Secretory factors produced by adipose mesenchymal stem cells downregulate Th17 and increase Treg cells in peripheral blood mononuclear cells from rheumatoid arthritis patients.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

We aimed to assess the immunoregulatory effects of secretory factors produced by adipose tissue-derived MSC (AT-MSC) on Th17 and Treg subsets from patients with rheumatoid arthritis (RA). 17 patients with active disease matching the ACR/EULAR 2010 criteria for RA were included. Patients' peripheral blood mononuclear cells (PBMC) were cultured in AT-MSC-conditioned medium (AT-MSCcm) and in control medium. The cytokine production of AT-MSC and PBMC was quantified by ELISA. Th17 and Treg were determined by flow cytometry. AT-MSCcm contained: IL-6, IL-17, IL-21, CCL2, CCL5, IL-8, sVEGF-A and PGE 2 . Cultivation of patients' PBMC with AT-MSCcm increased TGF-β1 (8318 pg/ml; IQR 6327-11,686) vs control medium [6227 pg/ml (IQR 1681-10,148, p = 0.013)]. PBMC cultivated with AT-MSCcm downregulated TNF-α, IL-17A, and IL-21 compared to control PBMC: 5 pg/ml IQR (1.75-11.65) vs 1 pg/ml (IQR 0.7-1.9), p = 0.001; 4.2 pg/ml (IQR 3.1-6.1) vs 2.3 pg/ml (IQR.75-5.42), p = 0.017; 66.9 pg/ml (IQR 40.6-107.2) vs 53 pg/ml (IQR 22-73), p = 0.022. Th17 decreased under the influence of AT-MSCcm: 10.13 ± 3.88% vs 8.98 ± 3.58%, p = 0.02. CD4 + FoxP3 + , CD4 + CD25 - FoxP3 + , and CD4 + CD25 + FoxP3 + was 11.35 ± 4.1%; 7.13 ± 3.12% and 4.22 ± 2% in control PBMC. Accordingly, CD4 + FoxP3 + , CD4 + CD25 - FoxP3 + , and CD4 + CD25 + FoxP3 + significantly increased in PBMC cultured with AT-MSCcm: 15.6 ± 6.1%,

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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