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Review
. 2022 Sep 23:13:1010399.
doi: 10.3389/fimmu.2022.1010399. eCollection 2022.

Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

Madina Sarsenova  1 , Yevgeniy Kim  1 , Kamila Raziyeva  1 , Bexultan Kazybay  1 , Vyacheslav Ogay  2 , Arman Saparov  1
Affiliations
Review

Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

Madina Sarsenova et al. Front Immunol. .

Abstract

Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well as their ability to improve tissue regeneration, these cells have attracted the attention of scientists and clinicians for the treatment of different inflammatory and immune system mediated disorders. However, various clinical trials using MSCs for the therapeutic purpose are conflicting and differ from the results of promising preclinical studies. This inconsistency is caused by several factors such as poor migration and homing capacities, low survival rate, low level of proliferation and differentiation, and donor-dependent variation of the cells. Enhancement and retention of persistent therapeutic effects of the cells remain a challenge to overcome in MSC-based therapy. In this review, we summarized various approaches to enhance the clinical outcomes of MSC-based therapy as well as revised current and future perspectives for the creation of cellular products with improved potential for diverse clinical applications.

Keywords: 3D culturing; cell therapy; cytokines; genetic modifications; hypoxia; immunomodulation; mesenchymal stem cells; preconditioning.

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Conflict of interest statement

The 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
Immunomodulatory properties of MSCs. MSCs are capable of regulating the function of various cells of the immune system. Thus, MSCs stimulate macrophage polarization from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype and regulate DC differentiation toward the tolerogenic phenotype. Also, MSCs suppress mast cell degranulation and downregulate the production of IL-6, MIP-2, Bcl-xl and Mcl-1 by neutrophils and expression of CD244 and NKG2D by NK cells. Moreover, MSCs switch the phenotype of B and T cells toward Bregs and Tregs, respectively.
Figure 2
Figure 2
Different strategies for the enhancement of MSC therapeutic properties. Various approaches were used to enhance the immunomodulatory potential of MSCs including cytokines and factors, immune receptor agonists, culture condition modification, hypoxia, autophagy, genetic modification, and other agents. The proposed strategies lead to an increase in the survival, proliferative, secretory, homing, migratory, and differentiation capacities of MSCs, which results in the improvement of their therapeutic effects.
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