Toll-Like Receptors as Modulators of Mesenchymal Stem Cells

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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“…TLRs are being proposed as firstline environmental danger sensors for stem cells (Delarosa et al, 2012;Martino and Pluchino 2007).…”

Section: Modulation Of Immune Responsesmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

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“…MSCs have also been reported to show antimicrobial activities against different pathogens upon activation with inflammatory cytokines [46] . Noteworthy in the context of sepsis, the functionality of MSCs can also be modulated by activators of TLRs [47] . It has been described that MSCs can be polarized in vitro towards either anti-inflammatory or pro-inflammatory phenotypes, depending on the TLR ligand time/ concentration used for activation [48] .…”

Section: Mscmentioning

confidence: 99%

Mesenchymal stem cells as a therapeutic tool to treat sepsis

Lombardo¹

2015

WJSC

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Sepsis is a clinical syndrome caused by a deregulated host response to an infection. Sepsis is the most frequent cause of death in hospitalized patients. Although knowledge of the pathogenesis of sepsis has increased substantially during the last decades, attempts to design effective and specific therapies targeting components of the derailed host response have failed. Therefore, there is a dramatic need for new and mechanistically alternative therapies to treat this syndrome. Based on their immunomodulatory properties, adult mesenchymal stem or stromal cells (MSCs) can be a novel therapeutic tool to treat sepsis. Indeed, MSCs reduce mortality in experimental models of sepsis by modulating the deregulated inflammatory response against bacteria through the regulation of multiple inflammatory networks, the reprogramming of macrophages and neutrophils towards a more antiinflammatory phenotype and the release of antimicrobial peptides. This report will review the current knowledge on the effects of MSC treatment in preclinical experimental small animal models of sepsis.

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“…Toll-like receptors (TLRs) stimulate MSC migration and osteogenic differentiation utilising NFk-b and PI3 kinase signalling pathways [48]. Additionally, macrophages existing in the fractured bone are a source of bone morphogenetic proteins (BMPs) and Oncostatin M that enhance the proliferation and osteogenic function of MSCs [49,50].…”

Section: Preparation For the Repair Phase; Licensing Of Mscsmentioning

confidence: 99%