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 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.
Authors
- Lorenzo Piemonti (ORCID: https://orcid.org/0000-0002-2172-2198)
- Jochen Seißler (ORCID: https://orcid.org/0000-0002-7404-2364)
- Francesco Campo (ORCID: https://orcid.org/0000-0001-5609-8084)
- Lelia Wolf‐van Buerck (ORCID: https://orcid.org/0009-0003-8468-6416)
- Alessia Cucci (ORCID: https://orcid.org/0000-0002-5003-831X)
- Mohsen Honarpisheh (ORCID: https://orcid.org/0000-0003-3002-7442)
- Eckhard Wolf (ORCID: https://orcid.org/0000-0002-0430-9510)
- Elisabeth Kemter (ORCID: https://orcid.org/0000-0001-7785-7502)
- Antonio Citro
- Kevin Bellofatto (ORCID: https://orcid.org/0000-0001-7961-4539)
- Fanny Lebreton (ORCID: https://orcid.org/0000-0002-3175-0205)
- Martin Kraetzl (ORCID: https://orcid.org/0000-0002-8449-177X)
- Yutian Lei (ORCID: https://orcid.org/0000-0001-6552-7645)
- Ekaterine Berishvili (ORCID: https://orcid.org/0000-0002-7969-1937)
- Olivier Thaunat (ORCID: https://orcid.org/0000-0002-3648-8963)
- Antonia Follenzi (ORCID: https://orcid.org/0000-0001-9780-300X)
- Cristina Olgasi (ORCID: https://orcid.org/0000-0002-5738-213X)
- Cataldo Pignatelli (ORCID: https://orcid.org/0000-0002-4231-0504)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- University of Geneva (CH)
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Vita-Salute San Raffaele University (IT)
- LMU Klinikum (DE)
- Hospices Civils de Lyon (FR)
- IRCCS Ospedale San Raffaele (IT)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Centre International de Recherche en Infectiologie (FR)
- Heinrich Heine University Düsseldorf (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Cells
- Published
- 2025-03-02
- DOI
- https://doi.org/10.3390/cells14050366
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- European Commission
- Deutsche Forschungsgemeinschaft