Abstract
Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Highlights
Periodontitis is polymicrobe-induced inflammatory condition that damages the tooth-supporting tissues, including the cementum, alveolar bone, gingiva and periodontal ligament.[1]
Characterization of 2D- and 3D-exos dental pulp stem cells (DPSCs) formed multicellular spheroids in the 3D culture system, distinct from the spindle-like morphology of 2D-cultured DPSCs, which indicates that our 3D cell culture models were successfully
Transmission electron microscopy (TEM) that the 3D-exo-treated groups displayed the infiltration of revealed that the 2D- and 3D-exos were nanosized vesicles with a fewer immune cells into the colon lamina propria, a lower bilayer membrane (Fig. 1b)
Summary
Yong Zhang[1], Jiayao Chen 1, Haijun Fu1, Shuhong Kuang[1], Feng He2, Min Zhang[3,4], Zongshan Shen[1], Wei Qin[1], Zhengmei Lin1 ✉ and Shuheng Huang1 ✉. Multiple researchers have found that exosomes released from MSCs from different sources can differentially alleviate periodontitis and promote periodontal regeneration.[17] Among all sources of MSCs, dental pulp stem cells (DPSCs) have attracted particular attention because relative to BMSCs, they are readily accessible, less tumorigenic and demonstrate increased osteogenic and proliferative activity, showing greater capacity for the treatment of periodontitis.[18,19,20] In this context, we have conducted a number of studies to expand the understanding of DPSCs and facilitate their clinical application.[21,22,23,24] Recently, our group reported that dental pulp stem cellderived exosomes (DPSC-exos) can accelerate alveolar bone healing by transferring miR-1246 to immune cells in the periodontium, which can suppress inflammatory and immune responses.[25] DPSC-exos show therapeutic potential for many diseases, their low yield limits their therapeutic application.[26,27] The yield of exosomes is affected by the culture system, isolation method and purification process employed.[26,27]. Shortening of the colon indicates the aggravation of intestinal inflammation.50 3D-exo-treated
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