Fig. 3: CSF immunological and proteomic profile.

PCA of the detectable CSF analytes evaluated at baseline (yellow) and 3 months after (green) transplantation in the low-dose (n.6) (a) and high-dose (n.6) (b) groups. a, In the low-dose group, the first two principal components, PC1 and PC2, explained 30.1% and 19.9% of the variation, respectively. b, In the high-dose group, PC1 and PC2, explained 32.5% and 18.9% of the variation, respectively, with a clear distinction between baseline and 3-month follow-up samples. c, Heat map representing the fold change (red, upregulation; blue, downregulation) of CSF analyte (y axis) between baseline and 3-month follow-up for each patient (x axis). Differences in the expression of each analyte were calculated by a non-parametric exact two-sided Wilcoxon test. * indicates statistically significant difference (exact P < 0.05). d,e, Pathway enrichment analysis on CSF differentially expressed proteins after transplantation in the ‘low-dose’ (d) and ‘high-dose’ groups (e). Dot plots of enriched Reactome (REAC) pathways and Gene Ontology (GO) terms (REAC in green labels, GO:BP in black labels and GO:CC in red labels) of biological interest selected among the top enriched terms (FDR < 0.05). The x axis represents the ‘rich factor’ (gene ratio) of each term. The dots’ size and color represent the gene number (intersection size) and the adjusted P value (−log₁₀[P value adj.]), respectively. f,g, Curves of pre-ranked GSEA for selected datasets, showing the profile of the running enrichment score (ES) and positions of gene set members on the rank-ordered list. The GSEA curves of neutrophil degranulation, immune system and innate immune system pathways show a trend for a negative enrichment in the low-dose group (f). In the high-dose group, the GSEA curves of nervous system development pathway, and neurogenesis and cell migration GO terms show significant positive enrichment (g). Comparisons were performed using a two-sided paired Studentʼs t-test. Significance levels were adjusted with the Benjamini–Hochberg multi-test correction. h,i, Chord plots of enriched pathways of biological interest, selected among the top 20 enriched, in the low-dose (h) and high-dose (i) groups.