A Novel Stirred Tank Bioreactor with Sequencing Batch Aeration System for Mass Production of Stem Cells: Conceptual Design,Modeling and Performance Analysis

Background and Aim: It is necessary to proliferate stem cells from thelow initial amounts to desirable values for use in regenerative medicine,cell therapies, and other medical/scientific applications. Regarding thevulnerability of these cells due to the lack of cell wall, it seems essentialto design processes which could provide appropriate conditions tomonitor and control the parameters influencing the growth. Hence, inthis study, an innovative cell culture system was designed with the goal ofreaching the maximum obtainable cell number on the base of simplicity,efficiency, and economic regards.Methods: At first, all of the effective parameters were defined and studied.Then the best conditions with respect to existing facilities were selectedfor designing an upgraded stirred bioreactor with a sequencing batchaeration system, in a way that it could attain to the final amounts needed by the patient, from small amounts of the initial biopsy in an economicalmanner. Finally, after writing related mass balances, modeling andsimulation were done to predict the possible behaviors of the system.Results: The overall volume of a bioreactor, required for both liquid andgas phases, were obtained equal to 400 mL. The novel bioreactor systemcan work with daily replacement of total gas phase (95% air/5% CO2,with 1% positive pressure), and the replacement of half of the liquidphase, three-day once with fresh medium. Ultimately according to thegraphs obtained from the simulation, it is concluded that in the designedbioreactor with explained sequencing batch aeration, the final numberof cells needed by the patient (about 2∈108 cells) could be achievedduring the 10-day cultivation without the problems caused by a shortageor critical accumulation of any materials.Conclusion: The novel designed economical bioreactor systemdemonstrated a great potential for mass production of stem cellsparticularly suspension stem cells, although further experiments areneeded to evaluate the real performance of the system for this purpose.

کلیدواژه ها:

Mammalian cells ، Proliferation ، Stirred bioreactor ، Sequencing batch process