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Ovine Model For Generation of Tissue-Engineered Vascularized Bone of Large Volume and Custom Geometry

Dilated cardiomyopathy (DCM) is a multivariate disease with poorly understood mechanisms, but recently 30+ different mutations have been suggested to contribute to disease pathology.

We have identified the first incidence where a family with high DCM prevalance is caused by the co-segregation of two heterozygous mutations in dissimilar cytoskeletal proteins, i.e. α-tropomyosin (TPM1; +/c.G97A) and vinculin (VCL; +/c.659dupA). To better understand the disease mechanism, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from the family cohort carrying the variants and modeled these variants in human embryonic stem cell-derived CMs (hESC-CMs) via RNAi and CRISPR to discern the functional consequences that could induce DCM.

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