726
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3317-22
references.pmid: 19805054
references.citation: Can J Cardiol. 2007 Sep;23(11):891-8
references.pmid: 17876381
references.citation: Clin Cancer Res. 2007 Sep 1;13(17):5020-7
references.pmid: 17785552
references.citation: J Cell Mol Med. 2008 Oct;12(5B):1795-810
references.pmid: 18684237
references.citation: Stem Cells. 2007 Mar;25(3):655-63
references.pmid: 17124008
references.citation: Eur J Heart Fail. 2009 Nov;11(11):1023-30
references.pmid: 19875403
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: Stem Cells. 2007 Feb;25(2):520-8
references.pmid: 17053212
references.citation: Blood. 2006 Jan 1;107(1):367-72
references.pmid: 16141348
references.citation: J Mol Cell Cardiol. 2008 Oct;45(4):514-22
references.pmid: 18304573
references.citation: Chin Med J (Engl). 2005 Feb 20;118(4):281-8
references.pmid: 15740665
references.citation: Cell Transplant. 2007;16(9):879-86
references.pmid: 18293886
references.citation: Circ Res. 2008 Jul 18;103(2):203-11
references.pmid: 18566343
references.citation: Lancet. 2003 Jan 4;361(9351):45-6
references.pmid: 12517467
references.citation: J Cell Biochem. 2010 Oct 1;111(2):249-57
references.pmid: 20506559
references.citation: J Biol Chem. 2007 Oct 19;282(42):30938-48
references.pmid: 17720811
references.citation: Circ Res. 2010 Jun 11;106(11):1753-62
references.pmid: 20378860
references.citation: Stem Cells. 2009 Jun;27(6):1421-32
references.pmid: 19489103
references.citation: Cell Transplant. 2009;18(7):801-14
references.pmid: 19796495
references.citation: Eur Heart J. 2006 May;27(9):1114-22
references.pmid: 16510464
references.citation: J Clin Invest. 2005 Mar;115(3):572-83
references.pmid: 15765139
references.citation: Blood. 2005 Apr 1;105(7):2821-7
references.pmid: 15591115
references.citation: Science. 1984 Jun 29;224(4656):1403-6
references.pmid: 6610211
references.citation: Trends Cell Biol. 2008 Apr;18(4):157-64
references.pmid: 18314333
references.citation: Stem Cell Rev. 2007 Dec;3(4):239-48
references.pmid: 18074246
references.citation: Cytotherapy. 2010 Apr;12(2):265-8
references.pmid: 19961282
references.citation: Transplantation. 2009 Mar 15;87(5):642-52
references.pmid: 19295307
references.citation: Circ Res. 2008 Nov 21;103(11):1204-19
references.pmid: 19028920
references.citation: Exp Neurol. 2002 Mar;174(1):11-20
references.pmid: 11869029
references.citation: Stem Cells. 2010 Mar 31;28(3):585-96
references.pmid: 19967788
references.citation: Tissue Eng Part A. 2008 Oct;14(10):1709-20
references.pmid: 18620480
references.citation: Nat Rev Endocrinol. 2010 Mar;6(3):139-48
references.pmid: 20173775
references.citation: Eur J Cardiothorac Surg. 2008 Oct;34(4):850-6
references.pmid: 18640847
references.citation: Cytotherapy. 2009;11(4):377-91
references.pmid: 19568970
references.citation: Lancet. 2008 May 10;371(9624):1553-4
references.pmid: 18468526
references.citation: Nat Med. 2003 Sep;9(9):1195-201
references.pmid: 12910262
references.citation: Exp Cell Res. 2009 Dec 10;315(20):3521-31
references.pmid: 19800880
references.citation: Mol Ther. 2008 Apr;16(4):749-56
references.pmid: 18362930
references.citation: J Biomech. 2010 Mar 22;43(5):807-17
references.pmid: 19962149
references.citation: Stem Cells. 2007 Aug;25(8):2118-27
references.pmid: 17478584
references.citation: J Cell Biochem. 2007 May 1;101(1):135-46
references.pmid: 17295203
references.citation: Biotechnol Bioeng. 2007 Feb 15;96(3):584-95
references.pmid: 16948169
references.citation: Am J Physiol Renal Physiol. 2008 Aug;295(2):F488-96
references.pmid: 18524862
references.citation: Cancer Res. 1999 Apr 1;59(7 Suppl):1693s-1700s
references.pmid: 10197582
references.citation: Cardiovasc Res. 2008 Feb 1;77(3):525-33
references.pmid: 18032392
references.citation: Blood. 2007 Nov 15;110(10):3691-4
references.pmid: 17684157
references.citation: Differentiation. 2004 Sep;72(7):319-26
references.pmid: 15554943
references.citation: Apoptosis. 2010 Apr;15(4):463-73
references.pmid: 19997978
references.citation: J Clin Invest. 2004 Jun;113(12):1701-10
references.pmid: 15199405
references.citation: J Am Coll Cardiol. 2008 Sep 16;52(12):971-8
references.pmid: 18786476
references.citation: Eur J Cardiothorac Surg. 2009 Oct;36(4):644-50
references.pmid: 19524448
references.citation: Circulation. 2004 Mar 30;109(12):1543-9
references.pmid: 15023891
references.citation: N Engl J Med. 2007 Sep 13;357(11):1121-35
references.pmid: 17855673
references.citation: J Thorac Cardiovasc Surg. 2008 Apr;135(4):799-808
references.pmid: 18374759
references.citation: Circulation. 2007 Aug 14;116(7):706-13
references.pmid: 17646577
references.citation: Circulation. 1995 Nov 1;92(9 Suppl):II365-71
references.pmid: 7586439
references.citation: Gene Ther. 2010 Jan;17(1):105-16
references.pmid: 19741731
references.citation: Stem Cells. 2009 Dec;27(12):3021-31
references.pmid: 19816949
references.citation: Circ Res. 2004 Apr 16;94(7):952-9
references.pmid: 14988226
references.citation: J Am Coll Cardiol. 2005 Oct 4;46(7):1339-50
references.pmid: 16198853
references.citation: Circulation. 2005 Aug 30;112(9 Suppl):I150-6
references.pmid: 16159808
references.citation: Mayo Clin Proc. 2009 Oct;84(10):893-902
references.pmid: 19797778
references.citation: Biochem Biophys Res Commun. 2007 Jun 8;357(3):779-84
references.pmid: 17445769
references.citation: Nat Biotechnol. 2002 Jun;20(6):587-91
references.pmid: 12042862
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18366-71
references.pmid: 19017790
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17499-504
references.pmid: 19805173
references.citation: Eur J Echocardiogr. 2010 Mar;11(2):165-71
references.pmid: 19946118
references.citation: J Cereb Blood Flow Metab. 2008 Feb;28(2):329-40
references.pmid: 17637706
references.citation: Immunity. 1995 Dec;3(6):673-82
references.pmid: 8777713
references.citation: Stem Cells. 2006 Apr;24(4):1030-41
references.pmid: 16253981
references.citation: Nat Neurosci. 1998 Aug;1(4):290-5
references.pmid: 10195162
references.citation: Circulation. 2002 Oct 8;106(15):1913-8
references.pmid: 12370212
references.citation: Gene Ther. 2008 Nov;15(21):1446-53
references.pmid: 18596829
references.citation: FASEB J. 2007 Nov;21(13):3763-70
references.pmid: 17586727
references.citation: Cell Transplant. 1997 Mar-Apr;6(2):125-34
references.pmid: 9142444
references.citation: Circ Res. 2004 Mar 19;94(5):678-85
references.pmid: 14739163
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):229-30
references.pmid: 18786406
references.citation: Circ Res. 2006 Sep 29;99(7):776-84
references.pmid: 16960098
references.citation: Scand Cardiovasc J. 2008 Feb;42(1):56-62
references.pmid: 17852784
references.citation: Acta Pharmacol Sin. 2008 Mar;29(3):333-40
references.pmid: 18298898
references.citation: J Orthop Res. 2009 Oct;27(10):1392-8
references.pmid: 19350658
references.citation: Ann N Y Acad Sci. 2007 Nov;1117:310-27
references.pmid: 18056051
references.citation: Mol Cancer Ther. 2006 Mar;5(3):755-66
references.pmid: 16546991
references.citation: Int J Oral Maxillofac Surg. 2006 Dec;35(12):1133-9
references.pmid: 17023144
references.citation: Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1320-9
references.pmid: 20154257
references.citation: Nature. 2004 Apr 8;428(6983):664-8
references.pmid: 15034593