Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging

Abstract

Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches.

Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

“…A recent profiling highlighted that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs were significantly modified (Merimi et al, 2021a). In particular, inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNF-α and CCL5 cytokine expression.…”

The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings

“…MSCs effectively participate in the tissue repair process through their immunomodulatory, trophic antibacterial, antifibrotic, and proangiogenic functions ( Huayllani et al, 2020 ). MSCs also play a central role during the wound-healing process by coordinating between local cells/progenitors, cytokines, chemokines, and extracellular matrix proteins ( Zahorec et al, 2015 , Merimi et al, 2021a ). Under specific conditions, BM-MSCs may directly or indirectly favor the generation and proliferation of local progenitors, such as endothelial cells and fibroblasts ( Hu and Li, 2018 ; Kucharzewski et al, 2019 ; Shojaei et al, 2019 ).…”

Integrated transcriptome-proteome analyses of human stem cells reveal source-dependent differences in their regenerative signature

“…However, routine phenotypic characterizations alone cannot be used to identify differences in the functional properties of these cells, which has been reflected in the lack of consistent and reproducible success in many MSC-related clinical trials. Recently, several groups have attempted to compare molecular and functional similarities among multiple sources of MSCs using independent omics-based methods; i.e., transcriptional profiling ( Elahi et al., 2016 ; Merimi et al., 2021 ; Sargent et al., 2018 ), proteomics ( Billing et al., 2016 ; Kehl et al., 2019 ), and secretome analysis ( Mizukami et al., 2019 ; Petrenko et al., 2020 ; Shin et al., 2021 ; Wangler et al., 2021 ). However, while data gleaned from these studies somewhat complement conclusions drawn from phenotypic analysis, one major drawback is that each of these studies focus on a different profiling methodology, which makes it difficult to establish a molecular equivalency among the various datasets.…”