AUTHOR=Fernández-Santos Maria Eugenia , Garcia-Arranz Mariano , Andreu Enrique J. , García-Hernández Ana Maria , López-Parra Miriam , Villarón Eva , Sepúlveda Pilar , Fernández-Avilés Francisco , García-Olmo Damian , Prosper Felipe , Sánchez-Guijo Fermin , Moraleda Jose M. , Zapata Agustin G. 

TITLE=Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.918565

DOI=10.3389/fimmu.2022.918565

ISSN=1664-3224

ABSTRACT=In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning of cytokine production, cell homing and immunomodulatory properties, have been developed. These ex vivo cell manipulations give rise to a new generation of MSCs 2.0 that needs to be validated and explored in a clinical setting. Along with other related products with promising therapeutic potential, such as small extracellular vesicles (i.e., exosomes), a special form of MSC modifications that also needs extensive consideration, MSCs products are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. Nevertheless, the manufacture and handling of these cells for their use as advanced therapy medicine products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.