[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-447663-105":59,"doc-detail-447663-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","nurturing-protectors-macrophages-in-the-human-pancreatic-islet","Nurturing protectors: Macrophages in the human pancreatic islet","","Nurturing protectors: Macrophages in the human pancreatic islet discusses how two Cell Stem Cell studies used pluripotent stem cell-derived co-culture systems to define macrophage roles in pancreatic islet development and disease. It outlines islet structure and glucoregulatory cell types, then summarizes how SARS-CoV-2 and CVB4 infection increases inflammatory macrophages and pyroptosis pathways, and how developmental fetal macrophage–endocrine signaling (eMACEndo) enhances β-cell output and C-peptide secretion in engrafted mice.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nurturing-protectors-macrophages-in-the-human-pancreatic-islet/447663/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/nurturing-protectors-macrophages-in-the-human-pancreatic-islet/447663.png","ImageObject",300,407,{"name":92,"@type":93},"dabgoudw","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the purpose of using pluripotent stem cell-derived co-culture systems in these studies?","Question",{"text":112,"@type":113},"They are used to model and investigate how macrophages influence pancreatic islet behavior during development and under disease conditions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What did the Yang et al. study find regarding COVID-19 patient samples?",{"text":117,"@type":113},"It reported accumulation of proinflammatory macrophages within islets in COVID-19 samples, alongside decreased insulin+ endocrine cells without reduced overall islet area.",{"name":119,"@type":110,"acceptedAnswer":120},"How does eMACEndo relate to β-cell formation and function?",{"text":121,"@type":113},"eMACEndo organoids, formed by co-developing PSC-derived macrophages with pancreatic endoderm cultures, increased β-cell numbers and produced human C-peptide upon engraftment into immunocompromised mice.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},447663,1790779379,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":19,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":52,"preview_page_count":4},3985747860484,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Europe PMC unders uthManuscripts Europe M eC und Author Manuscripts  \n| Europe PMC Funders Group\u003Cbr>Author Manuscript\u003Cbr>Cell Stem Cell. Author manuscript; available in PMC 2026 January 06. |\n| --- |\n| Published in final edited form as:\u003Cbr>Cell Stem Cell. 2024 November 07; 31(11): 1553–1554. doi:10.1016/j.stem.2024.10.006 .\u003Cbr>Nurturing protectors: Macrophages in the human pancreatic islet Christopher Z.W. Lee 1 , Francesca M. Spagnoli 1,*\u003Cbr>1Centre for Gene Therapy and Regenerative Medicine, King’s College London, London, Great Maze Pond,, London SE1 9RT, UK.\u003Cbr>Abstract\u003Cbr>Two recent publications in Cell Stem Cell, Yang et al.1 and Migliorini et al.,2 utilized pluripotent stem cell-derived co-culture systems to explore the role of macrophages within the pancreatic islet during development and disease states.\u003Cbr>The pancreas is a heterocrine gland, responsible for the exocrine secretion of digestive enzymes in the duodenum and the endocrine secretion of various essential blood glucoseregulating hormones. The exocrine compartment of the pancreas comprises most of the tissue (>95%), whereas endocrine cells are scattered throughout and around the remaining tissue, arranged in distinctive structures known as the islets of Langerhans. These islets constantly monitor and adjust blood glucose levels via the production of glucagon from α cells, insulin from β cells, and, to a lesser extent, somatostatin from δ cells.3\u003Cbr>Immune cells, including macrophages, are also present in the pancreatic islets from the embryonic stage onward as part of the islet microenvironment.4,5 Besides the interplay between the immune system and pancreatic β cells in the context of type 1 diabetes (T1D),6 little is known about this intercellular crosstalk in other contexts. In this issue of Cell Stem Cell, Yang et al.1 and Migliorini et al.2 independently developed human pluripotent stem cell (PSC)-derived macrophage-containing islet culture systems, albeit using them to answer distinct questions in disease and development, respectively.\u003Cbr>In the study by Yang et al., 1 the authors developed a vascularized macrophageislet (VMI) organoid model for studying macrophage-mediated host damage. First, using the GeoMx spatial transcriptomics platform on pancreatic autopsy samples from patients with COVID-19 and healthy controls, they unveiled an accumulation of proinflammatory macrophages within the islets of the COVID-19 pancreatic samples, alongside a decrease in the number of insulin+ endocrine cells without a decrease in the overall islet area. Next, they performed single-cell RNA sequencing on human cadaveric islets infected with either SARS-CoV-2 or coxsackievirus B4 (CVB4) viruses and noticed an upregulation of the pyroptotic pathway in the islet endocrine cells of both virus-infected groups. This finding suggested that pyroptosis might be related to the activity of inflammatory macrophages.\u003Cbr>This work is licensed under a BY 4.0 International license.\u003Cbr>*Correspondence: [francesca.spagnoli@kcl.ac.uk](francesca.spagnoli@kcl.ac.uk).\u003Cbr>Declaration of interests\u003Cbr>The authors declare no competing interests |\n\nEurope PMC unders uthManuscripts Europe M eC und Author Manuscripts  \nLee and Spagnoli Page 2  \nTo test this hypothesis, they generated a PSC-derived VMI organoid model consisting of endocrine cells, endothelial cells, and macrophages and confirmed that TNF superfamily member 12 (TNFSF12) and interleukin-1beta (IL1B) were synergistically responsible for macrophage-mediated β cell pyroptosis.  \nMigliorini et al.2 approached the relevance of islet-macrophage intercellular crosstalk from a developmental point of view. The authors generated a transcriptomic map of the developing fetal human pancreas—14-and 18-week post-conception (WPC)—using single-nuclei RNA sequencing, and characterized the composition and heterogeneity of the exocrine, endocrine, and hematopoietic compartments. Next, they decided to zoom in on the macrophages, as among the hematopoieti","cbCaihCQEYKde1xP","https://ap.wps.com/l/cbCaihCQEYKde1xP","pdf",274727,"English","# Abstract\n## Pancreatic islet microenvironment and glucoregulation\n## Macrophage involvement in development and disease\n## Vascularized macrophage–islet organoid (VMI)\n## Developmental macrophage–endocrine cross-talk (eMACEndo)\n## Importance of islet biology communication","[{\"question\":\"What is the purpose of using pluripotent stem cell-derived co-culture systems in these studies?\",\"answer\":\"They are used to model and investigate how macrophages influence pancreatic islet behavior during development and under disease conditions.\"},{\"question\":\"What did the Yang et al. study find regarding COVID-19 patient samples?\",\"answer\":\"It reported accumulation of proinflammatory macrophages within islets in COVID-19 samples, alongside decreased insulin+ endocrine cells without reduced overall islet area.\"},{\"question\":\"How does eMACEndo relate to β-cell formation and function?\",\"answer\":\"eMACEndo organoids, formed by co-developing PSC-derived macrophages with pancreatic endoderm cultures, increased β-cell numbers and produced human C-peptide upon engraftment into immunocompromised mice.\"}]","Nurturing protectors: Macrophages in the human pancreatic islet | PDF",1790722111]