Meticulous optimization of cardiomyocyte yields in a 3-stage continuous integrated agitation bioprocess

Publication date: Available online 1 August 2018Source: Stem Cell ResearchAuthor(s): Sherwin Ting, Alan Lam, Gerine Tong, Allen Chen, Heming Wei, JianJun Wu, Yue Ning Lam, Shaul Reuveny, Steve OhAbstractHuman pluripotent stem cells (hPSCs) can be a renewable source for generating cardiomyocyte (CM) for treating myocardial infraction. In our previous publication, we described an integrated microcarrier-based wave reactor process for the expansion and differentiation of hPSCs to CMs on a rocker based platform. However, this platform is limited in terms of linear scalability and CMs purity. The present study describes ways to overcome these limitations by the use of a stirred scalable platform and incorporation of an additional lactate based purification step which increases CM purity.Efficient CM differentiation in stirred spinners was achieved by (1) Addition of ascorbic acid (AS) during the differentiation phase which resulted in an increase of 38.42% in CM yield (0.84 ± 0.03 × 106vs 1.17 ± 0.07 × 106 CM/mL for cultures without AS and with AS respectively) and (2) Change of agitation regime to a shorter static intervals one (from 66 min off/6 min on (66/6) to 8 min off/1 min on (8/1)) during the first 3 days of differentiation which resulted in 22% increase in CM yield (1.50 ± 0.10 × 106vs 1.23 ± 0.07 × 106 CM/mL). The combination of AS addition and change in agitation regime resulted in a production yield of 1.50 ± 0...
Source: Stem Cell Research - Category: Stem Cells Source Type: research