Transplantation of dental tissue-derived mesenchymal stem cells ameliorates nephritis in lupus mice

Xiaojun Tang, Wenchao Li, Xin Wen, Zhuoya Zhang, Weiwei Chen, Genhong Yao, Hongwei Chen, Dandan Wang, Songtao Shi, Lingyun Sun


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® 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+IFNγ+) cells and plasma (B220CD138+) 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.