bims-hummad Biomed News
on Humanised mouse models of autoimmune disorders
Issue of 2025–12–28
two papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Vascularization of Human Pancreatic Islets With Adaptive Endothelial Cells for In Vitro Analysis and In Vivo Transplantation.
  2. Engineered extracellular vesicles reprogram T cells by targeting PD-1 and PHB1 signaling in inflammatory bowel disease.
  1. Bio Protoc. 2025 Dec 20. 15(24): e5550
    Vascularization of Human Pancreatic Islets With Adaptive Endothelial Cells for In Vitro Analysis and In Vivo Transplantation.
    Ge Li, Rebecca Craig-Schapiro, Ahsan Uddin, Shahin Rafii.
      The pancreatic islet, the only type of tissue that secretes insulin in response to elevated blood glucose, plays a vital role in diabetes development and treatment. While various islet vascularization strategies have been developed, they have been hindered by major limitations such as relying on pre-patterning and the inability to span long distances. Furthermore, few strategies have demonstrated robust enough vascularization in vivo to support therapeutic subcutaneous islet transplantation. Using adaptive endothelial cells (ECs) reprogrammed by transient expression of the ETS Variant Transcription Factor 2 (ETV-2) gene, we have physiologically vascularized human islets within a generic microchamber and have achieved functional engraftment of human islets in the subcutaneous space of mice. Such adaptive ECs, which we term reprogrammed vascular ECs (R-VECs), have been proven to be a suitable tool for both in vitro disease modeling and in vivo transplantation of not only islets but also other organoids. Key features • This protocol contains two parts: the in vitro and in vivo parts, both utilizing adaptable endothelial cells to functionally vascularize human islets. • The in vitro portion of this protocol describes the method to culture human islets in a vascular bed within a large and commercially available microchamber. • The in vivo portion of this protocol provides a step-by-step procedure to reverse hyperglycemia in streptozotocin-induced diabetic mice.
    Keywords:  Diabetes; Insulin secretion; Pancreatic islet; Subcutaneous transplantation; Vascularization
    DOI:  https://doi.org/10.21769/BioProtoc.5550
  2. Signal Transduct Target Ther. 2025 Dec 25. 10(1): 418
    Engineered extracellular vesicles reprogram T cells by targeting PD-1 and PHB1 signaling in inflammatory bowel disease.
    Mi-Kyung Oh, Hyun Sung Park, Dong-Hoon Chae, Aaron Yu, Jae Han Park, Jiyoung Heo, Keonwoo Cho, Jiho Kim, Byeonghwi Lim, Jun-Mo Kim, Jordan E Axelrad, Kyung Ku Jang, Jong Pil Im, Seong-Joon Koh, Byung-Soo Kim, Kyung-Rok Yu.
      Current therapies for inflammatory bowel disease (IBD) often fail to achieve complete remission and are associated with systemic toxicity owing to their broad immunosuppressive effects. To overcome these limitations, we developed a bioengineered extracellular vesicle (EV) platform that modulates key immune signaling pathways to efficiently restore the T-cell balance in inflamed intestinal tissues. EVs derived from Wharton's jelly mesenchymal stem cells were engineered to display PD-L1 on their surface and encapsulate miR-27a-3p. Surface PD-L1 engages the PD-1 checkpoint in activated T cells, attenuating T-cell receptor signaling via SHP2-mediated dephosphorylation of ZAP70 and AKT. In parallel, miR-27a-3p suppresses prohibitin 1 (PHB1), a mitochondrial regulator of Th17 cell bioenergetics and inflammatory function, thereby reducing Th17 polarization and increasing the number of FOXP3⁺ regulatory T cells. These dual-targeting EVs preferentially localized to inflamed intestinal tissues via chemokine (CCR2/CXCR4) and PD-1-dependent mechanisms. In humanized mouse models of colitis, these EVs attenuated mucosal inflammation, suppressed effector T-cell responses, and preserved epithelial integrity. In IBD patient-derived colonoid cultures, PD-L1/miR-27a-3p EVs maintained epithelial viability and barrier integrity without inducing cytotoxicity or structural disruption. Transcriptomic and single-cell analyses revealed the downregulation of inflammatory and exhaustion signatures, along with the enrichment of regulatory subsets. Collectively, this study presents a cell-free immunotherapeutic approach that reprograms T cells in inflamed tissues through the PD-1 and mitochondrial signaling pathways while maintaining intestinal epithelial integrity, offering a promising therapeutic strategy for IBD and other T cell-driven inflammatory disorders.
    DOI:  https://doi.org/10.1038/s41392-025-02516-0
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