Abstract
Mesenchymal stem/stromal cells (MSCs) exhibit multidifferentiation potential, paralleled with immunomodulatory and trophic properties that make them viable alternative tools for the treatment of degenerative disorders, allograft rejection, autoimmune diseases, and tissue regeneration. MSC functional attributes can be modulated by exposing them to inflammatory-stimulating microenvironments (i.e., priming) before their therapeutic use. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that plays key roles in immune response and hematopoiesis modulation through direct effects on hematopoietic progenitors' proliferation, survival, and mobilization. Despite the established roles of MSCs supporting hematopoiesis, the effects of G-CSF on MSCs biology have not been thoroughly explored. This study reveals that G-CSF has also direct effects on adipose-derived MSCs (ADSCs), modulating their functions. Herein, microarray-based transcriptomic analysis shows that G-CSF stimulation in vitro results in modulation of various signaling pathways including ones related with the metabolism of hyaluronan (HA), conferring a profile of cell mobilization to ADSCs, mediated in a cell-intrinsic fashion in part by reducing CD44 expression and HA synthesis-related genes. Collectively, these data suggest a direct modulatory effect of G-CSF on ADSC function, potentially altering their therapeutic capacity and thus the design of future clinical protocols.
Highlights
Mesenchymal stem/stromal cells (MSCs) have emerged in recent years as potential therapeutic tools for various clinical conditions [1, 2]
We show that two different formulations of recombinant human G-CSF (rhG-CSF) have in vitro modulatory effects to the transcriptome of Adipose-derived MSCs (ADSCs), inducing the activation of signaling pathways related to cell proliferation, mobilization, differentiation, and secondary immune responses
Expanded ADSCs exhibited a conserved potential to differentiate into osteoblasts (Figure 1(b)), indicating that all populations were comprised of multipotent MSC
Summary
Mesenchymal stem/stromal cells (MSCs) have emerged in recent years as potential therapeutic tools for various clinical conditions [1, 2]. MSCs are starting to be recognized by their ability to sense their surrounding molecular environment [7, 8] and to subsequently react with a broad range of responses involving the paracrine secretion of soluble and microvesicle-packaged molecules including growth factors, cytokines, and miRNAs [9, 10]. Those responses can be antagonizing, as proinflammatory and anti-
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