Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation

Abstract

Recent evidence indicates that mesenchymal stem cells (MSC) derived from early embryonic tissues have better therapeutic ability as compared with adult tissue-derived stem cells. In the present study, we transplanted human early embryonic MSC (hMSC) into MRL/Lpr mice via tail vein injection to observe the therapeutic efficacy of hMSC and their impact on T helper 17 (Th17) cell differentiation in MRL/Lpr mice. Animals in hMSC treatment group received hMSC (1 Â 10 6 /200 mL) via the tail vein at the age of 16 and 19 weeks. We found that hMSC treatment prolonged the survival of MRL/Lpr mice without inducing tumorigenesis, reduced urine protein, and alleviated the renal pathologic changes. In addition, it reduced the proportion of Th17 cells in the spleen of MRL/Lpr mice and the serum interleukin 17 (IL-17) concentration. Our in vitro experiment also demonstrated that hMSC could secrete Th17 differentiation-related cytokines of PGE2, IL-10 and TGF-b, and IFN-g stimulation up-regulated the secretion of these immune regulating factors. The results of the present study suggest that hMSC therapy could alleviate systemic and local renal lesions in MRL/Lpr mice, probably by secreting immune regulating factors and regulating Th17 cell differentiation in MRL/Lpr mice. ARTICLE HISTORY

Xenogeneic Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Renal Injury and Reduces Inflammation in a Mouse Model of Lupus Nephritis

“…MSC transplantation has been considered an ideal treatment method for LN due to their plentiful sources, low immunogenicity, and lack of ethical issues. Studies have demonstrated that xenogeneic MSC administration leads to improvement of the renal injury in MRL/lpr mice [19–22]. Choi, E. W. et al [5] showed that xenogeneic transplantation of adipose tissue-derived MSCs initiated a strong humoral immune response, improved the symptoms of LN in the (NZB × NZW) F1 mice, and had many advantages, such as convenient and abundant sources and ease of isolation, culture, amplification, and purification.…”

Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis

“…Seven studies [11,13,16,[22][23][24]37] were included to assess the effects of MSC on BUN. The results showed that the difference in BUN levels between the MSC group and the control group was notable (OR = − 14.57, 95% CI − 20.50, − 8.64; P < 0.00001; Table 2), and the MSC group had lower levels of BUN.…”

“…The albumin levels were also detected, and two studies [10,23] were recruited. The results showed that the MSC group had higher levels of albumin, and the difference in albumin levels between the MSC group and the control group was notable (OR = 7.22, 95% CI 3.74, 10.69; P < 0.0001; Table 2).…”

“…The levels of TGF-β, MCP-1, IFN-γ, TNF-α, Th1, Th17, Foxp3, and Tregs were detected; three studies [10,18,24] for TGF-β, two studies [11,37] for MCP-1, four studies [12,20,24,30] for IFN-γ, six studies [12,16,20,24,35,37] for TNF-α, three studies [19,23,37] for Th1, four studies [19,23,26,36] for Th17, two studies [10,11] for Foxp3, and three studies [19,23,36] for Tregs were included for the assessment of the effect of MSC treatment on other cytokines. Interestingly, the MSC treatment group had a lower level of IFN-γ when compared with the control group (OR = − 240.24, 95% CI − 364.73, − 115.75; P = 0.0002; Table 2).…”

Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications

“…In the same study [42], TGF-β was shown to stimulate Tregs both in vitro and in vivo in SLE patients. In addition, TGF-β is involved in inhibiting the immune response by suppressing dendritic cell (DC) maturation [43] and T-helper 17 (Th17) cell generation [44]. MSCs secrete metalloproteinases (MMPs) that are able to halt CC (C–C motif) chemokines such as CCL2 (targeting chemokine (C–C motif) ligand 2).…”