Chapter 2 - Process development and manufacturing approaches for mesenchymal stem cell therapies

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The emergence of cell and gene therapies (CGTs) as a novel therapeutic modality has ushered in significant scope and opportunity to address previously unmet need. The rationale behind such therapies is to use cells, somatic, or modified/reprogrammed, to trigger regeneration of damaged tissues or targeting of cancer cells, for example. With increasing numbers of CGT products receiving regulatory approval, there is now a focus on establishing scalable and robust manufacturing processes for both autologous (patient-specific) and allogeneic (universal donor) which are both cost effective and can meet expected demand. One of the cell types under evaluation in numerous clinical trials is human mesenchymal stem/stromal cells (hMSCs) that possess both immunomodulatory properties and in vitro differentiation capability. These properties have been explored for conditions such as graft-versus host disease (GvHD), acute myocardial infarction (AMI), and Crohn’s disease among others. One of the current engineering challenges for hMSC-based products is to generate clinically relevant numbers of cells to meet the dose criteria while retaining the product’s critical quality attributes (CQAs). Traditional planar-based culture systems have several disadvantages such as low scalability, limited control and are highly dependent on human handling. Significant research and development activity has focused on establishing scalable and controlled bioprocesses for hMSC expansion that keep the cells’ biological properties. This chapter focuses on the discussion of the various options that manufacturers face during each stage of the hMSC from isolation, to expansion, downstream processing, and finally the product formulation.