Interactions Between Mesenchymal Stem Cells and Dendritic Cells
Department of Experimental Medicine, University of Genoa, Via L.B. Alberti 2, Genoa, 16132 , Italy, .Advances in biochemical engineering/biotechnology (Impact Factor: 1.66). 08/2012; 130. DOI: 10.1007/10_2012_154
Mesenchymal stem or stromal cells (MSC) are considered a promising new therapeutic strategy for the treatment of several pathological conditions. Due to their immunomodulatory properties, they are currently employed in clinical trials aimed at preventing or treating steroid-resistant acute graft-versus-host disease (GvHD), a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT). In addition, the use of MSC has been proposed for the treatment of autoimmune diseases. A number of recent studies have focused on the influence of MSC on dendritic cell (DC) function. DCs play a critical role in initiating and regulating immune responses by promoting antigen-specific T cell activation. Moreover, they are involved in efficient cross-talk with different cells of the innate immune system. DC are the most effective antigen-presenting cells and prime naïve T cells to initiate adaptive immune responses including those against allogeneic cells or self-antigens. Thus, alteration of DC generation or function may greatly contribute to the inhibition of T cell responses. In this context, MSC were shown to interfere with DC maturation from monocytes or CD34+ hemopoietic precursors thus further confirming their role in immune regulation and their usefulness in cell-based therapies.
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- "As reviewed by Spaggiari et al., most studies that address the interaction between MSCs and APCs have demonstrated that MSCs modulate dendritic cells (DCs) at multiple levels. Overall, MSCs alter the phenotype, cytokine release, differentiation and maturation of DCs and compromise their antigen presentation ability . Recently, a study investigated the influence of MSCs on different monocyte subpopulations (classical, intermediate and nonclassical ) . "
ABSTRACT: Because of their well-recognized immunomodulatory properties, mesenchymal stromal cells (MSCs) represent an attractive cell population for therapeutic purposes. In particular, there is growing interest in the use of MSCs as cellular immunotherapeutics for tolerance induction in allogeneic transplantations and the treatment of autoimmune diseases. However, multiple mechanisms have been identified to mediate the immunomodulatory effects of MSCs, sometimes with several ambiguities and inconsistencies. Although published studies have mainly reported the role of soluble factors, we believe that a sizeable cellular component plays a critical role in MSC immunomodulation. We refer to these cells as regulatory immune cells, which are generated from both the innate and adaptive responses after co-culture with MSCs. In this review, we discuss the nature and role of these immune regulatory cells as well as the role of different mediators, and, in particular, regulatory immune cell induction by MSCs through interleukin-10. Once induced, immune regulatory cells accumulate and converge their regulatory pathways to create a tolerogenic environment conducive for immunomodulation. Thus, a better understanding of these regulatory immune cells, in terms of how they can be optimally manipulated and induced, would be suitable for improving MSC-based immunomodulatory therapeutic strategies.
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ABSTRACT: Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.
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