Quantifiable Metrics for Predicting MSC Therapeutic Efficacy

Currently there are over 600 clinical trials listed at www. clinicaltrials.gov utilizing Mesenchymal Stromal Cells (MSCs) as an experimental cell-based therapy, making MSCs the most commonly employed cell type under investigation for treating human diseases. MSCs have gained widespread use in regenerative medicine due to their demonstrated potency in a broad range of experimental animal models of disease and their excellent safety profile in human clinical trials. However, while MSC-based therapies have clearly shown benefits in patients with ischemic and immune-related disorders, many trials completed to date have yielded suboptimal outcomes and several have failed to meet their primary endpoints of efficacy. A challenge in the development of efficacious MSC-based therapies is the inability to consistently manufacture homogeneous populations of cells with known efficacy for a specific disease indication that yield predictable and reproducible patient outcomes. This difficulty stems from the fact that methods routinely used to isolate MSCs [1–4] yield populations that exhibit significant heterogeneity in terms of morphologic features, growth rate, life span, differentiation potential, and potency in functional-based assays [5–8]. Donor-to-donor heterogeneity coupled with the lack of standardized manufacturing protocols makes it impossible to determine if patients enrolled in different clinical trials received functionally equivalent MSC preparations. The lack of metrics that discriminate functional differences between populations further confounds efforts to select the most suitable populations for a given disease indication. Therefore, the identification and reduction to practice of manufacturing schemes with deployable metrics to assess efficacy prior to patient administration is necessary to improve clinical outcomes and advance MSCbased therapies beyond the experimental phase.