Honarpisheh Mohsen, Lei Yutian, Follenzi Antonia, Cucci Alessia, Olgasi Cristina, Berishvili Ekaterine, Lebreton Fanny, Bellofatto Kevin, Piemonti Lorenzo, Citro Antonio, Campo Francesco, Pignatelli Cataldo, Thaunat Olivier, Kemter Elisabeth, Kraetzl Martin, Wolf Eckhard, Seissler Jochen, Wolf-van Buerck Lelia
Medizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Universität München, LMU Munich, 80336 Munich, Germany.
Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy.
Cells. 2025 Mar 2;14(5):366. doi: 10.3390/cells14050366.
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 (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) ( < 0.05). Furthermore, intragraft vascular density was substantially increased ( < 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.
移植胰岛的植入取决于新血管网络的快速建立。本研究评估了脐血来源的血液内皮祖细胞（BOECs）对新生猪胰岛（NPIs）活力以及移植后NPIs移植物结局的影响。将分散的NPIs和人BOECs在微孔细胞培养板上重新聚集，并通过qRT-PCR和免疫组织化学检测它们的抗凋亡和促血管生成能力。将其移植到糖尿病NOD-SCID IL2rγ（NSG）小鼠体内后分析其体内功能。包含重新聚集的新生猪胰岛细胞（REPIs）和BOECs的球体在体外表现出增强的活力以及VEGFA、血管生成素-1、血红素加氧酶-1和TNFAIP3（A20）基因表达的显著升高。与仅移植REPI的组相比，移植球体的动物中正常血糖的发展明显更快（中位数分别为51.5天和60天）（<0.05）。此外，移植物内血管密度显著增加（<0.01）。预血管化的REPI-BOEC球体的共移植导致了更好的血管生成和加速的体内功能。这些发现可能为提高猪胰岛异种移植的疗效提供一种新工具。
