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. 2017 Jan 2;16(1):33-44.
doi: 10.1080/15384101.2016.1211215. Epub 2016 Jul 27.

The secretome of MUSE cells contains factors that may play a role in regulation of stemness, apoptosis and immunomodulation

Nicola Alessio  1 , Servet Özcan  2   3 , Kazuki Tatsumi  4   5 , Ayşegül Murat  3 , Gianfranco Peluso  6 , Mari Dezawa  5 , Umberto Galderisi  1   2   7
Affiliations

The secretome of MUSE cells contains factors that may play a role in regulation of stemness, apoptosis and immunomodulation

Nicola Alessio et al. Cell Cycle. .

Abstract

Mesenchymal stromal cells (MSCs) are a heterogeneous population, which contain several cell phenotypes: mesenchymal stem cells, progenitor cells, fibroblasts and other type of cells. Previously, we identified unique stem cells that we named multilineage-differentiating stress enduring (Muse) cells as one to several percent of MSCs of the bone marrow, adipose tissue and dermis. Among different cell populations in MSCs, Muse cells, positive for pluripotent surface marker SSEA-3, may represent cells responsible for pluripotent-like property of MSCs, since they express pluripotency genes, able to differentiated into triploblastic cells from a single cells and are self-renewable. MSCs release biologically active factors that have profound effects on local cellular dynamics. A thorough examination of MSC secretome seems essential for understanding the physiological functions exerted by these cells in our organism and also for rational cellular therapy design. In this setting, studies on secretome of Muse cells may shed light on pathways that are associated with their specific features. Our findings evidenced that secretomes of MSCs and Muse cells contain factors that regulate extracellular matrix remodeling, ox-redox activities and immune system. Muse cells appear to secrete factors that may preserve their stem cell features, allow survival under stress conditions and may contribute to their immunomodulation capacity. In detail, the proteins belonging to protein kinase A signaling, FXR/RXR activation and LXR/RXR activation pathways may play a role in regulation of Muse stem cell features. These last 2 pathways together with proteins associated with antigen presentation pathway and coagulation system may play a role in immunomodulation.

Keywords: Mesenchymal stem cells; apoptosis; cancer; secretome; senescence.

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Figures

Figure 1.
Figure 1.
Cell cultures of Muse cells and MSCs. The figure shows representative fields of cell cultures from which we collected secretomes. Black bar represents 100 microns.
Figure 2.
Figure 2.
Overlapping networks. 159 canonical pathways were in common among Muse cells, bmMSCs and aMSCs. We determined for each cell type which of these belonged to overlapping networks. The picture shows overlapping networks in Muse cells (A), in bmMSCs (B) and aMSCs (C).
Figure 2.
Figure 2.
(Continued).
Figure 2.
Figure 2.
(Continued).
Figure 3.
Figure 3.
Muse cells canonical pathways in overlapping networks. The figure shows the canonical pathways of Muse cells, which belongs to overlapping networks. Proteins of Muse cells secretome for each canonical pathway are depicted.
Figure 4.
Figure 4.
Experimental plan. Suggested experimental plan to identify the role of specific factors present in cells' secretome.
See this image and copyright information in PMC

Comment in

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