Intelligent bioprocessing for haemotopoietic cell cultures using monitoring and design of experiments

The need for successful ex-vivo expansion and directed differentiation of haematopoietic stem cells (HSCs) for therapeutic applications has increased over the past decade. Haematopoietic cell cultures are complex and full characterisation of the process environment has yet to be achieved. The complexity and transient nature of HSC cultures make the identification, maintenance and control of optimal operating conditions challenging. Application of real-time, on-line monitoring techniques and process control strategies enhances the ability to operate bioprocesses of desired reproducibility and high product quality. In this review, we discussed the methods by which in vitro culture information necessary for bioprocess control may be obtained, including process considerations, monitoring and analytical tools, and design of experiments (DOE). The successful application of these tools may result in time- and cost-effective cultures for directed differentiation and expansion of haematopoietic components intended for clinical use.