Interplay between mesenchymal stromal cells and immune system: clinical applications in immune-related diseases

Abstract

Mesenchymal stromal cells (MSCs) are a mesodermal stem cell population, with known self-renewal and multilineage differentiation properties. In the last century, MSCs have been widely used in regenerative medicine and tissue engineering approaches. MSCs initially were isolated from bone marrow aspirates, but currently have been identified in a great number of tissues of the human body. Besides their utilization in regenerative medicine, MSCs possess significant immunoregulatory/immunosuppressive properties, through interaction with the cells of innate and adaptive immunity. MSCs can exert their immunomodulatory properties with either cell-cell contact or via paracrine secretion of molecules, such as cytokines, growth factors and chemokines. Of particular importance, the MSCs’ immunomodulatory properties are explored as promising therapeutic strategies in immune-related disorders, such as autoimmune diseases, graft versus host disease, cancer. MSCs may also have an additional impact on coronavirus disease-19 (COVID-19), by attenuating the severe symptoms of this disorder. Nowadays, a great number of clinical trials, of MSC-mediated therapies are evaluated for their therapeutic potential. In this review, the current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation were highlighted. Also, the most important aspects, regarding their potential application in immune-related diseases, will be highlighted. The broad application of MSCs has emerged their role as key immunomodulatory players, therefore their utilization in many disease situations is full of possibilities for future clinical treatment.

Mesenchymal stromal cell delivery as a potential therapeutic strategy against COVID-19: Promising evidence from in vitro results

“…Initially, the characterization of the thawed WJ and BM-MSCs was performed, and no discrepancies were observed according to the already published literature[ 22 - 24 ]. Both thawed WJ and BM-MSCs fulfilled the criteria outlined by the ISCT and hence were considered as well-defined cells[ 23 , 24 ].…”

“…WJ-MSCs possess more naïve cells compared to MSCs derived from adult sources. Moreover, it has been shown that MSCs derived from fetal tissues are characterized by fewer mutations and epigenetic modifications, greater proliferation, and differentiation capacity, compared to adult MSCs[ 22 ] In addition, MSCs from fetal tissues can be isolated noninvasively (compared to adult MSCs)[ 22 ]. Allogeneic MSCs are considered immune-evasive cells, as they are not expressing either the HLA-DR or stimulatory (CD40) and co-stimulatory molecules (CD80 and CD86)[ 22 , 26 ].…”

“…MSCs represent a mesodermal multipotent stem cell population, which initially was discovered in bone marrow (BM) aspirate samples by Bianco et al [ 21 ]. Currently, MSCs can be obtained from various sources of the human body, including the liver, lungs, adipose tissue (AT), umbilical cord blood, placenta, and umbilical cord tissue (Wharton’s Jelly [WJ] tissue)[ 22 ]. Based on the proposed guidelines of the MSC Committee of the International Society for Cell and Gene Therapy (ISCT), MSCs must fulfill specific criteria[ 23 , 24 ].…”

“…Besides, according to the proposed guidelines by the ISCT, MSCs from different sources are characterized by variable functional properties. Indeed, fetal MSCs ( e.g., derived from amniotic fluid, placenta, and WJ tissue) may have significant differences in terms of proliferation and differentiation efficiency, telomere length, and telomerase activity, compared to adult MSCs ( e.g., adipose tissue and bone marrow)[ 22 , 27 - 29 ]. Also, it has been shown that fetal MSCs are characterized by better immunoregulatory/immunosuppressive properties and have acquired less mutagenic or epigenetic changes to their genome, in comparison to MSCs derived from adult sources[ 22 , 27 - 29 ].…”

Characterization of an Innovative Biomaterial Derived From Human Wharton’s Jelly as a New Promising Coating for Tissue Engineering Applications

“…WJ was also used in this study for its important content of MSC, immune evasive cells showing an important potential for tissue engineering applications with interesting immunomodulation properties ( Weiss et al, 2008 ; El Omar et al, 2014 ; Li and Hua, 2017 ; Mallis et al, 2021 ). WJ-MSC were mechanically collected by applying the explant method based on the ability of cells to migrate out of the tissue and adhere to the culture surface.…”