Xenogeneic cardiac extracellular matrix scaffolds with or without seeded mesenchymal stem cells exhibit distinct in vivo immunosuppressive and regenerative properties.

Abstract

We demonstrated that an antigen-removal (AR) approach utilizing principles of differential solubility for production of a xenogeneic rat cardiac extracellular matrix scaffold results in improved recellularization efficiency with human and mouse mesenchymal stem cells (MSCs) in vitro. Furthermore, we tested the immune response to AR scaffolds versus allograft and xenograft controls with or without MSC recellularization using a rat to mouse subcutaneous model. We showed that AR scaffolds and allograft controls resulted in significant adipose tissue transformation after 12weeks. Paradoxically, MSCs had a positive impact in the immune response to xenografts, but had the opposite effect in AR scaffolds, resulting in chronic inflammatory response, which might be attributed to a change of their phenotype following recellularization into scaffolds.