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Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications.

Chang CW, Petrie T, Clark A, Lin X, Sondergaard CS, Griffiths LG - PLoS ONE (2016)

Bottom Line: We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes.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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.

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.

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Uniaxial Tensile Testing of SIS-ECM.(A) Data were plotted as mean ± SD for UTS (n = 8) and (B) Young’s modulus (n = 6). Mechanical properties of SIS-ECM were maintained before and after hMSC-seeding.
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pone.0153412.g004: Uniaxial Tensile Testing of SIS-ECM.(A) Data were plotted as mean ± SD for UTS (n = 8) and (B) Young’s modulus (n = 6). Mechanical properties of SIS-ECM were maintained before and after hMSC-seeding.

Mentions: Uniaxial tensile testing was performed to examine the mechanical integrity of SIS-ECM and effect of hMSC-seeding. All samples were observed to fail at the dogbone region. No statistical significance was detected for UTS and Young’s modulus between SIS-ECM group (8.90 ± 1.83 MPa and 14.04 ± 3.32 MPa), hMSC-seeded group (8.05 ± 1.34 MPa and 10.76 ± 4.52 MPa) or non-seeded group (9.78 ± 2.94 MPa and 13.47 ± 3.48 MPa) (p = 0.2953 for UTS and p = 0.3107 for Young’s modulus) (Fig 4A and 4B).


Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications.

Chang CW, Petrie T, Clark A, Lin X, Sondergaard CS, Griffiths LG - PLoS ONE (2016)

Uniaxial Tensile Testing of SIS-ECM.(A) Data were plotted as mean ± SD for UTS (n = 8) and (B) Young’s modulus (n = 6). Mechanical properties of SIS-ECM were maintained before and after hMSC-seeding.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829265&req=5

pone.0153412.g004: Uniaxial Tensile Testing of SIS-ECM.(A) Data were plotted as mean ± SD for UTS (n = 8) and (B) Young’s modulus (n = 6). Mechanical properties of SIS-ECM were maintained before and after hMSC-seeding.
Mentions: Uniaxial tensile testing was performed to examine the mechanical integrity of SIS-ECM and effect of hMSC-seeding. All samples were observed to fail at the dogbone region. No statistical significance was detected for UTS and Young’s modulus between SIS-ECM group (8.90 ± 1.83 MPa and 14.04 ± 3.32 MPa), hMSC-seeded group (8.05 ± 1.34 MPa and 10.76 ± 4.52 MPa) or non-seeded group (9.78 ± 2.94 MPa and 13.47 ± 3.48 MPa) (p = 0.2953 for UTS and p = 0.3107 for Young’s modulus) (Fig 4A and 4B).

Bottom Line: We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes.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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus