Fig. 6

Sprouting cells from MPC-derived spheroids acquire endothelial tip cell-like features. Analyzing the invading front of MPC spheroids, most cells at the distal ends of invading branches showed the bipolar morphology characteristic of endothelial “tip cells” (a). Cells harvested from enzymatic digestion of sprouted MPC spheroids acquired the ability to form CLS with numerous closed pseudo-lumens (b, black arrows; three representative samples displayed), although showing smaller lumen mean areas than HUVECs (c). Many “tip cell-like” invading cells were still detectable after MPC spheroid enzymatic digestion (b, white arrows). Gene expression analysis confirmed MPC-related gene (SPP1 and NES) downregulation together with activation of genes involved in angiogenic and lymphoangiogenic sprouting as TEM1, FLT-4, PROX-1, and DLL4 (d). *p < 0.05, **p < 0.01, ***p < 0.001. HUVEC human umbilical vein endothelial cell, MPC mesangiogenic progenitor cell, N.D. not detected