First Clinical Experiences Using Preconditioning Approaches to Improve MSC-Based Therapies

Describe the rationale for preconditioning MSCs prior to use as therapy and the state-of-the-art of using preconditioning of MSCs in clinical settings.

Mounting preclinical data supports preconditioning of mesenchymal stromal cells (MSCs) to enhance their therapeutic efficacy. Most research has focused on cytokine priming and hypoxic preconditioning, while other approaches, such as glycoengineering, remain relatively understudied. Despite strong preclinical data, clinical evidence supporting preconditioning strategies are limited to six Phase I clinical trials (most of them in progress).

Here, we succinctly discuss the rationale for preconditioning using cytokines, hypoxia, and glycoengineering, while elaborating on the respective clinical experiences. Overall, we note that preconditioning is highly dependent on the desired application, and therefore requires elucidating the mechanism of action of the MSCs used for therapy. Preconditioning may also help mitigate heterogeneity of MSC lots. Based on the remarkable safety profile of MSCs, even when used in allogeneic settings, the role of preconditioning prior to their final formulation might be the key to reach expected therapeutic outcomes.