01895nas a2200337 4500000000100000000000100001008004100002260001500043653002700058653002200085653004100107653002400148653002200172100001400194700001600208700002100224700002500245700001500270700002300285700002500308700001800333700001800351700001700369700001500386700002100401700001500422245012600437856004700563520093300610022001401543 2025 d c2025-09-2510aCapillary Malformation10aEndothelial Cells10ahuman induced pluripotent stem cells10aSmooth Muscle Cells10aVascular Organoid1 aVi Nguyen1 aAnna Harper1 aMackenzie Azuero1 aIsabella Castellanos1 aSiwuxie He1 aMarcelo L. Hochman1 aCamilla F. Wenceslau1 aDong-bao Chen1 aAnil G. Jegga1 aYunguan Wang1 aDaping Fan1 aJ. Stuart Nelson1 aWenbin Tan00aVascular Organoids Derived from Capillary malformation-induced Pluripotent Stem Cells Exhibit Disease-Relevant Phenotypes uhttps://doi.org/10.1007/s12015-025-10984-83 aCapillary malformation (CM) is a congenital vascular anomaly that affects the skin, mucosa, eye, and brain. A major obstacle to mechanistic and drug screening studies for CM has been the lack of preclinical models. In this study, we established vascular organoids (VOs) generated through the self-assembly of vascular lineages of endothelial cells and smooth muscle cells differentiated from CM-induced pluripotent stem cells (iPSC). Within these VOs induced endothelial cells and smooth muscle cells organized into juxtapositions to form vascular branches. CM patient iPSC-derived VOs showed a higher density of endothelial and smooth muscle cell populations and greater vascular branch lengths as compared with VOs derived from iPSCs generated from healthy skin biopsies. Overall, this study represents the first disease-relevant VO model of CM, providing a valuable platform for future mechanistic studies and drug screening. a2629-3277