This month we published two papaers on the challenges of using mesenchymal stromal cells (MSCs) in cell therapy applications. We looked at the recent literature on use of MSCs in regenerative medicine, a multi-disciplinary field in which cells, tissues and/or gene sequences are used to repair or replace damaged tissues or to treat disease. Almost 20 years after the term “mesenchymal stem cell” was coined, there is still much confusion regarding use of the term “stem” as opposed to the, perhaps more broadly correct “stromal”. In [Regen Med 2019] we asked “does this matter?” especially given the broad range of applications for MSCs which appear unrelated to stemness and differentiation potential. Highlighting the inherent variability of MSC populations, we considered population identity and mechanisms of action as key criteria for regulatory approvals. We developed further the theme of heterogeneity in our second paper [Frontiers in Immunology 2019], emphasising that variation within and between populations is a biological inevitability that must be recognised and addressed more systematically in the development of MSC-based regenerative medicine products.