Mesenchymal Stromal Cells: From Discovery to Manufacturing and Commercialization

Abstract

Over the last decades, mesenchymal stromal cells (MSC) have been the focus of intense research by academia and industry due to their unique features. MSC can be easily isolated and expanded through in vitro culture by taking full advantage of their self-renewing capacity. In addition, MSC exert immunomodulatory effects and can be differentiated into various lineages, which makes them highly attractive for clinical applications in cell-based therapies. In this review, we attempt to provide a brief historical overview of MSC discovery, characterization, and the first clinical studies conducted. The current MSC manufacturing platforms are reviewed with special attention regarding the use of bioreactors for the production of GMP-compliant clinically relevant cell numbers. The first commercial MSC-based products are also addressed, as well as the remaining challenges to the widespread use of MSC-derived products.

Scalable Manufacturing of Human Mesenchymal Stromal Cells in the Vertical‐Wheel Bioreactor System: An Experimental and Economic Approach

“…The costs of goods per dose obtained within the scope of this study ($11 000–$21 000) are within the range of costs of goods obtained in other MSC bioprocess modeling studies . Given that the final prices of commercially available ATMPs are in the range of $500–$850 000 per dose, interventions aimed at reducing the costs of goods per dose are key to ensure sustainability of cell based products under reimbursement constraints …”

“…The costs of goods per dose obtained within the scope of this study ($11 000-$21 000) are within the range of costs of goods obtained in other MSC bioprocess modeling studies. [20,40,41] Given that the final prices of commercially available ATMPs are in the range of $500-$850 000 per dose, [20,42,43] interventions aimed at reducing the costs of goods per dose are key to ensure sustainability of cell based products under reimbursement constraints. [42] The higher cell seeding density requirements of microcarrier-based technologies is a consequence of the suboptimal MSC adhesion rates in microcarriers and impacts the process operation.…”

Scalable Production and Isolation of Extracellular Vesicles: Available Sources and Lessons from Current Industrial Bioprocesses

“…Different bioreactor systems have been tested to scale up the EV production, directly transferring the advancements developed in the field of stem cell expansion . The simplest scale‐up approach relies on the substitution of single‐layer T‐flasks with multilayered cell culture flasks to provide a larger surface area for cell expansion.…”

“…In this setup, cells are cultivated on microcarriers, typically of spherical shape, which provide a high surface area to volume ratio for cell growth . Impellers are used to enhance mixing and maintain homogeneous culture conditions that can be easily monitored and controlled . This configuration led to a 140‐fold increase in the produced EVs …”

Improving treatment outcomes for MDR-TB — Novel host-directed therapies and personalised medicine of the future

“…Mesenchymal stromal cells (MSC), known for their antiinflammatory, immunomodulatory properties and safety in several clinical modalities (Mizukami and Swiech, 2018), are excellent candidates for treating patients with MDR-TB. Adjunctive therapy with a single infusion of bone marrow-derived autologous MSC has been clinically evaluated in two separate studies involving patients with MDR/XDR-TB.…”