Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton’s jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease.

Atopic dermatitis (AD) is an inflammatory disease that typically begins in childhood and may persist into adulthood, becoming a lifelong condition. The major inflammatory mediators of AD are known to be interleukin IL4 and IL13, so Dupilumab, which is able to inhibit both interleukins by blocking the shared IL4Rα subunit, has become an attractive option for treating AD. Mesenchymal stem cells (MSCs) are involved in the onset and development of AD by secreting specific interleukins. The aim of this study was to isolate MSCs from healthy controls (C-MSCs) and patients with AD before (AD-MSCs T0) and after 16 weeks of treatment with Dupilumab (AD-MSCs T16); to evaluate the expression mainly of IL4 and IL13 and of other inflammatory cytokines in C-MSCs, AD-MSCs at T0 and at T16; and to evaluate the efficacy of Dupilumab on MSCs immunobiology. C- and AD-MSCs (T0, T16) were isolated from skin specimens and characterized; the expression/secretion of IL4 and IL13 was evaluated using immuno-cytochemistry (ICC), indirect immune-fluorescence (IIF) and an ELISA test; secretion of IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, Interferon gamma (IFNγ), Tumor necrosis factor alpha (TNFα), Granulocyte Colony-Stimulating Factor (G-CSF), and Transforming Growth Factor beta1 (TGFβ1) were measured with ELISA. IL13 and IL6 were over-expressed, while IL4 was down-regulated in AD-MSCs at T0 compared to C-MSCs. IL6 and IL13 expression was restored after 16 weeks of Dupilumab treatment, while no significant effects on IL4 expression were noted. Finally, IL2, IL5, IL10, IL12, IL17A, INFγ, TNFα, G-CSF, and TGFβ1 were similarly secreted by C- and AD-MSCs. Although Dupilumab blocks the IL4Rα subunit shared by IL4 and IL13, it is evident that its real target is IL13, and its ability to target IL13 in MSCs reinforces the evidence, already known in differentiated cells, of the central role IL13 rather than IL4 in the development of AD. The inflammatory cascade in AD begins at the mesenchymal level, so an upstream therapeutic intervention, able to modify the immunobiology of atopic MSCs, could potentially change the natural history of the disease.

Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number “CRD42023420245”. According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on–off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.

The role of 11β-HSD1 in Alzheimer’s disease (AD) has garnered significant attention due to its involvement in glucocorticoid metabolism, neuroinflammation, and cognitive decline. This review explores the current understanding of 11β-HSD1 in AD, examining genetic, preclinical, and clinical research. Genetic studies have identified 11β-HSD1 polymorphisms that may influence AD risk, although findings remain inconsistent. Mechanistically, 11β-HSD1 promotes neurodegeneration through the dysregulation of glucocorticoid activity, contributing to hippocampal atrophy, amyloid plaque formation, and tau pathology. Preclinical studies have shown that 11β-HSD1 inhibitors offer neuroprotective effects, including enhanced cognitive function, reduced inflammation, and improved mitochondrial activity. However, clinical trials, including those involving ABT-384 and Xanamem, have produced mixed results, with no substantial cognitive improvements despite effective enzyme inhibition. These inconsistencies highlight the complexity of AD and the challenges in translating preclinical findings into clinical outcomes. Moreover, while 11β-HSD1 inhibition holds therapeutic potential, other strategies targeting neuroinflammation, autophagy, and glucocorticoid signaling are also being explored. Ongoing research is focusing on optimizing 11β-HSD1 inhibitors, identifying biomarkers for patient selection, and investigating combination therapies to enhance treatment efficacy. Ultimately, 11β-HSD1’s role in AD presents a promising therapeutic target, but further studies are required to fully understand its potential in managing the disease.

Polydatin is a polyphenol, whose beneficial properties, including anti-inflammatory and antioxidant activity, have been largely demonstrated. At the same time, copper has an important role in the correct organism homeostasis and alteration of its concentration can induce oxidative stress. In this study, the efficacy of polydatin to counteract the stress induced by CuSO₄ exposure or by caudal fin amputation was investigated in zebrafish larvae. The study revealed that polydatin can reduced the stress induced by a 2 h exposure to 10 µM CuSO₄ by lowering the levels of il1b and cxcl8b.1 and reducing neutrophils migration in the head and along the lateral line. Similarly, polydatin administration reduced the number of neutrophils in the area of fin cut. In addition, polydatin upregulates the expression of sod1 mRNA and CAT activity, both involved in the antioxidant response. Most of the results obtained in this study support the working hypothesis that polydatin administration can modulate stress response and its action is more effective in mitigating the effects rather than in preventing chemical damages.

The aetiology of leiomyoma is debated; however, dysregulated progenitor cells or miRNAs appear to be involved. Previous profiling analysis of miRNA in healthy myometrium- (M-MSCs) and leiomyoma- (L-MSCs) derived mesenchymal stem cells (MSCs) identified 15 miRNAs differentially expressed between M-MSCs and L-MSCs. Here, we try to elucidate whether these differentially regulated 15 miRNAs arise as a conversion of M-MSCs along the differentiation process or whether they may originate from divergent cell commitment. To trace the origin of the dysregulation, a comparison was made of the expression of miRNAs previously identified as differentially regulated in M-MSCs and L-MSCs with that detected in MSCs from amniotic fluid (considered as a substitute for embryonic cells). The results do not allow for a foregone conclusion: the miRNAs converging to the adherens junction pathway showed a gradual change along the differentiation process, and the miRNAs which coincided with the other three pathways (ECM-receptor interaction, TGFβ and cell cycle) showed a complex, not linear, regulation and, therefore, a trend along the hypothetical differentiation process was not deduced. However, the role of miRNAs appears to be predominant in the onset of leiomyoma and may follow two different mechanisms (early commitment; exacerbation); furthermore, miRNAs can support the observed (epigenetic) predisposition.