The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells

Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

doi:10.1016/j.cyto.2016.06.003

Cited by 108 publications

(78 citation statements)

References 63 publications

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“…This is true for different pathological contexts, especially inflammatory and degenerative affections; the implications of the inflammatory process, which arises in combination with ageing and during several human diseases, on MSC behaviour are reaching growing interest among researchers, but controversial and poor data are currently available. The effect of inflammatory cytokines has been studied on bone marrow and adipose MSCs, demonstrating the maintenance of cell morphology and, in some cases, the improvement of the immunomodulatory efficacy [23, 24]. Meanwhile, studies on aged mice demonstrated that bone marrow MSCs were less effective regarding their activation potential and immunomodulation, following a decreased cytokine expression [25].…”

Section: Discussionmentioning

confidence: 99%

The crosstalk between vascular MSCs and inflammatory mediators determines the pro-calcific remodelling of human atherosclerotic aneurysm

et al. 2017

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BackgroundHuman mesenchymal stem cells (MSCs) possess well-known reparative abilities, but any defect of the immunomodulatory activity and/or the differentiation process may determine the development of human diseases, including those affecting the vascular wall. MSCs residing within the human aortic wall represent a potential cell mediator of atherosclerotic aneurysm development.MethodsMSCs isolated from healthy and aneurysm aortas were characterized by flow cytometer and tested for differentiation properties. Healthy aorta (ha)-MSCs were then subjected to inflammatory stimuli to evaluate the microenvironmental impact on their function and involvement in vascular remodelling.ResultsAbdominal aortic aneurysm (AAA)-MSCs were isolated from calcified and inflamed aortas of 12 patients with high serum levels of MMP-9 protein. AAA-MSCs expressed typical mesenchymal markers and, in line with the histological analysis, elevated levels of OPN, an osteogenic marker also involved in vascular remodelling. AAA-MSCs were highly osteogenic and underwent intense calcium deposition under proper stimulation; moreover, AAA-MSCs were able to differentiate into tubule-like structures in Matrigel, even if the lack of CD146 and the reduced structural stability suggested an inefficient maturation process. We further demonstrated an association between osteogenesis and inflammation; indeed, ha-MSCs cultured with either cytokines (TNF-α, IL-1β) or AAA-PBMCs showed increased expression of MMP-9 and osteogenic markers, to the detriment of the adipogenic regulator PPAR-γ. Interestingly, the culture with inflammatory cells highly stimulated ha-MSCs towards the osteogenic commitment.ConclusionsAAA-MSCs displayed high osteogenic potential and pathological angiogenesis that represent crucial steps for AAA progression; we showed that the inflammatory process critically addresses human vascular MSCs towards a pathological behaviour, inducing vascular bone matrix deposition and remodelling. Inhibition of this pathway may represent a pharmacological approach against arterial calcification.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0554-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The crosstalk between vascular MSCs and inflammatory mediators determines the pro-calcific remodelling of human atherosclerotic aneurysm

et al. 2017

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“…In a proinflammatory environment, the interleukins IL-1β, IL-6, and IL-23 (mainly derived from Th17 cells) have been reported to increase the differentiation performance of human MSC toward the osteogenic and adipogenic lineages (Pourgholaminejad et al, 2016). Accordingly, TNFα, IL-1β, and IL-6 enhance osteoblast differentiation by triggering NF-κB signaling or modulating BMP2 pathway (Nakase et al, 1997; Hess et al, 2009; Huh and Lee, 2013; Croes et al, 2015).…”

Section: Microenvironment Factors Orchestrate Mscs Fatementioning

confidence: 99%

Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

Sobacchi

Palagano

Villa

et al. 2017

Front. Bioeng. Biotechnol.

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Mesenchymal stem cells (MSCs) are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

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“…In general, MSCs suppress inflammation, and pro-inflammatory cytokines increase the immunomodulatory capacity of MSCs (135–137). While MSCs have immunosuppressive effects in the context of vigorous inflammation, recent studies have demonstrated that low-level inflammation or inhibited expression of immunosuppressive factors such as NOS can result in MSC induction of immune response (18, 138).…”

Section: Pro-inflammatory Statementioning

confidence: 99%

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

et al. 2017

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Endocrine-disrupting chemicals (EDCs) are prevalent in the environment, and epidemiologic studies have suggested that human exposure is linked to chronic diseases, such as obesity and diabetes. In vitro experiments have further demonstrated that EDCs promote changes in mesenchymal stem cells (MSCs), leading to increases in adipogenic differentiation, decreases in osteogenic differentiation, activation of pro-inflammatory cytokines, increases in oxidative stress, and epigenetic changes. Studies have also shown alteration in trophic factor production, differentiation ability, and immunomodulatory capacity of MSCs, which have significant implications to the current studies exploring MSCs for tissue engineering and regenerative medicine applications and the treatment of inflammatory conditions. Thus, the consideration of the effects of EDCs on MSCs is vital when determining potential therapeutic uses of MSCs, as increased exposure to EDCs may cause MSCs to be less effective therapeutically. This review focuses on the adipogenic and osteogenic differentiation effects of EDCs as these are most relevant to the therapeutic uses of MSCs in tissue engineering, regenerative medicine, and inflammatory conditions. This review will highlight the effects of EDCs, including organophosphates, plasticizers, industrial surfactants, coolants, and lubricants, on MSC biology.

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The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells

Cited by 108 publications

References 63 publications

The crosstalk between vascular MSCs and inflammatory mediators determines the pro-calcific remodelling of human atherosclerotic aneurysm

The crosstalk between vascular MSCs and inflammatory mediators determines the pro-calcific remodelling of human atherosclerotic aneurysm

Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

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