Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

• DOI: 10.1073/pnas.1213228110
• Publication Date: 2013-08-13T01:53:00Z
• Authors: Jonathan M. Fishman; Mark W. Lowdell; Luca Urbani; Tahera Ansari; Alan J. Burns; Mark Turmaine; Janet North; Paul Sibbons; Alexander M. Seif...; Kathryn J. Wood; Martin A. Birchall; Paolo De Coppi
• Keywords: Decellularization; Xenotransplantation; Proinflammatory cytokine

Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis an emerging generation tissue-engineered organ and tissue replacements capable transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility absence rejection. The humoral immune response to has been well documented, but there is a lack data on cell-mediated toward them in vitro vivo. Skeletal muscle were decellularized, characterized vitro, xenotransplanted. cellular was evaluated by immunohistochemistry quantified stereologically. T-cell proliferation cytokines, as assessed flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye cytometric bead array, formed surrogate marker correlate vivo host scaffold. free major histocompatibility complex class I II antigens found exert anti-inflammatory immunosuppressive effects, evidenced delayed biodegradation time vivo; reduced sensitized proliferative activity vitro; IL-2, IFN-γ, raised IL-10 levels cell-culture supernatants; polarization macrophage M2 phenotype; improved survival donor-derived xenogeneic cells at 2 4 wk polarize responses away from classical TH1-proinflammatory profile appear down-regulate xeno TH1 effector function inducing state peripheral hyporesponsiveness. These results have substantial implications future clinical application therapies.