Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice

Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice

The engraftment of transplanted islets depends on the rapid establishment of a novel vascular network. The present study evaluated the effects of cord blood-derived blood outgrowth endothelial cells (BOECs) on the viability of neonatal porcine islets (NPIs) and the post-transplant outcome of grafted...

Full description

Saved in:
Bibliographic Details
Main Authors: Mohsen Honarpisheh, Yutian Lei, Antonia Follenzi, Alessia Cucci, Cristina Olgasi, Ekaterine Berishvili, Fanny Lebreton, Kevin Bellofatto, Lorenzo Piemonti, Antonio Citro, Francesco Campo, Cataldo Pignatelli, Olivier Thaunat, Elisabeth Kemter, Martin Kraetzl, Eckhard Wolf, Jochen Seissler, Lelia Wolf-van Buerck, VANGUARD Consortium
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
Subjects:
xenotransplantation
neonatal porcine islet-like cell clusters
reaggregated cell clusters
blood outgrowth endothelial cells
Online Access:https://www.mdpi.com/2073-4409/14/5/366
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The engraftment of transplanted islets depends on the rapid establishment of a novel vascular network. The present study evaluated the effects of cord blood-derived blood outgrowth endothelial cells (BOECs) on the viability of neonatal porcine islets (NPIs) and the post-transplant outcome of grafted NPIs. Dispersed NPIs and human BOECs were reaggregated on microwell cell culture plates and tested for their anti-apoptotic and pro-angiogenic capacity by qRT-PCR and immunohistochemistry. The in vivo functionality was analyzed after transplantation into diabetic NOD-SCID IL2rγ<sup>−/−</sup> (NSG) mice. The spheroids, which contained reaggregated neonatal porcine islet cells (REPIs) and BOECs, exhibited enhanced viability and a significantly elevated gene expression of VEGFA, angiopoetin-1, heme oxygenase-1, and TNFAIP3 (A20) in vitro. The development of normoglycemia was significantly faster in animals transplanted with spheroids in comparison to the only REPI group (median 51.5 days versus 60 days) (<i>p</i> < 0.05). Furthermore, intragraft vascular density was substantially increased (<i>p</i> < 0.01). The co-transplantation of prevascularized REPI-BOEC spheroids resulted in superior angiogenesis and accelerated in vivo function. These findings may provide a novel tool to enhance the efficacy of porcine islet xenotransplantation.
ISSN:2073-4409

Similar Items