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

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.

Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth

“…In the context of neuroregeneration, pre-clinical and clinical findings show that these molecules can directly stimulate the recruitment, proliferation and differentiation of the endogenous cells [11,12]. Additionally, they can regulate local mechanisms such as apoptosis, scarring and revascularization, as well as modulate immune and inflammatory responses [9,13], thus contributing to reduce tissue damage.…”

Filamin B and CD13 are components of senescent secretomes that may be involved in primary (stress induced) and paracrine senescence of mesenchymal stromal cells

“…Although many studies highlighted the importance of the SASP in regulating cellular response to senescence signaling, the identification of secreted factors is still a challenging issue, since the typology of secreted proteins strictly depends on genotoxic stress and cell type (2)(3)(4). To date, a comprehensive analysis of the secretome profile of senescent MSCs is still lacking.…”

“…Cellular senescence is the permanent cell cycle arrest evoked in response to a variety of stressors (1). This physiological response to stress has a pleiotropic effect: i) beneficial, since senescence can counteract tumor growth by blocking the proliferation of transformed cells, ii) detrimental by contributing to organismal aging (2)(3)(4). Recently, it has been demonstrated that senescence may also contribute to organism development and tissue repair processes (5).…”

“…The beneficial functions of MSCs have been attributed to their autocrine and paracrine activity (13). Therefore, senescence of MSCs may have a great impact on body's health given that it can alters the composition of their secretome and can impair the key MSC biological functıons (3,4,14).…”

Biochemical Effects of Retinoid Derivatives on Mesenchymal Stem Cells In Vitro

“…Moreover, the multilineage-differentiating stress enduring cells seem to release biologically active factors able to maintain their broad stem features, to empower the survival when facing stress conditions and to sustain their immunomodulatory capacities. The described features of multilineagedifferentiating stress enduring cells are basically involving pathways as PKA signaling, as well as FXR/RXR and LXR/ RXR activations [2].…”