Abstract

The potential of mesenchymal stem cells (MSCs) in regenerative medicine has been largely known due to their capability to induce tissue regeneration in vivo with minimum inflammation during implantation. This adult stem cell type exhibit unique features of tissue repair mechanism and immune modulation mediated by their secreted factors, called secretome. Recently, the utilization of secretome as a therapeutic agent provided new insight into cell-free therapy. Nevertheless, a sufficient amount of secretome is necessary to realize their applications for translational medicine which required a proper biomanufacturing process. Several factors related to their production need to be considered to produce a clinical-grade secretome as a biological therapeutic agent. This viewpoint highlights the current challenges and considerations during the biomanufacturing process of MSCs secretome.

Highlights

  • EGF: GM-CSF: M-CSF: PGE2: miR-21: miR-210: IDO: CXCL5: Epidermal growth factor granulocyte/monocyte growth factor Macrophage colony stimulating factor Prostalglandin E2 microRNA-21 microRNA-210 Indoleamine 2,3-dioxygenase C-X-C Motif Chemokine Ligand 5

  • The capability of mesenchymal stem cells (MSCs) to differentiate into multiple lineages with less immune rejection makes them become a good candidate for cell-based regenerative therapy

  • Aside from their applications in cell-based therapy, the study of MSCs secretome as a cell-free therapeutic agent was increased significantly

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Summary

Brief Introduction

The capability of mesenchymal stem cells (MSCs) to differentiate into multiple lineages with less immune rejection makes them become a good candidate for cell-based regenerative therapy. To the best of our knowledge, most of the current studies are concentrated on nucleic acid, peptide, growth factors/ hormone/cytokine, enzymes, extracellular matrix, and Lipid components (Table 1) These compounds have been known to contribute to some therapeutic potential, which can be produced by in vitro MSCs culture for possible translational medicine. One of the potential biomanufacturing approaches to improving the quality and cost-effectiveness is by using dialysis culture technologies, such as hollow fiber (Barckhausen et al, 2016) or simple dialysis culture by modified culture insert with 4–12 kDa molecular weight cutoff dialysis membrane on the bottom side (Torizal et al, 2021) This culture system enables the localization and accumulation of high molecular weight secretome components, such as the one that enveloped by extracellular vesicle or as complex soluble proteins while continuously refining the small molecule nutrition in the basal media by continuous removal of waste metabolic byproducts, such as lactate and NH3 (Fig. 2), and supplying the nutrition from the culture medium (Torizal et al, 2021). Several examples of MSCs secretome components and their possible therapeutic potential

Promoting inflammatory response against infection
Conclusion and Future Perspectives
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