Abstract 17015: Lymphangioleiomyomatosis (LAM)-Induced Pluripotent Stem Cell (iPSC) Derived Smooth Muscle Cells Destabilze Capillary-Like Networks and Disrupt Angiogenic Gene Expression in Co-Culture With Endothelial Cells
Circulation(2017)
摘要
Background: During angiogenesis, healthy smooth muscle cells (SMCs) stabilize newly formed endothelial cell (EC) tubes and maintain vascular homeostasis. However, LAM smooth muscle-like cells invade the lung and compromise respiratory function which is dependent on a normal vascular and airway structure. Hence, we hypothesized that SMCs derived from LAM patients (LAM-iSMC) will disrupt, rather than stabilize, EC capillary like networks. Methods/Results: iPSCs were differentiated into SMCs (iSMCs) using embryoid body protocol. Co-culture of healthy iSMCs with HUVECs on Matrigel significantly increased the persistence of capillary-like networks to 72Hrs. In contrast, co-culture with LAM-iSMC led to premature network collapse (u003c15Hrs). EC were separated from iSMCs after 24-72 hours of co-culture by CD144+ immunomagnetic-selection and the expression of endothelial (eNOS, TIE2, KLF2, CD34) and angiogenic (VEGFA, ANGPT2) genes was assessed by qRT-PCR. Co-cultured with healthy iSMCs resulted in a 2 to 5-fold inc...
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