Mesenchymal Stromal Cell-Based Therapy: New Perspectives and Challenges

Abstract

Stem cells have been the focus of intense research opening up new possibilities for the treatment of various diseases. Mesenchymal stromal cells (MSCs) are multipotent cells with relevant immunomodulatory properties and are thus considered as a promising new strategy for immune disease management. To enhance their efficiency, several issues related to both MSC biology and functions are needed to be identified and, most importantly, well clarified. The sources from which MSCs are isolated are diverse and might affect their properties. Both clinicians and scientists need to handle a phenotypic-characterized population of MSCs, particularly regarding their immunological profile. Moreover, it is now recognized that the tissue-reparative effects of MSCs are based on their immunomodulatory functions that are activated following a priming/licensing step. Thus, finding the best ways to pre-conditionate MSCs before their injection will strengthen their activity potential. Finally, soluble elements derived from MSC-secretome, including extracellular vesicles (EVs), have been proposed as a cell-free alternative tool for therapeutic medicine. Collectively, these features have to be considered and developed to ensure the efficiency and safety of MSC-based therapy. By participating to this Special Issue “Mesenchymal Stem/Stromal Cells in Immunity and Disease”, your valuable contribution will certainly enrich the content and discussion related to the thematic of MSCs.

HCMV Infection in a Mesenchymal Stem Cell Niche: Differential Impact on the Development of NK Cells versus ILC3

“…Although it is currently not known at which developmental stage and at which site they are initially generated, it is common believe that NKG2C + adaptive NK cells are terminally differentiated cells originating from already mature CD56 dim NK cells, which are mostly located in the circulation. Thus, the MSC-based niche would preferentially support development of NK cells up to the stage of mature NK cells but would not support or might even suppress the generation of terminally differentiated NKG2C + NK cells given the powerful immunoregulatory properties of MSC towards effector T and NK cells [33].…”

“…In this context, we have recently established BM-derived MSCs as a novel human stem cell niche that efficiently and robustly support NK cell development from cord blood (CB)-derived HSPC [31]. It should be stressed that MSCs play a dual role in this context, since on the one hand they are well described to suppress NK and T cell effector functions [32] and are clinically employed as immunoregulatory cellular therapeutics [33], but on the other hand are supporting hematopoietic development in the bone marrow stem cell niche [3].…”

Potential roles of extracellular vesicles in the pathophysiology, diagnosis, and treatment of autoimmune diseases

“…EVs act an important role in the therapeutic effect of MSCs and are therefore considered as a potential alternative to MSCs. Thus, MSC-derived EVs (MSC-EVs) would induce a regulatory response in the function of T-, B-, and monocyte-derived dendritic cells [56]. In the present work, MSC-EVs have been shown to possess immunomodulatory functions which promote B cell activation, induction of Breg and B cell proliferation was compared to that the whole MSCs [57].…”

Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells

“…Indeed, several studies indicate that MSCs need to be licensed by inflammatory stimuli, such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-1 α/β, to exert or improve their immunosuppressive actions [14]. Thus, in recent years, several studies have evaluated whether preconditioning bone marrow-derived MSCs cultured in vitro with IFN-γ and TNF-α could elicit a stronger immunosuppressive activity [4,[15][16][17]. IFN-γ induces a transient expression of indoleamine-2,3 dioxygenase (IDO) which inhibits T cell activation, proliferation, and functionality due to L-tryptophane depletion [9].…”