Immunomodulation by Mesenchymal Stromal Cells and Their Clinical Applications

Abstract

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that can be isolated and expanded from various sources. MSCs modulate the function of immune cells, including T and B lymphocytes, dendritic cells, and natural killer cells. An understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms involved in MSCs-mediated therapeutic effects, and for designing more practical protocols for the clinical use of these cells. In this review we describe the current knowledge of the unique biological properties of MSCs, the immunosuppressive effects on immune-competent cells and the paracrine role of soluble factors. A summary of the participation of MSCs in preclinical and clinical studies in treating autoimmune diseases and other diseases is described. We also discuss the current challenges of their use and their potential roles in cell therapies.

Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

“…9,10 Nevertheless, one advantage of BM-MSCs over other cell types is their relatively short culture time. 11,33 The role of inflammation in the pathogenesis of arterial hypertension, particularly in activating the sympathetic nervous system, has been recently identified in a study using a murine model. 34 Penn et al observed that BM transplantation from spontaneously hypertensive rats into normotensive rats resulted in a marked increase in blood pressure; however, treating the rats with minocycline, a second-generation semisynthetic tetracycline and microglial activation inhibitor with anti-inflammatory effects, reversed the hypertension.…”

“…haematopoietic) stem cell transplantation, graft-versus-host disease (GVHD)-in which immunocompetent donor cells recognise and attack tissues in an immunocompromised host-is a significant cause of morbidity and mortality. 11 Traditional management entails immunosuppression with corticosteroids as first-line therapy, a treatment that produces sustained responses in <40-50% of patients with GVHD. 43 However, corticosteroid-refractory patients require effective second-and third-line treatment options.…”

“…5 Additionally, due to the immunomodulatory effects of human AT-MSCs, AT is an excellent source of MSCs for allogeneic transplants and, as AT-MSCs do not express major histocompatibility complex type II antigens, the risk of rejection is minimised. 11…”

“…Furthermore, these cells secrete soluble factors, such as IL-10, transforming growth factor-β and prostaglandin E2, making these cells immunosuppressive. 5,11 It should be noted that the p53 protein plays a key role in the differentiation of human AT-MSCs cells, affecting their osteogenic and adipogenic potential by suppressing the osterix, runt-related transcription factor and peroxisome proliferator-activated receptor (PPAR) genes. 51 In various malignancies, p53 function is limited, thus offering the possibility of using cancer cells from mutant MSCs to investigate treatment targets.…”

Effect of Bone Marrow‐Derived Mesenchymal Stem Cells on Cochlear Function in an Experimental Rat Model

“…The immunoregulatory properties of MSCs have been shown in vitro to modulate the action of neutrophils, NK cells as well as B and T lymphocytes (Demircan et al, 2013;Spees et al, 2016). MSCs possess immunosuppressive properties and this is due to the secretion of soluble factors including HGF, TGF-β, IDO, NO, and PGE2 (De Miguel et al, 2012;Abumaree et al, 2017;Cagliani et al, 2017). Paracrine factors influence the microenvironment and activate local organ-specific progenitor populations, leading to long-term therapeutic effects.…”