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Review
. 2022 Jun 9:13:918565.
doi: 10.3389/fimmu.2022.918565. eCollection 2022.

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

Maria Eugenia Fernández-Santos  1   2 , Mariano Garcia-Arranz  3   2 , Enrique J Andreu  4   2 , Ana Maria García-Hernández  5   2 , Miriam López-Parra  6   2 , Eva Villarón  6   2 , Pilar Sepúlveda  7   2 , Francisco Fernández-Avilés  1   2 , Damian García-Olmo  3   2 , Felipe Prosper  4   2 , Fermin Sánchez-Guijo  6   2 , Jose M Moraleda  5   2 , Agustin G Zapata  8   2
Affiliations
Review

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

Maria Eugenia Fernández-Santos et al. Front Immunol. .

Abstract

MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal 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.

Keywords: ATMPs; GMP manufacturing; MSCs; extracellular vesicles; legal requirements.

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Conflict of interest statement

FS-G has received honoraria and/or research support from Novartis, Kite/Gilead, Celgene/BMS, Pfizer, Takeda and Roche. DG-O is a member of the Advisory Board of Tigenix SAU and received fees from Takeda. ML-P has received honoraria from Novartis, Kite/Gilead and Celgene/BMS. JM has received research support from Roche, Pfizer, Jazz Pharma, Sandoz-Novartis, Gilead, Celgene, and Takeda not related to this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of key aspects on Mesenchymal Stromal Cells (MSCs) isolation and expansion. (A) MSC Source Selection; (B) Tissue/Cell Collection; (C) MSCs Isolation and Expansion.
Figure 2
Figure 2
Critical Steps in MSC Manifacturing. (MSCs, Mesenchymal Stromal Cells; DMSO, Dimethyl sulfoxide).
See this image and copyright information in PMC

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