Key mediators of the efficacy of mesenchymal stem cells on in vivo disease models

Abstract

Mesenchymal stem cells (MSCs) are considered to be effective treatments for various diseases, and a wide variety of clinical studies have been performed worldwide. However, substantial obstacles remain before they can be approved and disseminated as treatments. A major bottleneck is the elucidation of their mechanisms of action, and the molecules that are essential for their efficacy have not been fully characterized. In this paper, I review the studies that attempted to identify the key mediators of MSCs that are involved in their effects on disease using in vivo models. More specifically, studies are discussed in which reductions in the efficacy of MSCs in animal models of disease were induced by the absence of key mediators. The target diseases were lung, joint, cerebral nerve, or cardiac diseases and graft-versus-host disease (GVHD). The following molecules were identified and are discussed herein: TSG-6, VEGF, KGF, HGF, claudin-4, ANXA1, MANF, PYCR1, integrin β1, PDGFRβ, type-II collagen, CD151, TIMP3, TGF-β1, BDNF, COX-2, Botch, IL-1β, CTRP3, CXCR4, miR-34c, FSTL1, IDO, iNOS, IFNγR1, PGES, Chi3l1, and IL-6. These are key mediators of the efficacy of MSCs in vivo.

Keywords: cell therapy product; in vivo; mechanism of action; mesenchymal stem cells.

Graphical Abstract

Graphical abstract was created in BioRender. Nakamura, K. (2025) https://BioRender.com/u98s099

Figure 1.

Number of clinical studies of mesenchymal stem cells and classification of target diseases (total n = 1694). ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; GVHD: graft-versus-host disease; MSC: mesenchymal stem cell.