title: Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications.
abstract: In this study, we investigate the translational potential of a novel combined construct using an FDA-approved decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) seeded with human or porcine mesenchymal stem cells (MSCs) for cardiovascular indications. With the emerging success of individual component in various clinical applications, the combination of SIS-ECM with MSCs could provide additional therapeutic potential compared to individual components alone for cardiovascular repair. We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes. Additionally, we evaluated the ability of porcine MSCs to modulate recipient graft-specific response towards SIS-ECM in a porcine cardiac patch in vivo model. Specifically, we determined: 1) in vitro loading-capacity of human MSCs on SIS-ECM, 2) effect of cell seeding on SIS-ECM structure, compositions and mechanical properties, 3) effect of SIS-ECM seeding on human MSC phenotypes and differentiation potential, and 4) optimal orientation and dose of porcine MSCs seeded SIS-ECM for an in vivo cardiac application. In this study, histological structure, biochemical compositions and mechanical properties of the FDA-approved SIS-ECM biomaterial were retained following MSCs repopulation in vitro. Similarly, the cellular phenotypes and differentiation potential of MSCs were preserved following seeding on SIS-ECM. In a porcine in vivo patch study, the presence of porcine MSCs on SIS-ECM significantly reduced adaptive T cell response regardless of cell dose and orientation compared to SIS-ECM alone. These findings substantiate the clinical translational potential of combined SIS-ECM seeded with MSCs as a promising therapeutic candidate for cardiac applications.
authors.affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Chia Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Surgery, School of Medicine, University of California, Davis, Sacramento, California, United States of America.
authors.forename: Tye
authors.initials: T
authors.lastname: Petrie
authors.affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Alycia
authors.initials: A
authors.lastname: Clark
authors.affiliation: Department of Surgery, School of Medicine, University of California, Davis, Sacramento, California, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Surgery, School of Medicine, University of California, Davis, Sacramento, California, United States of America.
authors.forename: Claus S
authors.initials: CS
authors.lastname: Sondergaard
authors.affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Leigh G
authors.initials: LG
authors.lastname: Griffiths
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology* / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D013552:Swine; D013601:T-Lymphocytes / Q000502:physiology; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials