ABSTRACT
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.
