Please join us for this month's webinar with Donny Hanjaya-Putra, Ph.D., Associate Professor at the University of Notre Dame. The title of his talk is Engineering Blood and Lymphatic Vasculatures Using Stem Cells and Biomaterials.
Abstract: Stem cells respond to many cues from their microenvironment, including chemical and mechanical signals. These important cues can be incorporated into biomaterials to control stem cell differentiation and morphogenesis for the regeneration of the circulatory system. Here, we discuss our recent efforts to design synthetic biomaterials as a modular platform to direct stem cell fate and morphogenesis toward the formation of blood and lymphatic vasculatures.
First, we have used multilamellar lipid nanoparticles to rejuvenate cord blood-derived endothelial colony-forming cells (ECFCs) and improve their therapeutic potential. By controlling the release kinetics of various bioactive molecules at the surface of ECFCs, we not only improve cell migration but also augment their angiogenic potential in vitro and in vivo. Second, we used a stepwise differentiation protocol to direct human pluripotent stem cells into lymphatic endothelial cells. We observed that treatment with sodium acetate, an acetyl-CoA precursor, increases the expression of the lymphatic master regulator gene Prox1, indicating the activation of a positive feedback loop between VEGFR3 and Prox1.
Finally, we have used hyaluronic acid (HA)-based hydrogels to promote lymphatic network formation. By tuning the mechanical properties of the hydrogels, we have demonstrated that HA-based hydrogels preserve key lymphatic phenotypes and that matrix stiffness primes lymphatic tube formation in response to VEGF-C. In murine lymphedema models, engineered lymphatic networks integrated with host lymphatic vessels and reduced tissue swelling, further supporting their potential use in regenerative therapies targeting the lymphatic system.
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