Dataset Information

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.

SUBMITTER: Chang CW

PROVIDER: S-EPMC4829265 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Chang Chia Wei CW Petrie Tye T Clark Alycia A Lin Xin X Sondergaard Claus S CS Griffiths Leigh G LG

PloS one 20160412 4

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 cardio ...[more]

PMID: 27070546

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Project description:Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be of biological or synthetic nature. In the current clinical scenario, amongst biological patches, are gaining very much interest those derived from decellularization of xenogeneic scaffold. These patches maintain their natural architecture of the extracellular matrix (ECM) after the removal of their native cells. Moreover, once implanted in the host, they promote tissue regeneration and repair, encourage angiogenesis, migration, proliferation, and host’s cell differentiation mechanisms. Finally, in the host, decellularized xenogeneic patches, after cells repopulation, reduce immuno-mediated response against the graft thus preventing device failure. Small intestinal submucosa (SIS) from porcine showed such properties in alternative clinical scenarios. The US FDA approved its use in humans for urogenital procedures, such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie’s disease, penile chordee, and urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for the skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are still controversial. In this study, we aimed to validate our decellularization protocols for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100) which is not more available on the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, mechanics, biocompatibility and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, smooth or wrinkle, which are equivalent for ultrastructure and biochemical profile. Furthermore, Tergitol 15 S 9 treatment do not modify the mechanics of the tissue, resulting comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, our study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performance compared to Triton X 100 in all the fields of characterization explored and for all the components of the SIS: wrinkled and smooth.

Project description:The increasing economic burden of wound healing in healthcare systems requires the development of functional therapies. Xenografts with preserved extracellular matrix (ECM) structure and biofunctional components overcome major limitations of autografts and allografts (e.g. availability) and artificial biomaterials (e.g. foreign body response). Although porcine mesothelium is extensively used in clinical practice, it is under-investigated for wound healing applications. Herein, we compared the biochemical and biological properties of the only two commercially available porcine mesothelium grafts (Meso Biomatrix® and Puracol® Ultra ECM) to traditionally used wound healing grafts (Endoform™, ovine forestomach and MatriStem®, porcine urinary bladder) and biomaterials (Promogran™, collagen/oxidized regenerated cellulose). The Endoform™ and the Puracol® Ultra ECM showed the highest (p<0.05) soluble collagen and elastin content. The MatriStem® had the highest (p<0.05) basic fibroblast growth factor (FGFb) content, whereas the Meso Biomatrix® had the highest (p<0.05) transforming growth factor beta-1 (TGF-β1) and vascular endothelial growth factor (VEGF) content. All materials showed tissue-specific structure and composition. The Endoform™ and the Meso Biomatrix® had some nuclei residual matter. All tissue grafts showed similar (p>0.05) response to enzymatic degradation, whereas the Promogran™ was not completely degraded by matrix metalloproteinase (MMP)-8 and was completely degraded by elastase. The Promogran™ showed the highest (p<0.05) permeability to bacterial infiltration. The Promogran™ showed by far the lowest dermal fibroblast and THP-1 attachment and growth. All tested materials showed significantly lower (p<0.05) tumor necrosis factor-alpha (TNF-α) expression than the lipopolysaccharides group. The MatriStem® and the Puracol® Ultra ECM promoted the highest (p<0.05) number of micro-vessel formation, whereas the Promogran™ the lowest (p<0.05). Collectively, these data confer that porcine mesothelium has the potential to be used as a wound healing material, considering its composition, resistance to enzymatic degradation, cytocompatibility, and angiogenic potential.

Dataset Information

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

Publications

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

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