Clinical Manufacturing of Human Mesenchymal Stromal Cells using a Potency-Driven Paradigm

Purpose of Review In this review, we discuss the current state of scalable manufacturing of a reproducible and potent allogeneic MSC product. Recent Findings Progress in the manufacturing of MSCs is focused on automated systems such as hollow-fiber and microcarrier-based bioreactor designs as viable paths towards commercial scales. Insights highlighted from scaled-down bioprocess screenings that have helped bridge the transition to scale-up manufacturing are discussed. The quality of MSCs, specifically potency assay development, is considered to systematically drive bioprocess decision making during scale-up. These potency assays include MSC activation or T cell suppression assays to understand the immunomodulatory properties of MSCs as referenced to surrogate biomarkers of inflammatory cytokines that activate MSCs and their biological functions in vitro. Reverse engineering potency based on clinical data is emphasized to develop accurate assays that predict in vivo potency. Summary Ultimately, these considerations will help new and existing developers better standardize operating procedures that will influence the scalable production of a potent MSC therapy.