en
Scientific article
Open access
English

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Publication date2020
Abstract

Hypoxia is a major cause of considerable islet loss during the early post-transplantation period. Here, we investigate whether shielding islets with human amniotic epithelial cells (hAECs), which possess anti-inflammatory and regenerative properties, improves islet engraftment and survival. Shielded islets were generated on agarose microwells by mixing rat (RI) or human (HI) islets and hAECs (100 hAECs/IEQ). Islet secretory function and viability were assessed after culture in hypoxia (1% O2) or normoxia (21% O2) in vitro. In vivo function was evaluated after transplantation under the kidney capsule of diabetic immunodeficient mice. Graft morphology and vascularization were evaluated by immunohistochemistry. Both shielded RI and HI show higher viability and increased glucose-stimulated insulin secretion after exposure to hypoxia in vitro compared to control islets. Transplantation of shielded islets results in considerably earlier normoglycemia and vascularization, an enhanced glucose tolerance and a higher β-cell mass. Our results how that hAECs have a clear cytoprotective effect against hypoxic damages in vitro. This strategy improves β-cell mass engraftment and islet revascularization, leading to an improved capacity of islets to reverse hyperglycaemia, and could be rapidly applicable in the clinical situation seeing that the modification to human islets are minor.

Keywords
  • Basic (laboratory) research/science
  • Diabetes: type 1
  • Islet transplantation
  • Islets of Langerhans
  • Regenerative medicine
  • Stem cells
  • Tissue/organ engineering
  • Translational research/science.
Citation (ISO format)
LEBRETON, Fanny et al. Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model. In: American Journal of Transplantation, 2020. doi: 10.1111/ajt.15812
Main files (2)
Article (Accepted version)
accessLevelPublic
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1600-6135
223views
138downloads

Technical informations

Creation02/13/2020 10:39:00 AM
First validation02/13/2020 10:39:00 AM
Update time03/15/2023 9:53:25 PM
Status update03/15/2023 9:53:24 PM
Last indexation01/17/2024 9:44:53 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack