Quality Manufacturing of Mesenchymal Stem/Stromal Cells Using Scalable and Controllable Bioreactor Platforms
Human mesenchymal stem cells (hMSCs), also known as mesenchymal stromal cells, have demonstrated important therapeutic properties and hold great promise for the treatment of a broad range of debilitating medical conditions. As hMSC therapies move toward commercialization, the prime focus of the field is to develop robust biomanufacturing platforms toward achieving large-scale production of high quality cells in a reproducible, controllable, scalable, and cost-effective manner. Planar systems, such as multi-layered plates, have been commonly used to produce anchorage-dependent hMSCs for early-stage clinical trials, and scale-up of such platforms may be adequate to manufacture some hMSC products for autologous treatments and rare allogeneic therapies with a small number of patients requiring small-size of batch lots. However, to target many patients, these technologies would be inadequate to meet commercial scale manufacturing for allogeneic hMSC therapies, which demand a large batch size (i.e., over 1012 cells per batch) to realize wide implementation of the therapies at reasonable costs. To overcome this manufacturing barrier, efforts are being made to develop a novel bioreactor platform that is scalable and speedy while enabling high volumetric manufacturing of quality-assured cells. In this chapter, we review hMSC manufacturing challenges for large-scale allogeneic products, specifically focusing on the upstream process.