Sufficient numbers of multipotent Mesenchymal Stromal Cells is a great challenge that the industry must address to meet the increasing demand for clinical size product batches. This can be understood as an opportunity to exploit existing bioprocessing technologies already tested successfully in the production of vaccines and biologicals. Herein we analyse the transition from traditional manual cell expansion 2D methodologies to scalable and automated platforms with the capacity to yield billions of cells per batch in a robust, reproducible and cost-effective manner in compliance with current Good Manufacturing Practices. This review gives special relevance to the key features of multiple manufacturing platforms, particularly those using microcarriers to support cell expansion and single-use bioreactors.