title: Targeting improves MSC treatment of inflammatory bowel disease.
abstract: 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.
authors.affiliation: Department of Orthopedics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: In Kap
authors.initials: IK
authors.lastname: Ko
authors.forename: Byung-Gyu
authors.initials: BG
authors.lastname: Kim
authors.forename: Amad
authors.initials: A
authors.lastname: Awadallah
authors.forename: Jenifer
authors.initials: J
authors.lastname: Mikulan
authors.forename: Paul
authors.initials: P
authors.lastname: Lin
authors.forename: John J
authors.initials: JJ
authors.lastname: Letterio
authors.forename: James E
authors.initials: JE
authors.lastname: Dennis
mesh_terms: 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
chemical_list: D000906:Antibodies; D019010:Vascular Cell Adhesion Molecule-1
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