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...
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MDPI AG
2025-03-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Mohsen Honarpisheh |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-984d236fc2cd4477883802e8041f3fad |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-984d236fc2cd4477883802e8041f3fad2025-08-20T02:53:19ZengMDPI AGCells2073-44092025-03-0114536610.3390/cells14050366Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic MiceMohsen Honarpisheh0Yutian Lei1Antonia Follenzi2Alessia Cucci3Cristina Olgasi4Ekaterine Berishvili5Fanny Lebreton6Kevin Bellofatto7Lorenzo Piemonti8Antonio Citro9Francesco Campo10Cataldo Pignatelli11Olivier Thaunat12Elisabeth Kemter13Martin Kraetzl14Eckhard Wolf15Jochen Seissler16Lelia Wolf-van Buerck17VANGUARD ConsortiumMedizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Universität München, LMU Munich, 80336 Munich, GermanyMedizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Universität München, LMU Munich, 80336 Munich, GermanyDepartment of Health Sciences, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Health Sciences, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyTissue Engineering and Organ Regeneration Lab, University of Geneva, Department of Surgery, CH-1211 Geneva, SwitzerlandTissue Engineering and Organ Regeneration Lab, University of Geneva, Department of Surgery, CH-1211 Geneva, SwitzerlandTissue Engineering and Organ Regeneration Lab, University of Geneva, Department of Surgery, CH-1211 Geneva, SwitzerlandDiabetes Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyDiabetes Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyDiabetes Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyDiabetes Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, ItalyCentre International de Recherche en Infectiologie, Université Claude Bernard Lyon I, 69364 Lyon, FranceMolecular Animal Breeding and Biotechnology, Gene Centre and Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, GermanyMolecular Animal Breeding and Biotechnology, Gene Centre and Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, GermanyMolecular Animal Breeding and Biotechnology, Gene Centre and Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, GermanyMedizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Universität München, LMU Munich, 80336 Munich, GermanyMedizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Universität München, LMU Munich, 80336 Munich, GermanyThe 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.https://www.mdpi.com/2073-4409/14/5/366xenotransplantationneonatal porcine islet-like cell clustersreaggregated cell clustersblood outgrowth endothelial cells |
| spellingShingle | 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 Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice Cells xenotransplantation neonatal porcine islet-like cell clusters reaggregated cell clusters blood outgrowth endothelial cells |
| title | Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice |
| title_full | Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice |
| title_fullStr | Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice |
| title_full_unstemmed | Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice |
| title_short | Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice |
| title_sort | spheroids composed of reaggregated neonatal porcine islets and human endothelial cells accelerate development of normoglycemia in diabetic mice |
| topic | xenotransplantation neonatal porcine islet-like cell clusters reaggregated cell clusters blood outgrowth endothelial cells |
| url | https://www.mdpi.com/2073-4409/14/5/366 |
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