Targeting improves MSC treatment of inflammatory bowel disease.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs) have the potential to rescue IBD owing to their immunosuppressive capabilities and clinical studies have shown positive influence on intestinal graft versus host disease. We demonstrate here a new method to coat MSCs with antibodies against addressins to enhance their delivery to the colon and thereby increase the therapeutic effectiveness. Bioluminescence imaging (BLI) demonstrated that vascular cell adhesion molecule antibody (Ab)-coated MSCs (Ab(VCAM-1)- MSCs) had the highest delivery efficiency to inflamed mesenteric lymph node (MLN) and colon compared to untreated MSCs, Ab(isotype)-MSCs, and Ab(MAdCAM)-MSCs. Therapeutically, when mice with IBD were injected with addressin Ab-coated MSCs, they showed dramatically improved survival rates, higher IBD therapeutic scores, and significantly improved body weight gain compared to mice injected with MSCs only, isotype Ab, free Ab plus MSCs, or vehicle-only controls. These data demonstrate that anti-addressin Ab coating on MSC increased cell delivery to inflamed colon and increased the efficacy of MSC treatment of IBD. This is the first study showing an increased therapeutic efficacy when stem cells are first coated with antibodies specifically target them to inflamed sites.
Ko
In Kap
IK
Department of Orthopedics, Case Western Reserve University, Cleveland, Ohio, USA.
Kim
Byung-Gyu
BG
Awadallah
Amad
A
Mikulan
Jenifer
J
Lin
Paul
P
Letterio
John J
JJ
Dennis
James E
JE
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008163:Luminescent Measurements; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000737:chemistry* / Q000166:cytology* / Q000502:physiology; D051379:Mice; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D000906:Antibodies; D019010:Vascular Cell Adhesion Molecule-1
Cell Stem Cell. 2008 Feb 7;2(2):141-50
18371435
Stem Cells. 2008 Jan;26(1):244-53
17932424
Blood. 2002 May 15;99(10):3838-43
11986244
Bioconjug Chem. 2008 Nov 19;19(11):2105-9
18973352
Ann Rheum Dis. 2010 Jan;69(1):241-8
19124525
Lancet. 2008 May 10;371(9624):1579-86
18468541
Cell Res. 2007 Mar;17(3):240-8
17325691
Blood. 2005 Feb 15;105(4):1815-22
15494428
J Immunol. 1995 Aug 1;155(3):1151-64
7636184
Gastroenterology. 2006 May;130(6):1707-20
16697735
Gut. 2009 Jul;58(7):929-39
19136511
Diabetes. 2008 Jul;57(7):1759-67
18586907
J Intern Med. 2007 Nov;262(5):509-25
17949362
Clin Immunol. 2008 Jun;127(3):348-58
18387852
J Orthop Res. 2004 Jul;22(4):735-41
15183428
Inflamm Allergy Drug Targets. 2009 Jun;8(2):110-23
19530993
Blood. 2005 Sep 1;106(5):1755-61
15905186
J Immunol. 1997 Mar 1;158(5):2099-106
9036954
Int J Colorectal Dis. 2006 Jan;21(1):71-8
15856265
J Pharmacol Exp Ther. 2000 Oct;295(1):183-9
10991977
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5096-100
1711218
Int J Colorectal Dis. 2003 Sep;18(5):451-4
12756590
Circulation. 2003 Aug 19;108(7):863-8
12900340
Nat Immunol. 2007 Feb;8(2):191-7
17136045
Arthritis Rheum. 2008 May;58(5):1377-88
18438858
Cell Stem Cell. 2009 Jul 2;5(1):54-63
19570514
Exp Hematol. 2008 Mar;36(3):309-18
18279718
Eur J Immunol. 2009 Aug;39(8):2026-30
19672897
J Nucl Med. 2007 Dec;48(12):2011-20
18006616
Annu Rev Immunol. 2002;20:495-549
11861611
J Pharmacol Exp Ther. 2008 Aug;326(2):523-31
18448866
Nat Med. 2008 Feb;14(2):181-7
18193058
Cell Stem Cell. 2009 Mar 6;4(3):206-16
19265660
Haematologica. 2007 Jul;92(7):881-8
17606437
Mol Imaging. 2004 Jan;3(1):9-23
15142408
Biomaterials. 2009 Aug;30(22):3702-10
19375791
Blood. 2004 Nov 15;104(10):3091-6
15280192
Leukemia. 2005 Sep;19(9):1597-604
16049516
Ann Neurol. 2007 Mar;61(3):219-27
17387730
Gastroenterology. 1998 Jul;115(1):182-205
9649475
J Bone Miner Res. 1999 May;14(5):700-9
10320518
J Pathol. 2009 Jul;218(3):350-9
19291714