Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and suppress the growth of MCF-7 human breast cancer cells

Ryu, Hojun; Oh, Ji Eun; Rhee, Ki Jong; Baik, Soon Koo; Kim, Jiye; Kang, Seong Joon; Sohn, Joon Hyung; Choi, Eun Hee; Shin, Ha Cheol; Kim, Yong Man; Kim, Hyun Soo; Bae, Keum Seok; Eom, Young Woo

doi:10.1016/j.canlet.2014.06.018

Cited by 88 publications

(57 citation statements)

References 29 publications

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“…Our work showed that among different MSC types those derived from the adipose tissue were the most sensitive to dsRNA presence in the cytoplasm as even at the lowest ligand concentration, the production of IFN-β was quite high. AT-MSCs were also described to produce IFN-β when cultured at high density 29 . Type I interferons (IFNs) are a family of cytokines involved in the immunity against viruses and other intracellular infections 30 .…”

Section: Discussionmentioning

confidence: 99%

Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells

Raicevic

Najar

Busser

et al. 2017

Sci Rep

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Due to their immunomodulatory and regenerative properties, Mesenchymal stromal cells (MSC) have generated major interests in several clinical settings including transplantation and inflammatory diseases. MSC functions can be influenced by their tissue origin. Their microenvironment strongly affects their biology notably through TLR sensing. In this study, we show that MSC isolated from four different sources express another type of cytosolic pathogen recognition receptors known as retinoic acid inducible gene-I (RIG-I)-like receptors (RLR). RLR activation in MSC induces the production of Type I IFN (IFN-β) and Type III IFN (IFN-λ1). The highest producers are adipose tissue(AT)-MSC. We further show that Interferon production is induced through TBK1/IKK-ε signaling and IRF7 phosphorylation. Depending on MSC source, the knockdown of TLR3 and/or RIG-I decreases the MSC response to RLR ligand poly(I:C)/Lyovec. Among the different MSC types, AT-MSCs display the highest sensitivity to viral stimuli as shown by the alteration of their viability after prolonged stimulation. Our work indicates that this could be linked to an increase of pro-apoptotic Noxa expression. Finally, the expression of IDO1 and LIF upon RLR activation indicate the increase of MSC immunomodulatory potential, especially in AT-MSCs. Altogether, these data should be considered when designing MSC-based therapy in clinical settings where inflammation or infection are present.

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Section: Discussionmentioning

confidence: 99%

Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells

Raicevic

Najar

Busser

et al. 2017

Sci Rep

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“…The role of ASCs in regulating breast cancer is confounding due to varied nature of secreted adipokines, such as CCL5, which enhances the motility of MCF-7 breast cancer cell in vitro [212]. In contrast to this, another study reported that high density ADSC-CM inhibited the MCF-7 [213]. Though the contradictory impact of ASCs and its secretome is wide in literature, it has been proposed that ASCs might only promotes cancer in active breast cancer cells [214].…”

Section: Asc Secretome and Its Therapeutic Effectmentioning

confidence: 99%

Revisiting the Advances in Isolation, Characterization and Secretome of Adipose-Derived Stromal/Stem Cells

Dubey

Mishra²,

Dubey

et al. 2018

IJMS

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Adipose-derived stromal/stem cells (ASCs) seems to be a promising regenerative therapeutic agent due to the minimally invasive approach of their harvest and multi-lineage differentiation potential. The harvested adipose tissues are further digested to extract stromal vascular fraction (SVF), which is cultured, and the anchorage-dependent cells are isolated in order to characterize their stemness, surface markers, and multi-differentiation potential. The differentiation potential of ASCs is directed through manipulating culture medium composition with an introduction of growth factors to obtain the desired cell type. ASCs have been widely studied for its regenerative therapeutic solution to neurologic, skin, wound, muscle, bone, and other disorders. These therapeutic outcomes of ASCs are achieved possibly via autocrine and paracrine effects of their secretome comprising of cytokines, extracellular proteins and RNAs. Therefore, secretome-derivatives might offer huge advantages over cells through their synthesis and storage for long-term use. When considering the therapeutic significance and future prospects of ASCs, this review summarizes the recent developments made in harvesting, isolation, and characterization. Furthermore, this article also provides a deeper insight into secretome of ASCs mediating regenerative efficacy.

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“…Moreover, in this study it has been demonstrated that MSCs, induced for IL-15 expression, stimulate accumulation of NK cells and CD8 + T lymphocytes, thus supporting antitumor immune response [133]. Also, it has been shown that IFN- β -producing MSCs from bone marrow [134], as well as adipose tissue [135], inhibit proliferation of hepatocellular carcinoma or breast cancer, respectively. Additionally, it has been reported that IFN- β -producing bone marrow MSCs attenuate proliferation of hepatocellular carcinoma cells, modifying their cell cycle, decreasing expression of cyclin D1 and phosphorylation of Rb via suppressed Akt and stimulated FOXO3a activity [134].…”

Section: Antitumor Features Of Mscsmentioning

confidence: 99%

“…Additionally, it has been reported that IFN- β -producing bone marrow MSCs attenuate proliferation of hepatocellular carcinoma cells, modifying their cell cycle, decreasing expression of cyclin D1 and phosphorylation of Rb via suppressed Akt and stimulated FOXO3a activity [134]. On the other side, it has been shown that IFN- β -producing adipose tissue MSCs exert cytotoxic effect on breast tumor cells mediated by STAT1 activation [135]. …”

Section: Antitumor Features Of Mscsmentioning

confidence: 99%

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

Trivanović

Krstić

Djordjević

et al. 2016

Mediators of Inflammation

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State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

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Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and suppress the growth of MCF-7 human breast cancer cells

Cited by 88 publications

References 29 publications

Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells

Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells

Revisiting the Advances in Isolation, Characterization and Secretome of Adipose-Derived Stromal/Stem Cells

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

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