@article{farber_dong_wang_rathod_wang_dixit_keepers_xie_butz_polacheck_et al._2024, title={Direct conversion of cardiac fibroblasts into endothelial-like cells using <i>Sox17</i> and <i>Erg</i>}, volume={15}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-024-48354-6}, abstractNote={Endothelial cells are a heterogeneous population with various organ-specific and conserved functions that are critical to organ development, function, and regeneration. Here we report a Sox17-Erg direct reprogramming approach that uses cardiac fibroblasts to create differentiated endothelial cells that demonstrate endothelial-like molecular and physiological functions in vitro and in vivo. Injection of these induced endothelial cells into myocardial infarct sites after injury results in improved vascular perfusion of the scar region. Furthermore, we use genomic analyses to illustrate that Sox17-Erg reprogramming instructs cardiac fibroblasts toward an arterial-like identity. This results in a more efficient direct conversion of fibroblasts into endothelial-like cells when compared to traditional Etv2-based reprogramming. Overall, this Sox17-Erg direct reprogramming strategy offers a robust tool to generate endothelial cells both in vitro and in vivo, and has the potential to be used in repairing injured tissue.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Farber, Gregory and Dong, Yanhan and Wang, Qiaozi and Rathod, Mitesh and Wang, Haofei and Dixit, Michelle and Keepers, Benjamin and Xie, Yifang and Butz, Kendall and Polacheck, William J. and et al.}, year={2024}, month={May} }
 @article{rathod_aw_huang_lu_doherty_whithworth_xi_roy-chaudhury_polacheck_2024, title={Donor-Derived Engineered Microvessels for Cardiovascular Risk Stratification of Patients with Kidney Failure}, ISSN={["1613-6829"]}, DOI={10.1002/smll.202307901}, abstractNote={AbstractCardiovascular disease is the cause of death in ≈50% of hemodialysis patients. Accumulation of uremic solutes in systemic circulation is thought to be a key driver of the endothelial dysfunction that underlies elevated cardiovascular events. A challenge in understanding the mechanisms relating chronic kidney disease to cardiovascular disease is the lack of in vitro models that allow screening of the effects of the uremic environment on the endothelium. Here, a method is described for microfabrication of human blood vessels from donor cells and perfused with donor serum. The resulting donor‐derived microvessels are used to quantify vascular permeability, a hallmark of endothelial dysfunction, in response to serum spiked with pathophysiological levels of indoxyl sulfate, and in response to serum from patients with chronic kidney disease and from uremic pigs. The uremic environment has pronounced effects on microvascular integrity as demonstrated by irregular cell–cell junctions and increased permeability in comparison to cell culture media and healthy serum. Moreover, the engineered microvessels demonstrate an increase in sensitivity compared to traditional 2D assays. Thus, the devices and the methods presented here have the potential to be utilized to risk stratify and to direct personalized treatments for patients with chronic kidney disease.}, journal={SMALL}, author={Rathod, Mitesh L. and Aw, Wen Yih and Huang, Stephanie and Lu, Jingming and Doherty, Elizabeth L. and Whithworth, Chloe P. and Xi, Gang and Roy-Chaudhury, Prabir and Polacheck, William J.}, year={2024}, month={Jan} }