Technologies for large-scale umbilical cord-derived MSC expansion: Experimental performance and cost of goods analysis

The translation of cell therapies into clinical practice requires a scalable, efficient and cost-effective manufacturing process. This paper presents an integrated experimental and cost analysis of different cell culture technologies for umbilical cord-derived mesenchymal stromal/stem cell expansion: a multi-layer vessel (ML), a stirred tank bioreactor with microcarrriers (STR), a hollow fiber bioreactor (HF) and a packed-bed bioreactor (PB). The results showed that the cell proliferation rate, expansion fold and harvesting efficiency were highest in HF (36.8 ± 1.7 h; 9.8 ± 1.0 −fold; 100%). The STR, ML and PB achieved a similar level of cell number with high expansion folds (8.8 ± 0.39, 8.7 ± 0.90, 6.9 ± 1.3 −fold, respectively). However, harvesting efficiency was lowest with PB (18% ± 0.77), followed by STR (61% ± 15.7). The cells retained their functional properties post culture in all the technologies evaluated. The experimental results were incorporated into an advanced decisional tool comprising a bioprocess economics model and a stochastic model so as to evaluate the commercial economic feasibility and robustness of different candidate technologies for MSC manufacture. The model predicted that HF would be the least cost-effective option despite its advantageous experimental performance, due to its high consumable and equipment costs. ML ranked first in cost-effectiveness and robustness in this scenario followed by STR. The results also demonstrated how the bioprocess economics model can be used to direct improvements to the culture platforms so as to achieve commercial success according to the reimbursement level.