Abstract 24044: Therapeutic Effects of human Pluripotent Stem Cell-derived Lymphatic Endothelial Cells encapsulated with Nanomatrix Gel on Experimental Lymphedema

Background: Current systems generating lymphatic endothelial cell (LEC) from human induced pluripotent stem cells (hPSCs) have limited value due to low purity, the use of undefined components for differentiation, and poor cell survival in vivo. Here, we developed a fully defined system to differentiate hPSCs into LECs and evaluated their therapeutic and engraftment potential when encapsulated in a nanomatrix gel (PA-RGDS). Methods and Results: hPSCs were cultured with GSK3β inhibitor on collagen-coated plates for 2-3 days to induce differentiation into the mesodermal lineage. The mesodermally differentiated cells were then cultured with VEGFC, VEGFA, EGF, and bFGF for another 6 days and double-sorted by PDPN and FLT4. These hPSC-PDPN+FLT4+ cells (hPSC-derived lymphatic endothelial cells, hPSC-LECs) showed highly purified and fully functional LEC characteristics in vitro. These hPSC-LECs express LEC markers such as PDPN, LYVE1, PROX1, and FLT4 at the mRNA level and the protein level, and formed tube-like s...