Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression.

In contrast, in the aged group, M1 number showed an increasing trend during the observation period ( p values for main effects of post-surgery time and mouse age and their interaction: 0.0046, 0.0299, and 0.0020, respectively; two-way factorial ANOVA), resulting in significantly higher M1 number on day 7 ( p value: 0.0047; Tukey’s post-hoc test) ( Figure 2 a and Supplementary Table S1 ).

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Interestingly, the suppressive effects on the gene expression of inflammatory cytokines and Nf-κb and the enhancing effects on the M2-related genes in M1 showed significant ( Il-6 , iNos , Ym-1 , Fizz-1 ) or marginally significant ( Tnf-α , Nf-κb ) reduction when supernatants from aged MSCs were used (mean relative expression levels in M1 with young vs. aged MSCs and p values: Il-6 [1.01 vs. 2.16, 0.0091], iNos [0.50 vs. 1.11, 0.0308], Tnf-α [0.57 vs. 0.76, 0.0466], Nf-κb [0.15 vs. 0.65, 0.0409], Arg-1 [2.67 vs. 2.39, 0.1322], Ym-1 [3.46 vs. 2.26, 0.0014], and Fizz-1 [4.81 vs. 2.62, 0.0093]; Tukey’s post-hoc test) ( Figure 5 d–f and Supplementary Table S2 ). 2.6.

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Recent studies have suggested that the crosstalk between these cells may be significant for tissue regeneration [ 23 , 24 , 25 ].

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