Mechanisms of the immunosuppressive effects of mouse adipose tissue-derived mesenchymal stromal cells on mouse alloreactively stimulated spleen cells

Nagaya, Ryo; Mizuno‐Kamiya, Masako; Takayama, Eiji; Kawaki, Harumi; Onoe, Ippei; Tanabe, Toshiichiro; Nagahara, Kuniteru; Kondoh, Nobuo

doi:10.3892/etm.2013.1382

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…MSC were capable of inhibiting CD4 + cell activation (according to the decreased expression of CD69 and increased expression of CD62L on CD4 + cells in the presence of MSC, S1 Fig), i.e. exhibited characteristic immunosuppressive functions described in other studies [30–32]. …”

Section: Resultsmentioning

confidence: 55%

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

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 55%

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

et al. 2017

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“…These cells also protect against organ rejection and prevent from graft versus host disease after allogeneic stem cell transplantation (Yañez et al 2006). Immunomodulatory properties have been confirmed both in vitro and in vivo (Baer 2014; Le Blanc et al 2003; Nagaya et al 2014; Patel et al 2008). …”

Section: Paracrine and Immunomodulatory Properties Of Ascsmentioning

confidence: 94%

Adipose-Derived Stem Cells as a Tool in Cell-Based Therapies

Bajek

Gurtowska

Olkowska

et al. 2016

Arch. Immunol. Ther. Exp.

144

108

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Recent development in stem cell isolation methods and expansion under laboratory conditions create an opportunity to use those aforementioned cells in tissue engineering and regenerative medicine. Particular attention is drawn towards mesenchymal stem cells (MSCs) being multipotent progenitors exhibiting several unique characteristics, including high proliferation potential, self-renewal abilities and multilineage differentiation into cells of mesodermal and non-mesodermal origin. High abundance of MSCs found in adipose tissue makes it a very attractive source of adult stem cells for further use in regenerative medicine applications. Despite immunomodulating properties of adipose-derived stem cells (ASCs) and a secretion of a wide variety of paracrine factors that facilitate tissue regeneration, effectiveness of stem cell therapy was not supported by the results of clinical trials. Lack of a single, universal stem cell marker, patient-to-patient variability, heterogeneity of ASC population combined with multiple widely different protocols of cell isolation and expansion hinder the ability to precisely identify and analyze biological properties of stem cells. The above issues contribute to conflicting data reported in literature. We will review the comprehensive information concerning characteristic features of ASCs. We will also review the regenerative potential and clinical application based on various clinical trials.

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“…AD-MSCs also express several kinds of growth factor receptors and by secretion of various cytokines and growth factors such as interleukin (IL)-6, IL-8, IL-10, HGF, VEGF, or FGF2, exhibit immunomodulatory, angiogenic, and antiapoptotic properties, in vitro or in vivo (Kilroy et al, 2007;De Francesco et al, 2015). AD-MSCs can act to suppress the proliferation and function of activated lymphocytes, inhibit the production of proinflammatory cytokines, and induce regulatory T cells (Patel et al, 2008;Gonzalez-Rey et al, 2010;Nagaya et al, 2014). AD-MSCs are also capable to reduce the damage, promote regeneration, or restore function of different tissues such as nervous system, heart, liver, or pancreas (Salgado et al, 2010;Zack-Williams et al, 2015;Bajek et al, 2016).…”

Section: Figmentioning

confidence: 99%

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

Hoseini

Ghazavi

Forouzanfar

et al. 2017

DNA and Cell Biology

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The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCs), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCs was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSC-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p < 0.001). In conclusion, the AD-MSCs efficiently secreted functional FGF1, which promoted angiogenic proliferation. Using AD-MSCs may provide a useful strategy in cell therapy, which can merge the beneficial effects of stem cells with the positive biological effects of FGF1 in various disorders, especially tissue defects, neurodegenerative, cardiovascular and diabetes endocrine pathologies, which remain to be tested in preclinical and clinical studies.

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Mechanisms of the immunosuppressive effects of mouse adipose tissue-derived mesenchymal stromal cells on mouse alloreactively stimulated spleen cells

Cited by 15 publications

References 29 publications

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

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

Adipose-Derived Stem Cells as a Tool in Cell-Based Therapies

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

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