Integrated process design of passage culture and freezing for mesenchymal stem cells toward the establishment of working cell banks

This work presents an integrated process design of passage culture and freezing for mesenchymal stem cells (MSCs) toward the establishment of working cell banks for the cells. From a process modeling perspective, it is necessary to consider the impact of the passage culture process on the freezing process. Therefore, we adopted the cell diameter as the connecting parameter between the two processes. The cell diameter was expressed as a function of the cumulative population doubling level (cPDL) in the passage culture process model, and the freezing process model calculated the cell survival rate and the number of living cells after thawing using the cell diameter as the input. Given the number of passage operations, the days per passage, and the cooling rate of the freezer, the integrated process model can evaluate the cPDL, the cell survival rate, and the number of living cells after thawing. The application of the developed model was demonstrated in a case study. As a result, a feasible parameter range of working cell banks for MSCs was obtained, given a set of constraints that consisted of the cPDL, the cell survival rate, and the number of living cells after thawing. These results would be useful for designing working cell banks for MSCs.