a, Schematic for isolation of large EV pellets (lEV-Ps), small EV pellets (sEV-Ps), exomeres and supermeres. Serum-free conditioned medium is centrifuged (500g and 2000g) to remove dead cells, cellular debris and apoptotic bodies. The lEV-P is obtained after centrifugation of the supernatant at 10,000g centrifugation for 40 min. The leftover supernatant is first concentrated and then subjected to ultracentrifugation at 167,000g for 4 h to obtain the sEV-P (washed one time in PBS by ultracentrifugation at 167,000g for 4 h). The supernatant from the previous step is centrifuged at 167,000g for 16 h to isolate the exomeres (washed one time in PBS by ultracentrifugation at 167,000g for 16 h). The supernatant from the previous step is centrifuged at 367,000g for 16 h to isolate supermeres. b, Representative photographs of the most important steps during the concentrator procedure from a.