Identification and Evaluation of New Immunoregulatory Genes in Mesenchymal Stromal Cells of Different Origins: Comparison of Normal and Inflammatory Conditions

Abstract

BackgroundMesenchymal stromal cells (MSCs) possess potent immunomodulatory properties that increase their value as a cell-based therapeutic tool for managing various immune-based disorders. Over the past years, accumulated results from trials using MSCs-based therapy have shown substantial contradictions. Although the reasons underlying these discrepancies are still not completely understood, it is well known that the immunomodulatory activities mediated by distinct MSCs differ in a manner dependent on their tissue origin and adequate response to inflammation priming. Thus, characterization of new molecular pathway(s) through which distinct MSC populations can exert their immunomodulatory effects, particularly during inflammation, will undoubtedly enhance their therapeutic potential.Material/MethodsAfter confirming their compliance with ISCT criteria, quantitative real time-PCR (qRT-PCR) was used to screen new immunoregulatory genes in MSCs, derived from adipose tissue, foreskin, Wharton’s jelly or the bone-marrow, after being cultivated under normal and inflammatory conditions.ResultsFGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals.ConclusionsOur observations suggest that these identified immunoregulatory genes may be considered as potential candidates to be targeted in order to enhance the immunomodulatory properties of MSCs towards more efficient clinical use.

Identification of Differentially Expressed lncRNAs and mRNAs in Children with Acquired Aplastic Anemia by RNA Sequencing

“…Our work showed that these downregulated DEmRNAs can be regulated by lncRNAs AC147651.1 and AC111000.4 in cis-and transregulation manners. Hence, we can conclude that lncRNAs What is more, IDO1 [28] and SEMA7A [29] were reported to be important in the immunomodulatory effect of mesenchymal stromal cells in acquired AA. In our study, IDO1 and SEMA7A were downregulated and they were shown to be cis-and trans-regulated by lncRNAs AC007991.2 and RHOXF1P1.…”

Toll-Like Receptor 3 Activator Preconditioning Enhances Modulatory Function of Adipose‑Derived Mesenchymal Stem Cells in a Fully MHC-Mismatched Murine Model of Heterotopic Heart Transplantation

“…FGL2 is primarily bound to FcgR, including FcgRIIB and FcgRIII [44]. By a previous report, FGL2 mRNA expression was upregulated in human ADSCs with a cocktail of pro-inflammatory cytokines, specifically IL-1b, TNF-a, IFN-a, and IFN-g [45]. FGL2was reported as a novel effector molecule in the immunoregulation of Treg cells [46].…”

Aldehyde dehydrogenase activity of Wharton jelly mesenchymal stromal cells: isolation and characterization

“…Their self-renewal, multilineage differentiation capacity and immunomodulatory abilities make mesenchymal stromal cells (MSCs) promising tools for different therapeutic applications. According to their origin, MSCs may share some characteristics (Hoogduijn et al 2010) but may also present functional differences related to distinct gene and protein profiles (Busser et al 2015;Fayyad-Kazan et al 2017). The umbilical cord is becoming an important alternative source of MSCs (Davies et al 2017).…”