The therapeutic efficacy of Mesenchymal Stromal Cells (MSCs) has been demonstrated in a multitude of pre-clinical studies and clinical trials, yet the translation of MSC therapies is limited by biological factors such as inter- and intra-donor variability in the function, differentiation capacity and proliferation rate of MSCs, as well as extrinsic factors such as the implementation of standardised reporting and characterisation guidelines. The complex relationship between MSC heterogeneity and recipient heterogeneity further contributes to the challenging interpretation of results and complicates the comparison of outcomes between studies. Efforts to enhance the therapeutic efficacy of MSCs have been made, however only a few focus on addressing heterogeneity. Aside from this, a clear understanding of the mechanism of action of MSCs and the development of appropriate functional/potency assays could aid in the standardisation of MSC therapies and provide information for the stratification of recipients. This review discusses the challenges associated with the clinical translation of MSCs and critically evaluates recent advancements in the strategies to enhance the therapeutic efficacy of MSCs.
Etzenberger et al. (2026) studied this question.