Background Bone marrow (BM)-derived mesenchymal stem cells (MSC) are currently under investigation for their potential role in the management of some autoimmune diseases. Besides their regenerative effects and ability to induce tissue repair, MSC seem to possess potent immunomodulatory and anti-inflammatory effects, either by direct cell-cell interaction or by secreting different molecules able to exert a paracrine effects on local environment.
Objectives Aim of the study was to evaluate the paracrine effects of BM-MSCs mesenchymal stem cells (MSC) isolated from normal individuals and patients with systemic sclerosis (SSc), on proliferation and cytokine production of cutaneous fibroblasts.
Methods Fibroblasts obtained from skin punch biopsies (10 dcSSc patients and 5 healthy donors -HD) were cultured in vitro. MSC were isolated by plastic adherence from SSc and HD bone marrow (BM). Co-cultures were assessed with HD or SSc fibroblasts with HD or SSc MSC. Fibroblast proliferation was assessed by WST-1 assay and data were expressed as median percentage of 3 replicates. Levels of TGF-β, Stem Cell Factor (SCF), and metalloproteinase MMP-9 were detected in the co-culture supernatants by commercial ELISA Kits.
Results Co-culture assays confirmed our previous results: an inhibition of SSc fibroblast proliferation, higher when fibroblasts were cultured with nBM MSCs (% of fibroblast proliferation vs fibroblasts without MSCs (100%): 75.8±9.9% with SSc MSCs vs 64.7±8.3% with nBM MSCs; P=0.038). In the presence of fibroblasts from healthy subjects, MSCs from normal and SSc BM equally inhibited proliferation. In comparison with basal values, the levels of the cytokines showed only in the presence of SSc fibroblasts and HD MSC a significant reduction in the content of SCF (mean±SD: 14.68±3.4 pg/ml vs 11.48±4.4; P=0.01) and TGF-β (3169.8±810 pg/ml vs 2450±900; P=0.0098), while no significant changes were observed in the presence of SSc MSC. As regards MMP-9, the basal value (mean±SD: 0.008±0.01 ng/ml) significantly increased in the presence of both HD (0.035±0.02; P=0.003) and SSc (0.094±0.072 ng/ml; P=0.01) MSC.
Conclusions Our findings demonstrate that normal MSC (more than SSc-MSC) may provide an important signal for skin fibroblasts, and particularly for SSc fibroblasts, by both exerting anti-proliferative effects and down-regulating their activation state. The present results may reinforce the perspective for a future use of BM-MSC as a therapeutic option in SSc, namely for their anti-fibrotic potential.
Disclosure of Interest None Declared
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