Pituitary adenomas, stem cells, and cancer stem cells: what's new?

PURPOSE: To clarify the existence of pituitary stem cells (SCs) both in the embryonic and the postnatal gland and the role for SCs in pituitary adenomas. METHODS: This work, which does not address the pathogenesis of pituitary adenomas, reviews the latest research findings and discoveries on SCs in pituitary and cancer SCs (CSCs) in pituitary adenomas and discusses the involvement of the EMT. RESULTS: Several groups using different approaches and techniques have demonstrated the existence of SCs and CSCs and as they are major players in pituitary adenoma onset. CONCLUSIONS: As in other benign and malignant tumors, the hypothesis that CSCs play a pivotal role in pituitary adenoma onset has been confirmed as well as the existence of a link between the epithelial-to-mesenchymal transition (EMT) process and CSC formation in epithelial tumors.

T helper (Th)1, Th17 and Th2 imbalance in mesenchymal stem cells of adult patients with atopic dermatitis: at the origin of the problem.

BACKGROUND: Atopic dermatitis (AD) is a chronic and inflammatory disease characterized by a marked imbalance of T helper (Th)2 vs. Th1/Th17 cells in the early phase of AD, whereas a mixed Th1/Th2 pattern of inflammation is usually found at the chronic stage. These features have not been extensively evaluated in undifferentiated skin cells of patients affected by AD. OBJECTIVES: To evaluate the relative expression of 22 genes encoding Th1, Th2 and Th17 cytokines and the secretion of the corresponding proteins in cutaneous mesenchymal stem cells (MSCs) isolated from skin of patients with AD (AD-MSCs) and their role in AD onset. METHODS: AD-MSCs were isolated, characterized and profiled by polymerase chain reaction array and enzyme-linked immunosorbent assay for the relative expression and secretion of cytokines involved in the Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy people were used as controls (C-MSCs). RESULTS: AD-MSCs showed an upregulation of many Th1/Th17 cytokines [interleukin (IL)-6, IL-8, IL-12, IL-13, IL-17A, IL-17F, transforming growth factor-ß, interferon-γ], while Th2 chemokines (IL-2, IL-4, IL-5, IL-23A) were downregulated in AD-MSCs. Finally, some genes/proteins (CCL1, IL-17C, tumour necrosis factor-α) did not show variations between C-MSCs and AD-MSCs. CONCLUSIONS: The profile of MSCs obtained from patients with chronic AD retraces the Th1/Th17 cell environment observed in differentiated cells of chronic AD. This evidence could open a new scenario in the pathogenesis of AD, according to which the inflammatory process may involve MSCs early on.

New miRNAs network in human mesenchymal stem cells derived from skin and amniotic fluid.

Mesenchymal stem cells (MSCs), isolated from different adult sources, have great appeal for therapeutic applications due to their simple isolation, extensive expansion potential, and high differentiative potential.In our previous studies we isolated MSCs form amniotic fluid (AF-MSCs) and skin (S-MSCs) and characterized them according to their phenotype, pluripotency, and mRNA/microRNAs (miRNAs) profiling using Card A from Life Technologies.Here, we enlarge the profiling of AF-MCSs and S-MSCs to the more recently discovered miRNAs (Card B by Life Technologies) to identify the miRNAs putative target genes and the relative signaling pathways. Card B, in fact, contains miRNAs whose role and target are not yet elucidated.The expression of the analyzed miRNAs is changing between S-MSCs and AF-MSCs, indicating that these two types of MSCs show differences potentially related to their source. Interestingly, the pathways targeted by the miRNAS deriving from Card B are the same found during the analysis of miRNAs from Card A.This result confirms the key role played by WNT and TGF-ß pathways in stem cell fate, underlining as other miRNAs partially ignored up to now deserve to be reconsidered. In addition, this analysis allows including Adherens junction pathways among the mechanisms finely regulated in stem cell behavior.