In another study, iPSCs derived from skin biopsies of patients using either three (OSK) or four (OKSM) lentiviral factors were allowed to commence differentiation into DA neurons via dual SMAD inhibition for 1 day and feeder-free floor plate induction (Devine et al., 2011). Noggin (an inhibitor of BMP4) and SB431542 (an inhibitor of Lefty/Activin/TGFβ pathways) were used for this purpose, in addition to Dorsomorphin (a chemical BMP inhibitor) which acts as a partial substitute for Noggin. This was followed by SHH, WNT1, and Dickkopf WNT signaling pathway inhibitor 1 (Dkk1) blocking antibody treatment for 8 days, then switching the culture conditions to promote maturation of mDA neurons from neural progenitors (Devine et al., 2011).
