Human amniotic epithelial cells induce localized cell-mediated immune privilege in vitro: implications for pancreatic islet transplantation

摘要: Chronic systemic immunosuppression in cell replacement therapy restricts its clinical application. This study sought to explore the potential of cell-based immune modulation as an alternative immunosuppressive drug context pancreatic islet transplantation. Human amniotic epithelial cells (AEC) possess innate anti-inflammatory and properties that were utilized create localized privilege vitro culture system. Cellular constructs composed human islets AEC (islet/AEC) bioengineered under defined rotational conditions. Insulin secretory capacity was validated by glucose challenge immunomodulatory characterized using a peripheral blood lymphocyte (PBL) proliferation assay. Results compared control or cultured alone. Studies employing AEC-conditioned medium examined role soluble factors, fluorescence immunocytochemistry used identify putative mediators response isolated monocultures. Sustained, physiologically appropriate insulin secretion observed both islet/AEC constructs. Activation resting PBL occurred on exposure alone but this significantly (p <0.05) attenuated presence medium. Mitogen (phytohaemagglutinin, 5 µg/ml)-induced sustained contact with abrogated AEC, conditioned medium, Immunocytochemical analysis monocultures identified subpopulation expressed proapoptosis protein Fas ligand. demonstrates exhibit no impairment s-cell function. The data suggest transplanted may benefit from status conferred them consequence their close proximity AEC. Such approach reduce need for chronic immunosuppression, thus making transplantation more attractive treatment option management insulin-dependent diabetes.