Controversies regarding transplantation of mesenchymal stem cells

Table 1 The most common immunological mechanisms employed by mesenchymal stem cells

Properties	Mechanisms	Ref.
Suppression of T-cell proliferation	MSCs are adept at inhibiting the proliferation and activation of T lymphocytes, a vital component of the adaptive immune response. This effect is mediated by releasing soluble factors such as IDO and PGE2, which create an immunosuppressive microenvironment	[15,16]
Induction of Tregs	MSCs promote the generation and expansion of regulatory T cells, or Tregs, which play a crucial role in immune tolerance and suppressing excessive immune reactions. This induction of Tregs is partly attributed to interactions between PD-L1 on MSCs and PD-1 on T cells	[17-19]
Modulation of DCs	MSCs influence the maturation and function of DCs, pivotal antigen-presenting cells in the immune system. They inhibit the expression of co-stimulatory molecules on DCs and reduce their ability to activate T cells, thereby tempering immune responses	[20]
Reduction of inflammatory cytokines	MSCs secrete anti-inflammatory cytokines like IL-10, TGF-β, and HGF, while simultaneously dampening the production of pro-inflammatory cytokines, including IFN-γ	[21,22]
Promotion of macrophage polarization	MSCs can skew macrophages towards an anti-inflammatory, tissue-healing M2 phenotype, fostering a regenerative environment and mitigating tissue damage	[23]
Immune cell anergy	MSCs can induce a state of anergy in T cells, rendering them functionally inactive and refractory to activation signals. This effect is conducive to immune tolerance and reduced autoimmune responses	[24]
Exosome-mediated communication	MSCs release immunomodulatory exosomes that carry bioactive molecules, including microRNAs and proteins, capable of regulating immune cell behavior and suppressing inflammation	[25]

Tregs: Regulatory T cells; IDO: Indoleamine 2,3-dioxygenase; PGE2: Prostaglandin E2; PD-L1: Programmed death-ligand 1; PD-1: Programmed cell death protein 1; DCs: Dendritic cells; MSCs: Mesenchymal stem cells; IL-10: Interleukin-10; TGF-β: Transforming growth factor-beta; HGF: Hepatocyte growth factor; IFN-γ: Interferon-gamma.