title: Mesenchymal stem cells as a vector for the inflammatory prostate microenvironment.
abstract: Mesenchymal stem cells (MSCs) have an inherent tropism for sites of inflammation, which are frequently present in sites of cancer, including prostatic lesions. MSCs have been defined as CD73/CD90/CD105 triple-positive cells in the absence of hematopoietic lineage markers with the ability to differentiate into multiple mesodermal lineages, including osteoblasts, adipocytes, and chondrocytes. Our group has previously demonstrated that MSCs represent between 0.01 and 1.1% of the total cells present in human prostatectomy tissue. In addition to their multi-lineage differentiation potential, MSCs are immunoprivileged in nature and have a range of immunomodulatory effects on both the innate and adaptive arms of the immune system. MSCs have been detected in an increasing array of tissues, and evidence suggests that they are likely present in perivascular niches throughout the body. These observations suggest that MSCs represent critical mediators of the overall immune response during physiological homeostasis and likely contribute to pathophysiological conditions as well. Chronic inflammation has been suggested as an initiating event and progression factor in prostate carcinogenesis, a process in which the immunosuppressive properties of MSCs may play a role. MSCs have also been shown to influence malignant progression through a variety of other mechanisms, including effects on tumor proliferation, angiogenesis, survival, and metastasis. Additionally, human bone marrow-derived MSCs have been shown to traffic to human prostate cancer xenografts in immunocompromised murine hosts. The trafficking properties and immunoprivileged status of MSCs suggest that they can be exploited as an allogeneic cell-based vector to deliver cytotoxic or diagnostic agents for therapy.
authors: Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21287, USA.
authors: W Nathaniel
authors: WN
authors: Brennen
authors: Samuel R
authors: SR
authors: Denmeade
authors: John T
authors: JT
authors: Isaacs
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011467:Prostate / Q000473:pathology*
keywords: MSC; inflammation; mesenchymal stem cell; multipotent stromal cell; prostate cancer
references: Breast Cancer Res Treat. 2007 Oct;105(2):157-67
references: 17221158
references: Stem Cells. 2012 Jul;30(7):1575-8
references: 22553154
references: Cell Stem Cell. 2008 Feb 7;2(2):141-50
references: 18371435
references: Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2199-204
references: 11854516
references: Cytotherapy. 2010 Sep;12(5):615-25
references: 20230221
references: Mol Cancer Ther. 2012 Feb;11(2):257-66
references: 22323494
references: Gene Ther. 2008 May;15(10):730-8
references: 18401438
references: Blood. 2011 May 5;117(18):4826-35
references: 21389316
references: Cancer. 2009 Jan 1;115(1):13-22
references: 19051291
references: J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86
references: 19958962
references: Blood. 2012 Oct 25;120(17):3436-43
references: 22966167
references: Bone Marrow Transplant. 2013 Apr;48(4):544-50
references: 23064040
references: Front Med. 2011 Mar;5(1):94-100
references: 21681681
references: Nat Rev Cancer. 2007 Apr;7(4):256-69
references: 17384581
references: Cancer Metastasis Rev. 1991 Oct;10(3):263-74
references: 1722435
references: Muscle Nerve. 1995 Dec;18(12):1417-26
references: 7477065
references: Stem Cells. 2008 Jan;26(1):279-89
references: 17962701
references: J Exp Med. 2006 May 15;203(5):1235-47
references: 16636132
references: Eur J Cancer. 2012 Jan;48(1):129-37
references: 21664124
references: Cancer Control. 2006 Jul;13(3):158-68
references: 16885911
references: J Neurosci Res. 2000 Aug 15;61(4):364-70
references: 10931522
references: Cancer Metastasis Rev. 2010 Jun;29(2):249-61
references: 20411303
references: Cell. 2011 Mar 4;144(5):646-74
references: 21376230
references: Clin Pharmacol Ther. 2007 Sep;82(3):241-3
references: 17700588
references: Blood. 2006 Jun 15;107(12):4817-24
references: 16493000
references: Stem Cells Dev. 2005 Jun;14(3):252-65
references: 15969620
references: Stem Cells. 2011 Jan;29(1):11-9
references: 21280155
references: Gene Ther. 2004 Jul;11(14):1155-64
references: 15141157
references: Nat Med. 2012 Sep;18(9):1359-68
references: 22863786
references: Exp Cell Res. 2010 May 15;316(9):1648-50
references: 20171963
references: Bone. 2007 Feb;40(2):382-90
references: 17049329
references: Cytotherapy. 2005;7(5):393-5
references: 16236628
references: PLoS One. 2012;7(2):e30563
references: 22363446
references: Exp Hematol. 1976 Sep;4(5):267-74
references: 976387
references: Exp Mol Pathol. 2003 Dec;75(3):248-55
references: 14611816
references: Cancer Gene Ther. 2010 Apr;17(4):289-97
references: 19876078
references: Cytokine Growth Factor Rev. 2010 Apr-Jun;21(2-3):119-26
references: 20226717
references: Cancer Gene Ther. 2007 Nov;14(11):894-903
references: 17693990
references: PLoS One. 2012;7(9):e45052
references: 23028757
references: Blood. 2003 May 1;101(9):3722-9
references: 12506037
references: Clin Exp Allergy. 2011 Apr;41(4):526-34
references: 21255158
references: Arch Pharm Res. 2011 Apr;34(4):599-606
references: 21544725
references: Biochem Biophys Res Commun. 2009 Feb 20;379(4):1114-9
references: 19161980
references: Ann Surg. 2011 Nov;254(5):767-74; discussion 774-5
references: 22042469
references: Inflamm Allergy Drug Targets. 2009 Jun;8(2):110-23
references: 19530993
references: Semin Cell Dev Biol. 2010 Feb;21(1):19-25
references: 19857592
references: Chest. 2013 Jun;143(6):1590-1598
references: 23172272
references: PLoS One. 2010 Sep 23;5(9):e12920
references: 20886110
references: J Neuroimmunol. 2010 Jan 25;218(1-2):140-4
references: 19914721
references: Proteomics. 2007 Aug;7(16):2881-94
references: 17654458
references: J Orthop Res. 2005 Nov;23(6):1383-9
references: 15936917
references: J Cell Biochem. 2011 Nov;112(11):3234-45
references: 22009438
references: Biol Blood Marrow Transplant. 2005 May;11(5):389-98
references: 15846293
references: Immunol Cell Biol. 2007 Feb-Mar;85(2):85-92
references: 17213831
references: Nat Rev Cancer. 2006 May;6(5):392-401
references: 16572188
references: Blood. 2006 Sep 15;108(6):2114-20
references: 16690970
references: Cytotherapy. 2010;12(1):17-30
references: 19878082
references: Stem Cells Dev. 2010 Apr;19(4):481-90
references: 19788395
references: Circulation. 2010 Dec 7;122(23):2419-29
references: 21098445
references: J Cell Biochem. 2011 Aug;112(8):1963-8
references: 21445861
references: J Natl Cancer Inst. 2004 Nov 3;96(21):1593-603
references: 15523088
references: Mod Pathol. 2010 Oct;23(10):1346-56
references: 20562849
references: Cancer Res. 2010 Sep 1;70(17):6945-56
references: 20699369
references: Prostate. 2010 Apr 1;70(5):473-81
references: 19902472
references: PLoS One. 2011;6(12):e28321
references: 22205945
references: Int J Cancer. 2003 Oct 20;107(1):1-10
references: 12925950
references: Bull Exp Biol Med. 2006 Jan;141(1):147-51
references: 16929987
references: Exp Cell Res. 2005 Apr 15;305(1):33-41
references: 15777785
references: Hum Gene Ther. 2011 Apr;22(4):439-49
references: 20925460
references: Clin Cancer Res. 2009 Dec 1;15(23):7246-55
references: 19934299
references: Cancer Res. 2008 Jun 1;68(11):4331-9
references: 18519693
references: Ann Rheum Dis. 2009 Aug;68(8):1352-9
references: 18647856
references: Expert Opin Biol Ther. 2010 Oct;10(10):1453-68
references: 20831449
references: Prostate. 2009 Jun 15;69(9):991-1000
references: 19267366
references: J Cell Physiol. 2011 Mar;226(3):843-51
references: 20857424
references: N Engl J Med. 2005 May 5;352(18):1839-42
references: 15872196
references: Cancer Res. 2010 May 1;70(9):3718-29
references: 20388793
references: Stem Cells. 2010 Dec;28(12):2229-38
references: 20945332
references: Histopathology. 2012 Jan;60(1):199-215
references: 22212087
references: J Cell Biochem. 2013 May;114(5):1135-44
references: 23192362
references: Cardiovasc Res. 1996 Oct;32(4):687-98
references: 8915187
references: Mol Ther. 2010 Jan;18(1):223-31
references: 19844197
references: Blood. 2006 Feb 15;107(4):1484-90
references: 16239427
references: Cell Stem Cell. 2010 Dec 3;7(6):718-29
references: 21112566
references: Cytotherapy. 2008;10(8):784-95
references: 18951271
references: Cancer Res. 1999 Oct 1;59(19):5002-11
references: 10519415
references: Lancet. 2004 May 1;363(9419):1439-41
references: 15121408
references: Biochem Biophys Res Commun. 2007 Mar 16;354(3):700-6
references: 17257581
references: Cancer Gene Ther. 2013 May;20(5):308-16
references: 23618949
references: J Cell Mol Med. 2011 Feb;15(2):433-44
references: 19799647
references: Mol Ther. 2011 Sep;19(9):1704-13
references: 21587211
references: Tissue Eng. 2007 Apr;13(4):659-66
references: 17371203
references: Prostate. 2010 Jul 1;70(10):1066-73
references: 20232361
references: Basic Res Cardiol. 2005 Nov;100(6):471-81
references: 16237508
references: Cell Cycle. 2006 Aug;5(15):1597-601
references: 16880743
references: J Gene Med. 2008 Oct;10(10):1071-82
references: 18671316
references: J Orthop Res. 1991 Sep;9(5):641-50
references: 1870029
references: Lancet. 2008 May 10;371(9624):1579-86
references: 18468541
references: Nat Rev Mol Cell Biol. 2011 Feb;12(2):126-31
references: 21253000
references: Cell. 2007 Jun 29;129(7):1377-88
references: 17604725
references: Vasc Cell. 2011 Feb 08;3(1):5
references: 21349162
references: Nature. 2007 Oct 4;449(7162):557-63
references: 17914389
references: Cell Res. 2008 Apr;18(4):500-7
references: 18364678
references: Stem Cells. 2007 Dec;25(12):3215-22
references: 17901402
references: Cancer Res. 2002 Jul 1;62(13):3603-8
references: 12097260
references: Exp Dermatol. 2006 Nov;15(11):865-74
references: 17002683
references: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3806-11
references: 19234121
references: Arthritis Rheum. 2005 Aug;52(8):2521-9
references: 16052568
references: Cytokine. 2010 Jun;50(3):317-21
references: 20185331
references: Stem Cell Rev Rep. 2011 Mar;7(1):64-76
references: 20396979
references: Cytotherapy. 2006;8(4):315-7
references: 16923606
references: Stem Cells. 2007 Nov;25(11):2896-902
references: 17901396
references: Histol Histopathol. 2011 Jul;26(7):941-51
references: 21630223
references: Cell Stem Cell. 2008 Sep 11;3(3):301-13
references: 18786417
references: Blood. 2007 Feb 15;109(4):1422-32
references: 17038530
references: Stem Cells Dev. 2012 Sep 20;21(14):2724-52
references: 22468918
references: Eur J Immunol. 2005 May;35(5):1482-90
references: 15827960
references: Oncogene. 2010 Jun 3;29(22):3185-95
references: 20305695
references: J Natl Cancer Inst. 2003 Jul 2;95(13):990-1000
references: 12837835
references: Mol Biol Cell. 2002 Dec;13(12):4279-95
references: 12475952
references: Eur Urol. 2008 Dec;54(6):1379-84
references: 18036719
references: Science. 2004 Feb 6;303(5659):848-51
references: 14764882
references: Cytotherapy. 2008;10(4):320-30
references: 18574765
references: Blood. 2006 Jan 1;107(1):367-72
references: 16141348
references: Cancer Res. 2009 Feb 15;69(4):1255-8
references: 19208837
references: BJU Int. 2012 Apr;109 Suppl 3:22-6
references: 22458488
references: J Int Med Res. 2012;40(1):317-27
references: 22429371
references: Science. 1999 Apr 2;284(5411):143-7
references: 10102814
references: Stem Cells. 2008 Nov;26(11):2981-90
references: 18757301
references: Stem Cells. 2013 Oct;31(10):2042-6
references: 23681848
references: Cell Stem Cell. 2009 Jul 2;5(1):54-63
references: 19570514
references: Cancer Lett. 2010 Apr 28;290(2):157-66
references: 19786319
references: Cytotherapy. 2009;11(8):1020-31
references: 19929466
references: Cancer Invest. 2012 Aug;30(7):513-8
references: 22646310
references: Mol Ther. 2012 Jan;20(1):14-20
references: 22008910
references: Stem Cells. 2007 Aug;25(8):2025-32
references: 17510220
references: Cells Tissues Organs. 2003;174(3):101-9
references: 12835573
references: Science. 2010 Aug 27;329(5995):1004
references: 20798289
references: Cancer Res. 2007 Jul 1;67(13):6304-13
references: 17616689
references: N Engl J Med. 2003 Jul 24;349(4):366-81
references: 12878745
references: Mol Ther. 2011 Jun;19(6):1161-9
references: 21386822
references: Cells Tissues Organs. 2001;169(1):12-20
references: 11340257
references: Prostate. 2010 Nov 1;70(15):1709-15
references: 20564322
references: J Cell Mol Med. 2011 Mar;15(3):635-46
references: 20184663
references: Blood. 2011 Dec 15;118(25):e184-91
references: 22034631
references: Stem Cells Transl Med. 2012 Dec;1(12):886-97
references: 23283550
references: Am J Pathol. 2004 Nov;165(5):1543-56
references: 15509525
references: Blood. 2005 Feb 15;105(4):1815-22
references: 15494428
references: JAMA. 2012 Dec 12;308(22):2369-79
references: 23117550
references: Adv Drug Deliv Rev. 2012 Jun 1;64(8):739-48
references: 21740940
references: Stem Cells Dev. 2010 Nov;19(11):1803-9
references: 20163251
references: Nat Med. 2011 Mar;17(3):320-9
references: 21383745
references: Bone Marrow Transplant. 2006 May;37(10):967-76
references: 16670702
references: Stem Cells Dev. 2012 May 1;21(7):1112-23
references: 21671747
references: Exp Hematol. 2005 Nov;33(11):1402-16
references: 16263424
references: J Clin Invest. 2010 Sep;120(9):3340-9
references: 20679726
references: Cancer Res. 2010 Aug 1;70(15):6393-6
references: 20631079
references: Cell Tissue Kinet. 1970 Oct;3(4):393-403
references: 5523063
references: J Cell Biochem. 2003 Jun 1;89(3):462-73
references: 12761880
references: Blood. 2005 Dec 15;106(13):4057-65
references: 16118325
references: J Immunol. 2006 Mar 1;176(5):2864-71
references: 16493043
references: Tissue Eng. 2006 Oct;12(10):2813-23
references: 17518650
references: J Natl Cancer Inst. 2011 Nov 16;103(22):1665-75
references: 21917607
references: Transplantation. 2004 Aug 27;78(4):503-8
references: 15446307
references: Prostate. 2007 Sep 1;67(12):1265-76
references: 17597114
references: Cell Stem Cell. 2008 Apr 10;2(4):313-9
references: 18397751
references: Cytotherapy. 2011 Mar;13(3):310-7
references: 20795757
references: Oncotarget. 2013 Jan;4(1):106-17
references: 23362217
references: Stem Cells. 2006 Feb;24(2):386-98
references: 16123384
references: Trends Mol Med. 2010 May;16(5):203-9
references: 20335067
references: Prostate. 2013 May;73(6):651-6
references: 23129407
references: Exp Cell Res. 2009 Oct 15;315(17):3004-13
references: 19447103
references: Haematologica. 2007 Sep;92(9):1208-15
references: 17666368
references: Transplantation. 2003 Feb 15;75(3):389-97
references: 12589164
references: Exp Hematol. 2003 Oct;31(10):890-6
references: 14550804
references: Immunol Lett. 2007 Jun 15;110(2):91-100
references: 17507101
references: Drug Resist Updat. 2012 Feb-Apr;15(1-2):39-49
references: 22335920
references: Blood. 2006 Mar 15;107(6):2570-7
references: 16293599
references: Nat Commun. 2013;4:1795
references: 23653207
references: Blood. 2003 Apr 15;101(8):2999-3001
references: 12480709
references: Exp Cell Res. 2008 Apr 15;314(7):1575-84
references: 18325494
references: Eur Urol. 2011 Jul;60(1):106-17
references: 21497433
references: J Cell Sci. 2005 Sep 1;118(Pt 17):3925-36
references: 16091422
references: Cell Transplant. 2009;18(12):1369-79
references: 19849895
references: J Clin Invest. 2007 Apr;117(4):989-96
references: 17347686
references: Am J Pathol. 1999 Dec;155(6):1985-92
references: 10595928
references: J Urol. 1984 Sep;132(3):474-9
references: 6206240
references: J Natl Cancer Inst. 2007 Mar 7;99(5):376-85
references: 17341729
references: J Pathol. 2009 Jan;217(2):318-24
references: 19023885
references: J Cell Sci. 2006 Jun 1;119(Pt 11):2204-13
references: 16684817
references: Eur Urol. 2007 May;51(5):1202-16
references: 17182170
references: Prostate. 2006 Feb 1;66(2):124-34
references: 16161154
references: Clin Cancer Res. 2009 Dec 1;15(23):7175-85
references: 19920103
references: Gene Ther. 2008 Nov;15(21):1446-53
references: 18596829
references: Blood. 2005 Mar 1;105(5):2214-9
references: 15514012
references: Stem Cells Dev. 2011 Jan;20(1):1-10
references: 20670160
references: Int J Biochem Cell Biol. 2013 Aug;45(8):1869-77
references: 23735324
references: Stem Cell Rev Rep. 2011 Sep;7(3):560-8
references: 21437576
references: Stem Cells. 2004;22(7):1263-78
references: 15579645
references: PLoS One. 2012;7(10):e47559
references: 23133515
references: J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2:112-20
references: 22320928
references: Mol Cancer Res. 2012 Apr;10(4):494-503
references: 22290877
references: Mol Cancer Ther. 2006 Mar;5(3):755-66
references: 16546991
references: Ann Surg. 2009 Nov;250(5):747-53
references: 19826249
references: Semin Cell Dev Biol. 2010 Feb;21(1):33-9
references: 19896548
references: Biol Blood Marrow Transplant. 2011 Apr;17(4):534-41
references: 20457269
references: Scand J Immunol. 2003 Jan;57(1):11-20
references: 12542793