Large-scale production of megakaryocytes in microcarrier supported stirred suspension bioreactors

Although extensive research has been dedicated to developing processes for differentiating PLTs from MKs, no sustainable process for large-scale MK production is available. This study aimed at developing an effective, xeno-free and scalable system to produce high numbers of MKs. In particular, microcarrier beads-assisted stirred bioreactors were evaluated as a means of improving MK yields. This method resulted in the production of 18.7 Å~ 107 MKs per 50 ml medium. Biolaminin 521-coated microcarriers increased MK production per iPSC by up to 10-fold. MKs obtained in this system showed typical features of mature MKs and were able to produce PLTs in vitro and in vivo. To increase safety, MKs produced in the bioreactors were irradiated; a procedure that did not affect their capability to form proPLTs and PTLs after transfusion.