Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

Abstract

Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

How the Pathological Microenvironment Affects the Behavior of Mesenchymal Stem Cells in the Idiopathic Pulmonary Fibrosis

“…In the last few years, many studies tried to clarify the role of MSCs in inflammatory processes. It has been seen that MSCs can modulate the cells of the innate and adaptive immune system by secreting cytokines [33]. In this scenario, the expression and secretion of selected inflammatory cytokines such as IL1A, IL1B, IL4, IL6, IL8, IL12, TNF-α, and G-CSF were analyzed in C-MSCs, IPF-MSCs, and NHLF before and after co-cultures.…”

The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration

“…MSCs spontaneously differentiate into chondrocytes and osteocytes and, at the same time, are able to suppress pathogenic immune response in inflamed synovial tissue . Therefore, during the last decade, therapeutic potential of MSCs in cell‐based therapy of RA and OA have been intensively explored in animal and clinical trials . Several lines of evidence suggested crucially important role of MSC‐derived IL‐1Ra for chondrogenic and osteogenic potential of MSCs and for MSC‐based alleviation of joint inflammation …”

“…71 Therefore, during the last decade, therapeutic potential of MSCs in cell-based therapy of RA and OA have been intensively explored in animal and clinical trials. 72,73 Several lines of evidence suggested crucially important role of MSC-derived IL-1Ra for chondrogenic and osteogenic potential of MSCs and for MSC-based alleviation of joint inflammation. 69,74,75 Lee and coworkers demonstrated that MSCs (5 × 10 6 cells, intraperitoneally injected on Days 0 and 43) significantly alleviated synovial inflammation and cartilage destruction in IL-1RaKO mice.…”

HIF1α‐dependent metabolic reprogramming governs mesenchymal stem/stromal cell immunoregulatory functions

“…The more recent but not the least documented anti‐inflammatory and immunoregulatory functions of MSC represent a huge interest in clinic for the treatment of inflammatory and autoimmune diseases 1,4,5 . Indeed, MSC have been described to repress the function of most, if not all, pro‐inflammatory immune cells including Th1 and Th17 lymphocytes while inducing the generation of regulatory T cells in vitro and in vivo (for review see 6). Although considered as candidate of choice for diverse therapeutic applications, MSC are highly plastic and consequently, their phenotype and functions are molded by factors present in their microenvironment including the pro‐inflammatory cytokines tumor necrosis factor α (TNFα) and Interferon gamma γ (IFNγ).…”