{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:25:36Z","timestamp":1792009536282,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":343,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n                    Human induced pluripotent stem cell (iPSC)\u2013derived endothelial cells (ECs) have emerged as a promising source of autologous cells with great potential to produce novel cell therapy for ischemic vascular diseases. However, their clinical application still faces numerous challenges including safety concerns such as the potential aberrant immunogenicity derived from the reprogramming process. This study investigated immunological phenotypes of iPSC\u2010ECs by a side\u2010by\u2010side comparison with primary human umbilical vein ECs (HUVECs). Three types of human iPSC\u2010ECs, NIBSC8\u2010EC generated in house and two commercial iPSC\u2010ECs, alongside HUVECs, were examined for surface expression of proteins of immune relevance under resting conditions and after cytokine activation. All iPSC\u2010EC populations failed to express major histocompatibility complex (MHC) Class II on their surface following interferon\u2010gamma (IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    ) treatment but showed similar basal and IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    \u2010stimulated expression levels of MHC Class I of HUVECs. Multiple iPSC\u2010ECs also retained constitutive and tumor necrosis factor\u2010alpha (TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    )\u2010stimulated expression levels of intercellular adhesion molecule\u20101 (ICAM\u20101) like HUVECs. However, TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    induced a differential expression of E\u2010selectin and vascular cell adhesion molecule\u20101 (VCAM\u20101) on iPSC\u2010ECs. Furthermore, real\u2010time monitoring of proliferation of human peripheral blood mononuclear cells (PBMCs) cocultured on an endothelial monolayer over 5 days showed that iPSC\u2010ECs provoked distinct dynamics of PBMC proliferation, which was generally decreased in alloreactivity and IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    \u2010stimulated proliferation of PBMCs compared with HUVECs. Consistently, in the conventional mixed lymphocyte reaction (MLR), the proliferation of total CD3+ and CD4+ T cells after 5\u2010day cocultures with multiple iPSC\u2010EC populations was largely reduced compared to HUVECs. Last, multiple iPSC\u2010EC cocultures secreted lower levels of proinflammatory cytokines than HUVEC cocultures. Collectively, iPSC\u2010ECs manifested many similarities, but also some disparities with a generally weaker inflammatory immune response than primary ECs, indicating that iPSC\u2010ECs may possibly exhibit hypoimmunogenicity corresponding with less risk of immune rejection in a transplant setting, which is important for safe and effective cell therapies.\n                  <\/jats:p>","DOI":"10.1155\/sci\/6153235","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T10:35:37Z","timestamp":1733740537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Human iPSC\u2013Derived Endothelial Cells Exhibit Reduced Immunogenicity in Comparison With Human Primary Endothelial 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