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Hypoxia is a main cause of considerable islet loss during first days after intraportal transplantation. The aim of this study was to investigate whether shielding of human islets (HI) with human amniotic epithelial cells (hAECs), which are known to possess immunomodulatory, anti-inflammatory and regenerative properties could improve islet engraftment and survival.Shielded islets were generated on microwells by mixing HI and hAECs at ratio of 1:800 (800 hAECs per HI). Next, 1200 shielded or neat islets, were transplanted under the kidney capsule of diabetic SCID mice. The ability of hAECs to adhere to human islets was analyzed by confocal microscopy. Islet function was assessed by dynamic insulin release in response to glucose in vitro. Blood glucose and weight were monitored regularly. Intravenous glucose tolerance test was performed 1 month after transplantation. Graft morphology and vascularisation were evaluated by immunohistochemistry.HI shielded with hAECs had greater cellular insulin content and increased glucose-stimulated insulin secretion. Transplantation of shielded islets resulted in considerably earlier normoglycemia and vascularization, improved glucose tolerance, and increased insulin content.Co-transplantation of islets with hAECs had a profound impact on the remodelling process, maintaining islet organisation and improving islet revascularisation. Moreover, hAECs improved the capacity of islets to reverse hyperglycaemia.