Mesenchymal stromal cells and immunomodulation: A gathering of regulatory immune cells

Najar, Mehdi; Raicevic, Gordana; Fayyad‐Kazan, Hussein; Bron, Dominique; Toungouz, Michel; Lagneaux, Laurence

doi:10.1016/j.jcyt.2015.10.011

Cited by 226 publications

(201 citation statements)

References 118 publications

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…Mechanistically, immunomodulation occurs by different pathways but two important sides have to be taken into account: the regulatory network of factors and the gathering of regulatory immune cells. These pathways compete to establish a tolerogenic state conducive for immunomodulation (1617). …”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

“…MSCs and NK cells have been described to interact in a complex manner with bidirectional regulatory effects. Although they are able to alter most of activated NK cell biology, MSCs are reported to be susceptible to NK-cell mediated lysis (17). The results of Giuliani M. et al, showed that TLR3-primed (poly(I:C)) BM-MSCs were more resistant than unprimed MSCs to IL-2-activated NK-induced killing (99).…”

Section: Msc Immunomodulation and Tlr-primingmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

et al. 2017

Self Cite

View full text Add to dashboard Cite

Mesenchymal Stromal Cells (MSCs) are potential cellular candidates for several immunotherapy purposes. Their multilineage potential and immunomodulatory properties make them interesting tools for the treatment of various immunological diseases. However, depending on the local microenvironment, diverse biological functions of MSCs can be modulated. Indeed, during infections such as obtained following TLR-agonist engagement (called as TLR priming), the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs can present critical changes, which could further affect their therapeutic potential. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects in particular during infectious episodes and to find the suitable experimental settings to study that. Pre-stimulation of MSCs with a specific TLR ligand may serve as an effective priming step to modulate one of its function to achieve a desired therapeutic issue.

show abstract

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

Section: Msc Immunomodulation and Tlr-primingmentioning

confidence: 99%

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, MSC secret regulatory molecules able to modulate the immune response [12]. Once induced, MSCs should be defined as coordinators of the immune system by providing a tolerogenic environment for both innate and adaptive response [16].…”

Section: Cd25mentioning

confidence: 99%

Adipose derived stem cells for regenerative therapy in osteoarticular diseases

Pers

Jørgensen

2016

Hormone Molecular Biology and Clinical Investigation

View full text Add to dashboard Cite

Abstract:In the recent years, adipose derived stem cells (ASCs) led to significant findings in the field of regenerative therapy. ASCs have various biological properties and capacity as differentiation in three lineages (chondrocytes, osteocytes and adipocytes) or immunomodulation by releasing paracrine factors. Osteoarthritis (OA) is the most frequent osteoarticular disease characterized by none curative treatment. We reviewed all current data on the proof of concept of ASCs in OA pathophysiology as well as an inventory of ASC promising cell therapy in OA.

show abstract

“…The concept is based on the immune regulatory, mainly immune suppressive, properties of MSC [1–4]. The suppressive activity of MSC towards T cells was first demonstrated by di Nicola and co-authors who showed inhibition of T cell proliferation in vitro in the presence of MSC [5].…”

Section: Introductionmentioning

confidence: 99%

“…The cells were shown to inhibit maturation and functions of various immune cells, including macrophages, dendritic cells, NK cells, Th1 and Th17 lymphocytes [6–12]. Recent studies have demonstrated that MSC possess rather immunoregulatory than immunosuppressive properties, and may inhibit, sustain or stimulate effector cell functions depending on the microenvironment [1, 2, 4]. Pro-inflammatory conditions activate MSC to produce suppressive mediators and promote their inhibitory properties [13–16].…”

Section: Introductionmentioning

confidence: 99%

The introduction of mesenchymal stromal cells induces different immunological responses in the lungs of healthy and M. tuberculosis infected mice

et al. 2017

View full text Add to dashboard Cite

Mesenchymal stromal cells (MSC) have strong immunomodulatory properties and therefore can be used to control inflammation and tissue damage. It was suggested recently that MSC injections can be used to treat multi-drug resistant tuberculosis (TB). However, MSC trafficking and immunomodulatory effects of MSC injections during Mycobacterium tuberculosis (Mtb) infection have not been studied. To address this issue we have analyzed MSC distribution in tissues and local immunological effects of MSC injections in Mtb infected and uninfected mice. After intravenous injection, MSC accumulated preferentially in the lungs where they were located as cell aggregates in the alveolar walls. Immunological analysis of MSC effects included detection of activated, IFN-γ and IL-4 producing CD4+ lymphocytes, the frequency analysis of dendritic cells (CD11c+F4/80) and macrophages (CD11c-F4/80+) located in the lungs, the expression of IA/IE and CD11b molecules by these cells, and evaluation of 23 cytokines/chemokines in lung lysates. In the lungs of uninfected mice, MSC transfer markedly increased the percentage of IFN-γ+ CD4+ lymphocytes and dendritic cells, elevated levels of IA/IE expression by dendritic cells and macrophages, augmented local production of type 2 cytokines (IL-4, IL-5, IL-10) and chemokines (CCL2, CCL3, CCL4, CCL5, CXCL1), and downregulated type 1 and hematopoietic cytokines (IL-12p70, IFN-γ, IL-3, IL-6, GM-CSF). Compared to uninfected mice, Mtb infected mice had statistically higher “background” frequency of activated CD69+ and IFN-γ+ CD4+ lymphocytes and dendritic cells, and higher levels of cytokines in the lungs. The injections of MSC to Mtb infected mice did not show statistically significant effects on CD4+ lymphocytes, dendritic cells and macrophages, only slightly shifted cytokine profile, and did not change pathogen load or slow down TB progression. Lung section analysis showed that in Mtb infected mice, MSC could not be found in the proximity of the inflammatory foci. Thus, in healthy recipients, MSC administration dramatically changed T-cell function and cytokine/chemokine milieu in the lungs, most likely, due to capillary blockade. But, during Mtb infection, i.e., in the highly-inflammatory conditions, MSC did not affect T-cell function and the level of inflammation. The findings emphasize the importance of the evaluation of MSC effects locally at the site of their predominant post-injection localization and question MSC usefulness as anti-TB treatment.

show abstract

Mesenchymal stromal cells and immunomodulation: A gathering of regulatory immune cells

Cited by 226 publications

References 118 publications

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

Adipose derived stem cells for regenerative therapy in osteoarticular diseases

The introduction of mesenchymal stromal cells induces different immunological responses in the lungs of healthy and M. tuberculosis infected mice

Contact Info

Product

Resources

About