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      The interplay between adipose-derived stem cells and bladder cancer cells

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      Scientific Reports
      Nature Publishing Group UK

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          Abstract

          Tissue engineering approaches offer alternative strategies for urinary diversion after radical cystectomy. Possible triggering of cancer recurrence remains, however, a significant concern in the application of stem-cell based therapies for oncological patients. Soluble mediators secreted by stem cells induce tissue remodelling effects, but may also promote cancer cells growth and metastasis. We observed a substantial increase in the concentration of IL-6 and IL-8 in the secretome of adipose-derived stem cells (ASCs) co-cultured with bladder cancer cells. Concentrations of GM-CSF, MCP-1 and RANTES were also elevated. Bioactive molecules produced by ASCs increased the viability of 5637 and HT-1376 cells by respectively 15.4% and 10.4% (p < 0.0001). A trend in reduction of adhesion to ECM components was also noted, even though no differences in β-catenin expression were detected. When HT-1376 cells were co-cultured with ASCs their migration and invasion increased by 24.5% (p < 0.0002) and 18.2% (p < 0.002). Expression of p-ERK1/2 increased in 5637 cells (2.2-fold; p < 0.001) and p-AKT in HB-CLS-1 cells (2.0-fold; p < 0.001). Our results confirm that ASCs crosstalk with bladder cancer cells in vitro what influences their proliferation and invasive properties. Since ASCs tropism to tumour microenvironment is well documented their application towards post-oncologic reconstruction should be approached with caution.

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          Effect of the Microenvironment on Mesenchymal Stem Cell Paracrine Signaling: Opportunities to Engineer the Therapeutic Effect.

          Cues from the extracellular environment, including physical stimuli, are well known to affect mesenchymal stem cell (MSC) properties in terms of proliferation and differentiation. Many therapeutic strategies are now targeting this knowledge to increase the efficacy of cell therapies, typically employed to repair tissue functions in the event of injury, either by direct engraftment into the target tissue or differentiation into mature tissues. However, it is now envisioned that harnessing the repertoire of factors secreted by MSCs (termed the secretome) may provide an alternate to these cell therapies. Of current interest are both direct protein secretions and two major subpopulations of bioactive extracellular vesicles (EVs), namely exosomes and microvesicles. EVs released by MSCs are reflective of their cells of origin, able to impact upon the activities of other cells in the local microenvironment, making the rational design of MSC paracrine activities an encouraging strategy to reproducibly modulate cell therapies. The precise mechanisms by which the secretome is modulated by the microenvironment, however, remain elusive. Controlling MSC growth conditions with oxygen tension, growth factor composition, and mechanical properties may serve to directly influence paracrine activity. Our growing understanding implicates components of the mechanotransduction machinery in translating both mechanical and chemical cues from the environment into alterations in gene regulation and varied paracrine activity. As technologies are developed to manufacture MSCs, advances in bioengineering and novel insight of how the extracellular environment affects MSC paracrine activity will play a pivotal role in the generation of widespread, successful, clinical MSC therapies.
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            Concise Review: Cancer Cells, Cancer Stem Cells, and Mesenchymal Stem Cells: Influence in Cancer Development

            Abstract Tumors are composed of different types of cancer cells that contribute to tumor heterogeneity. Among these populations of cells, cancer stem cells (CSCs) play an important role in cancer initiation and progression. Like their stem cells counterpart, CSCs are also characterized by self‐renewal and the capacity to differentiate. A particular population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into cells of mesodermal characteristics. Several studies have reported the potential pro‐or anti‐tumorigenic influence of MSCs on tumor initiation and progression. In fact, MSCs are recruited to the site of wound healing to repair damaged tissues, an event that is also associated with tumorigenesis. In other cases, resident or migrating MSCs can favor tumor angiogenesis and increase tumor aggressiveness. This interplay between MSCs and cancer cells is fundamental for cancerogenesis, progression, and metastasis. Therefore, an interesting topic is the relationship between cancer cells, CSCs, and MSCs, since contrasting reports about their respective influences have been reported. In this review, we discuss recent findings related to conflicting results on the influence of normal and CSCs in cancer development. The understanding of the role of MSCs in cancer is also important in cancer management. Stem Cells Translational Medicine 2017;6:2115–2125
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              MSCs-Derived Exosomes: Cell-Secreted Nanovesicles with Regenerative Potential

              Exosomes are membrane-enclosed nanovesicles (30–150 nm) that shuttle active cargoes between different cells. These tiny extracellular vesicles have been recently isolated from mesenchymal stem cells (MSCs) conditioned medium, a population of multipotent cells identified in several adult tissues. MSCs paracrine activity has been already shown to be the key mediator of their elicited regenerative effects. On the other hand, the individual contribution of MSCs-derived exosomes for these effects is only now being unraveled. The administration of MSCs-derived exosomes has been demonstrated to restore tissue function in multiple diseases/injury models and to induce beneficial in vitro effects, mainly mediated by exosomal-enclosed miRNAs. Additionally, the source and the culture conditions of MSCs have been shown to influence the regenerative responses induced by exosomes. Therefore, these studies reveal that MSCs-derived exosomes hold a great potential for cell-free therapies that are safer and easier to manipulate than cell-based products. Nevertheless, this is an emerging research field and hence, further studies are required to understand the full dimension of this complex intercellular communication system and how it can be optimized to take full advantage of its therapeutic effects. In this mini-review, we summarize the most significant new advances in the regenerative properties of MSCs-derived exosomes and discuss the molecular mechanisms underlying these effects.
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                Author and article information

                Contributors
                m.maj@cm.umk.pl
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 October 2018
                11 October 2018
                2018
                : 8
                : 15118
                Affiliations
                ISNI 0000 0001 0595 5584, GRID grid.411797.d, Chair of Urology, Department of Tissue Engineering, , Collegium Medicum, Nicolaus Copernicus University, ; Karlowicza 24, 85–092 Bydgoszcz, Poland
                Author information
                http://orcid.org/0000-0003-2433-8578
                Article
                33397
                10.1038/s41598-018-33397-9
                6181926
                30310111
                7409d0f1-ce64-43cc-ba6e-576a6a1f211e
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 31 May 2018
                : 26 September 2018
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