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. 2024 Aug 6;25(16):8560.
doi: 10.3390/ijms25168560.

The Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth Suppress Inflammation in Osteoarthritis

Chuang-Yu Lin  1   2 , Parichart Naruphontjirakul  3 , Te-Yang Huang  4 , Yi-Chia Wu  2   5 , Wei-Hsuan Cheng  6 , Wen-Ta Su  6
Affiliations

The Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth Suppress Inflammation in Osteoarthritis

Chuang-Yu Lin et al. Int J Mol Sci. .

Abstract

Hyaluronic acid injection is commonly used clinically to slow down the development of osteoarthritis (OA). A newly developed therapeutic method is to implant chondrocytes/stem cells to regenerate cartilage in the body. The curative effect of stem cell therapy has been proven to come from the paracrine of stem cells. In this study, exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED) and hyaluronic acid were used individually to evaluate the therapeutic effect in slowing down OA. SHED was cultured in a serum-free medium for three days, and the supernatant was collected and then centrifuged with a speed difference to obtain exosomes containing CD9 and CD63 markers, with an average particle size of 154.1 nm. SW1353 cells were stimulated with IL-1β to produce the inflammatory characteristics of OA and then treated with 40 μg/mL exosomes and hyaluronic acid individually. The results showed that the exosomes successfully inhibited the pro-inflammatory factors, including TNF-α, IL-6, iNOS, NO, COX-2 and PGE2, induced by IL-1β and the degrading enzyme of the extrachondral matrix (MMP-13). Collagen II and ACAN, the main components of the extrachondral matrix, were also increased by 1.76-fold and 2.98-fold, respectively, after treatment, which were similar to that of the normal joints. The effect can be attributed to the partial mediation of SHED exosomes to the NF-κB pathway, and the ability of exosomes to inhibit OA is found not inferior to that of hyaluronic acid.

Keywords: SW1353 cells; exosome; hyaluronic acid; osteoarthritis (OA); stem cells from human exfoliated deciduous teeth (SHED).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Exosome features. (A) The stem cells from human exfoliated deciduous teeth (SHED), scale bar 20 μm. (B) TEM image of purified exosome morphology, scale bar 100 nm. (C) The molecular markers of exosomes. (D) The range of diameters of exosomes. (E) Image of cell morphology of the cell SW1353, scale bar 100 μm.
Figure 2
Figure 2
Cytotoxicity tests. (A) Cytotoxicity test of exosomes against SW1353 cell line. (B) Effect of IL-1β on the survival of SW1353 cell line. (C) Effect of exosomes on inflammatory cell survival. (D) Comparison of survival rates between exosomes and hyaluronic acid treated for 48 h, respectively. Values are expressed as mean ± SD (n = 3), compared with the control group or the first group **: p < 0.01, ***: p < 0.001 and #: p < 0.05, ##: p < 0.01, ###: p < 0.001.
Figure 3
Figure 3
The inflammatory markers TNF-α and IL-6. (A) TNF-α protein expression. (B) Quantification of TNF-α protein expression. (C) IL-6 protein expression. (D) Quantification of IL-6 protein expression. Values are expressed as mean ± SD (n = 3), compared with the first group **: p <0.01 and compared with the second group #: p < 0.05, ##: p < 0.01.
Figure 4
Figure 4
The inflammatory markers iNOS, NO, COX-2 and PGE2. (A) iNOS protein expression. (B) Quantification of iNOS protein expression. (C) Comparison of nitric oxide concentration. (D) Quantification of COX-2 protein expression. (E) Quantification of COX-2 protein expression. (F) Comparison of PGE2 concentration. Values are expressed as mean ± SD (n = 3), compared with first group *: p < 0.05, **: p < 0.01, ***: p < 0.001 and #: p< 0.05, ##: p < 0.01, ###: p < 0.001.
Figure 5
Figure 5
The MMP-13 and ADAMTS5 protein expression. (A) MMP-13 protein expression. (B) Quantification of MMP-13 protein expression. (C) Quantification of MMP-13 mRNA performance. (D) ADAMTS5 protein expression. (E) Quantification of ADAMTS5 protein expression. (F) Quantification of ADAMTS5 mRNA performance. Values are expressed as mean ± SD (n = 3), compared with the first group **: p < 0.01 and #: p< 0.05, ##: p < 0.01, ###: p < 0.001.
Figure 6
Figure 6
The cartilage extracellular matrix. (A) Collagen II protein expression. (B) Quantification of Collagen II protein expression. (C) Quantification of Collagen II mRNA performance. (D) The ACAN protein expression. (E) Quantification of ACAN protein performance. (F) Quantification of ACAN mRNA performance. Values are expressed as mean ± SD (n = 3), compared with first group *: p < 0.05, **: p < 0.01, ***: p < 0.001 and #: p< 0.05, ##: p < 0.01, ###: p < 0.001.
Figure 7
Figure 7
NF-κB gene expression and activity. (A) Quantification of NF-κB mRNA performance. (B) The activity of NF-κB. Values are expressed as mean ± SD (n = 3), compared with first group **: p < 0.01, ***: p < 0.001 and ###: p < 0.001.
Figure 8
Figure 8
Schematic diagram illustrating the inhibition of the OA pathway by SHED exosomes.
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