Modeling the thoracic aortic aneurysm in Loeys-Dietz syndrome with patient’s induced pluripotent stem cells (iPSCs)
Thoracic Aortic aneurysm and dissections account for 1-2% of all death in Western countries. no medical treatments is available. A subset of mutated genes that predispose patients to TAA and dissections (TAAD) are predicted to alter transforming growth factor b (TGF-b) signaling, but it is unknown how these mutations mechanistically affect TGF-b signaling and cause TAAD. Mutations in genes coding TGF-b receptors type I predispose to TAAD. We propose using human induced pluripotent stem cells (iPSCs) derived from normal patients to generate isogenic mutated iPSCs by introducing specific mutations of TGFBR1 with CRISPR Cas 9 technology. We will use those isogenic mutated iPSCs and iPSCs generated from TAAD patients to model TAAD by differentiating iPS cells into different SMC lineages in vitro and develop an in vivo model of TAAD with tissue engineered vessels using mutant iPSC-SMCs, and explore the medical treatment of TAAD .