Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Treatment of Viral Diseases

Abstract

Mesenchymal stem cells (MSCs) are adult, immunomodulatory stem cells which reside in almost all postnatal tissues. Viral antigens and damage-associated molecular patterns released from injured and infected cells activate MSCs, which elicit strong antiviral immune response. MSC-sourced interferons and inflammatory cytokines modulate the cytotoxicity of NK cells and CTLs, enhance the antigen-presentation properties of DCs and macrophages, regulate cytokine synthesis in CD4+ T helper cells and promote antibody production in B cells. After the elimination of viral pathogens, MSCs produce immunoregulatory cytokines and trophic factors, prevent the over-activation of immune cells and promote tissue repair and regeneration. In this review article, we summarize the current knowledge on the molecular mechanisms that are responsible for the MSC-dependent elimination of virus-infected cells, and we emphasize the therapeutic potential of MSCs and their secretomes in the treatment of viral diseases.

Secretory Profile of Adipose-Tissue-Derived Mesenchymal Stem Cells from Cats with Calicivirus-Positive Severe Chronic Gingivostomatitis

“…These changes observed in the secretion of factors towards a pro-inflammatory profile in the fAd-MSCs of FCV-positive FCGS patients are similar to those observed in MSCs from other species when suffering viral infections [25,33] or after experimental transfection with the virus in disease models [34]. It is, however, important to keep the limitations of the multiplex assay in mind regarding its sensitivity; other analytes might have remained undetected, as has happened in other studies on feline patients using this technique [27].…”

Revisiting the role of mesenchymal stem cells in tuberculosis and other infectious diseases

“…The crosstalk between MSCs and various immune cells depends on the environment and pathological or physiological conditions in which they are present, such as repair, regeneration, transplantation, or infection. MSCs secrete proangiogenic components during tissue rejuvenation, stimulating neovascularization through juxtracrine and paracrine signaling [ 90 ]. In vivo and in vitro experiments have demonstrated the suppressive behavior of immune cells in response to MSCs.…”

Mesenchymal stem cells-based therapy in liver diseases

“…The immunosuppressive activity of MSCs has raised safety concerns regarding primary viral infections and increased risk of viral reactivation. However, MSCs can promote the proliferation of virus-specific immune cells and their antiviral exertion [ 20 , 21 ]. For example, using the SIV model of AIDS, some researchers have recently found that MSCs can restore antiviral immunity by reconstituting damaged lymphoid follicles, as evidenced by robust regeneration of germinal centers, as well as restoration of follicular B cells and Tfh cells leading to increased levels of anti-SIV antibodies and SIV-specific CD8 + T cells, resulting in viral reduction [ 539 ].…”

“…In immunocompromised liver diseases, such as chronic viral hepatitis (CVH) and HCC, this property of MSCs may help viruses and tumors to evade immune surveillance, and thus their therapeutic value has been somewhat overshadowed [ 18 – 20 ]. In fact, MSCs can not only interact with liver immune cells to act as direct immune enhancers, but can also be engineered to act as cellular carriers for antiviral and antitumor vaccines and carry oncolytic viruses and other types of immunomodulators to indirectly modulate the liver immune microenvironment for antiviral and antitumor purposes [ 21 , 22 ]. Taking advantage of the tumor tropism and intra-tumor penetration properties of MSCs, they have been used as cellular vectors to load antitumor-related drugs to precisely target tumor tissues and then modulate the tumor microenvironment (TME) and kill tumor cells to achieve synergistic antitumor effects [ 22 ].…”