A novel 3D model that recapitulates human insulitis ex vivo - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2023

A novel 3D model that recapitulates human insulitis ex vivo

Résumé

Insulitis is a pathophysiological process characteristic of type 1 diabetes. Non-obese diabetic mice are the gold standard experimental model to investigate insulitis. However, species differences between rodent and humans, in many cases, preempt translational application. Many human tissue collections exist to investigate this process, in a non-dynamic manner. We have developed an ex vivo model to investigate the initiation and evolution of insulitis in human using patient-derived human islets from cadaveric donors. Pancreas and blood samples were obtained from brain-dead organ donors upon consent from the Biotherapy Platform of the CHU of Lille, France. Highly pure (> 90 % purity) freshly isolated islets were 3D-cultured in solubilized extracellular matrix gel. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples. Islets in coculture with same donor PBMCs, were incubated with cytokines (IL-1β, TNF-α, IFN-γ). We determined dynamic infiltration of immune cells directed to the islets over time. In our model, cytokines induced islet-directed immune cell infiltration starting as early as 18 hours and reaching maximum at 48 hours. Cytokines induced H2O2 and NO production in islets, and triggered cell death and apoptosis 24 hours after the insult. In this model, islets expressed higher levels of cytokines and chemokines when treated with the mix of cytokines. Islets also displayed beta cell dysfunction, measured as glucose-stimulated insulin secretion (GSIS) in a perifusion system, as early as 1 hour after the insult with cytokines, which was more accentuated 24 hours after. Altogether, this model can lead to better understanding of the landmarks of insulitis in human to decipher novel targets of interest, and aid in the discovery or testing of novel therapeutics.
Fichier non déposé

Dates et versions

hal-04537445 , version 1 (08-04-2024)

Identifiants

  • HAL Id : hal-04537445 , version 1

Citer

Elise Wreven, Valery Gmyr, María Soledad Ruiz de Adana, Francisco-Javier Bermudez-Silva, María Jose Vallejo Herrera, et al.. A novel 3D model that recapitulates human insulitis ex vivo. XXXIV Congreso de la Sociedad Espanola de Diabetes - Grupo de Investigacion de Islotes, Apr 2023, Valencia, Spain. ⟨hal-04537445⟩

Collections

RIIP UNIV-LILLE
13 Consultations
0 Téléchargements

Partager

Gmail Mastodon Facebook X LinkedIn More