Background: It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results: In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC). Cells were treated with: (1) TPA, forskolin, IBMX, FGF-1 or (2) retinoic acid and 2-mercaptoethanol (BME). Treatment (1) induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1) compared with treatment (2). In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion: Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.

Background/Objectives: Ustekinumab, targeting the shared p40 subunit of interleukin (IL)-12 and IL-23, is an effective therapy for Crohn’s disease (CD), yet reliable predictors of response remain lacking. Given the central role of the IL-12/IL-23 axis in intestinal inflammation, we aimed to characterize the baseline mucosal expression of IL-12/IL-23 pathway components in lamina propria immune cells, and to explore their association with clinical response and remission following ustekinumab therapy. Methods: In this prospective, single-center study, biopsy-derived lamina propria mononuclear cells (LPMCs) were obtained from patients with CD prior to ustekinumab initiation. Gene expression of IL-12/IL-23 cytokine subunits and receptors was assessed by quantitative real-time PCR. Flow cytometry was performed to evaluate the distribution of T helper and innate lymphoid cell subsets and the expression of IL-23R and IL-12Rβ2. Clinical outcomes were assessed at week 16. Results: Fifteen consecutive patients were enrolled and included in the study. At week 16, 14/15 (93.3%) and 9/15 (60.0%) of patients reached clinical response and remission, respectively. No statistically significant differences in baseline mucosal gene expression of IL-12/IL-23 pathway components were observed between remitters and non-remitters. A trend toward higher expression of receptor subunits (IL23R, IL12RB1, IL12RB2) was observed in remitters, albeit with high variability and overlapping distributions. Similarly, cytokine subunits (IL23p19, IL12/IL23p40, IL12p35) showed no consistent differential expression pattern between the groups. In contrast, flow cytometry revealed a significantly higher frequency of IL-23R-expressing Th1 cells in remitters compared with non-remitters (20.6% vs. 6.8%, p = 0.009). Conclusions: Baseline transcriptional profiling of IL-12/IL-23 pathway components was not associated with remission following ustekinumab therapy. However, increased expression of IL-23R on mucosal Th1 cells identified a distinct immunological signature associated with clinical remission, suggesting that IL-23R expression on mucosal Th1 cells may represent a promising candidate biomarker that requires validation in larger independent cohorts.