TY - JOUR ID - 250712 TI - A Novel Insight into Endothelial and Cardiac Cells Phenotype in Systemic Sclerosis Using Patient-Derived Induced Pluripotent Stem Cell JO - Cell Journal (Yakhteh) JA - CELLJ LA - en SN - 2228-5806 AU - Gholami, Sedigheh AU - Mazidi, Zahra AU - Pahlavan, Sara AU - Moslem, Fariba AU - Hosseini, Mahya AU - Taei, Adeleh AU - Hesaraki, Mahdi AU - Barekat, Maryam AU - Aghdami, Nasser AD - .Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;.Department of Developmental Biology, University of Science and AD - .Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran AD - .Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Y1 - 2021 PY - 2021 VL - 23 IS - 3 SP - 273 EP - 287 KW - Angiogenesis KW - Cardiomyocyte KW - Induced Pluripotent Stem Cells KW - Systemic sclerosis KW - VE KW - Cadherin DO - 10.22074/cellj.2021.7244 N2 - ObjectiveSystemic sclerosis (SSc) is a connective tissue disease associated with vascular damage and multi organ fibrotic changes with unknown pathogenesis. Most SSc patients suffer from defective angiogenesis/vasculogenesis and cardiac conditions leading to high mortality rates. We aimed to investigate the cardiovascular phenotype of SSc by cardiogenic differentiation of SSc induced pluripotent stem cells (iPSC). Materials and MethodsIn this experimental study, we generated iPSC from two diffuse SSc patients, followed by successful differentiation into endothelial cells (ECs) and cardiomyocytes (CMs). ResultsSSc-derived EC (SSc-EC) expressed KDR, a nearly EC marker, similar to healthy control-EC (C1-EC). After sorting and culturing KDR+ cells, the resulting EC expressed CD31, a late endothelial marker, but vascular endothelial (VE)-cadherin expression markedly dropped resulting in a functional defect as reflected in tube formation failure of SSc-EC. Interestingly, upregulation of SNAI1 (snail family transcriptional repressor 1) was observed in SSc-EC which might underlie VE-cadherin downregulation. Furthermore, SSc-derived CM (SSc-CM) successfully expressed cardiac- specific markers including ion channels, resulting in normal physiological behavior and responsiveness to cardioactive drugs. ConclusionThis study provides an insight into impaired angiogenesis observed in SSc patients by evaluating in vitro cardiovascular differentiation of SSc iPSC. UR - https://www.celljournal.org/article_250712.html L1 - https://www.celljournal.org/article_250712_94e2c660a94900f53e39b39dbee7436a.pdf ER -