Abstract
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a multitude of tissues. In this context, the microenvironment of nasal polyp tissue has several inflammatory cells, but their stroma compartment remains little elucidated. Hence, we isolated MSCs from nasal polyps Polyp-MSCs (PO-MSCs) and compared their molecular features and gene expression pattern with bone marrow-derived MSCs (BM-MSCs). Initially, both PO-MSCs and BM-MSCs were isolated, cultivated, and submitted to morphologic, differentiation, phenotypic, immunosuppressive, and gene expression assays. Compared to BM-MSCs, PO-MSCs showed normal morphology and similar osteogenic/adipogenic differentiation potential, but their immunophenotyping showed lack of immune-associated molecules (e.g., CD117, HLA-DR, PDL-1, and PDL-2), which was linked with less immunoregulatory abilities such as (i) inhibition of lymphocytes proliferation and (ii) regulatory T cell expansion. Furthermore, we detected in the PO-MSCs a distinct gene expression profile in comparison with BM-MSCs. PO-MSC expressed higher levels of progenitor stem cells specific markers (e.g., CD133 and ABCB1), while BM-MSCs showed elevated expression of cytokines and growth factors (e.g., FGF10, KDR, and GDF6). The gene ontology analysis showed that the differentially modulated genes in PO-MSC were related with matrix remodeling process and hexose and glucose transport. For BM-MSCs, the highly expressed genes were associated with behavior, angiogenesis, blood vessel morphogenesis, cell–cell signaling, and regulation of response to external stimulus. Thus, these results suggest that PO-MSCs, while sharing similar aspects with BM-MSCs, express a different profile of molecules, which presumably can be implicated in the development of nasal polyp tissue.
Highlights
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a set of pro-regenerative studies [1]
The PO-MSCs in comparison with bone marrow-derived MSCs (BM-MSCs) had reduced expression of molecules related to immune regulation process, e.g., CD117, HLA-DR, PD-L1, and PD-1 ligand 2 (PD-L2) (Figure 1E; Figure S2 and Table S1 in Supplementary Material)
Our results showed that several MSCs immune-associated membrane markers CD117, HLA-DR, PD-L1, and PD-L2 were not expressed in PO-MSCs but were expressively present in BM-MSCs
Summary
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a set of pro-regenerative studies [1]. Two major factors are related to nasal polyp formation: an abnormal remodeling response, creating a mechanical dysfunction [7, 8] and a lack of immune regulatory effects, favoring a severe inflammatory process [9] In this sense, MSCs have a great therapeutic potential, showing specific immunomodulatory effects and an ability to directly or indirectly modulate the fibrotic process [10,11,12]. These two MSCs abilities could have an immediate impact on NP, mitigating the tissue inflammation and rebalancing the remodeling process In this context, our group and others’ recent studies have demonstrated a potential role of bone marrow-derived MSCs (BM-MSCs) in the modulation of several immune cells in inflamed nasal polyp tissue [13, 14]. Considering this perspective, MSCs derived from nasal polyps could show different features, which would participate in the regulation of NP microenvironment, eliciting favorable conditions for polyp development
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