Transplantation of dental tissue-derived mesenchymal stem cells ameliorates nephritis in lupus mice
ANNALS OF TRANSLATIONAL MEDICINE
Authors: Tang, Xiaojun; Li, Wenchao; Wen, Xin; Zhang, Zhuoya; Chen, Weiwei; Yao, Genhong; Chen, Hongwei; Wang, Dandan; Shi, Songtao; Sun, Lingyun
Abstract
Background: Recently, clinical studies have suggested that transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) were able to alleviate clinical symptoms of refractory systemic lupus erythematosus (SLE). Although dental tissue derived MSCs, including dental pulp stem cells (DPSCs) and periodontal ligament stem cell (PDLSCs), have been reported to possess immunomodulatory functions, whether they can ameliorate SLE symptoms as UC-MSCs remains to be elucidated. Methods: We assessed the abilities of DPSCs and PDLSCs to treat SLE, cells were transferred intravenously to 28-week old B6/lpr mice. Ten weeks later, mice were sacrificed. Serum anti-dsDNA antibodies and anti-nuclear antibodies (ANA) were measured by ELISA. Renal pathology was analyzed by H&E, PAS and MASSON staining. Aggregation of IgG and IgM in the glomerulus was examined by immunofluorescence. Frequencies of Th1, Th2, Treg, Th17, Tfh, and plasma cells were determined by surface and intracellular staining. Serum IL-6, IL-10, IL-17 and MCP-1 were measured by Milliplex (R) MAP technology. Results: Same as UC-MSCs, both DPSCs and PDLSCs could efficiently downregulate 24-h proteinuria, anti-dsDNA antibodies and glomerular IgG/IgM in B6/lpr mice. However, DPSCs but not PDLSCs could ameliorate the glomerular lesion in B6/lpr mice. Compared to the phosphate buffered saline (PBS) group, percentages of Th1 (CD4(+)IFN gamma(+)) cells and plasma (B220(-)CD138(+)) cells in the spleen were significantly decreased in DPSCs and PDLSCs groups. There was no significant difference in Th2 (CD4(+)IL4(+)), Th17 (CD4(+)IL17(+)), Tfh (CD4(+)PD-1(+)CXCR5(+)) and Treg (CD4(+)CD25(+)Foxp3(+)) cells. Serum IL-6, IL-10, IL-17 and MCP-1 levels didn't change after MSCs transplantation. Conclusions: Our results show that both DPSCs and PDLSCs can alleviate the disease symptoms of lupus-prone B6/lpr mice. DPSCs are also effective in reducing kidney glomerular lesion and perivascular inflammation infiltration as well as UC-MSCs, suggesting that DPSCs might be another choice for SLE treatment.
Swimming improves cognitive reserve in ovariectomized rats and enhances neuroprotection after global cerebral ischemia
BRAIN RESEARCH
Authors: Zhang, Meng; Zhai, Yating; Sun, Yaping; Zhang, Wenli; Li, Qian; Brann, Darrell; Wang, Ruimin
Abstract
Cognitive reserve has been proposed to account for different responses to brain damage or pathology. Factors implicated to influence cognitive reserve include cognitive engagement, physical activity, leisure activities, stress levels, and diet. Furthermore, long-term ovariectomy (OVX), such as occurs in women that have underwent surgical menopause, has been reported to increase the risk of cognitive impairment. In the current study, we examined whether swimming improves cognitive function in long-term OVX-rats. We also examined the neuroprotective effect of swimming after global cerebral ischemia (GCI) and explored the effect of swimming preconditioning on activation of the MAPK cascade signaling pathway, synaptic proteins and brain-derived growth factor (BDNF) - all factors implicated in regulating synaptic plasticity and neuroprotection in the brain. Adult Sprague-Dawley OVX-rats were randomly assigned into four groups: Sham (Sh), Sham + Swimming (Sh + Sw), Ischemia/Reperfusion (IR) and IR + Sw. Our results revealed that (1) Morris water maze and shuttle box test analysis revealed that swimming improved cognitive function in OVX-rats, (2) The levels of PSD95 and synaptophysin, as well as the protein expression of p-ERR, p-CREB and BDNF were all increased in the hippocampus after swimming with or without GCI, and (3) Swimming also increased the number of surviving neurons and IL4 protein expression, while decreasing the Iba1 (a microglia marker) level in the hippocampus. In conclusion, our study demonstrates that swimming improves memory in OVX-rats, and that swimming preconditioning enhances the neuroprotective ERK1/2/CREB/BDNF pathway signaling and ameliorates brain damage after GCI in OVX-rats, which may be closely related to induction of an IL4-mediated anti-inflammatory mechanism. (C) 2018 Elsevier B.V. All rights reserved.