Diabetes mellitus (DM) is an alarming metabolic disease in which insulin secreting β-cells are damaged to various extent. Unfortunately, although currently available treatments help to manage the disease, however, patients usually develop complications, as well as decreased life quality and increased mortality. Thus, efficient therapeutic interventions to treat diabetes are urgently warranted. During the past years, mesenchymal stem cells (MSCs) have made their mark as a potential weapon in various regenerative medicine applications. The main fascination about MSCs lies in their potential to exert reparative effects on an amazingly wide spectrum of tissue injury. This is further reinforced by their ease of isolation and large ex vivo expansion capacity, as well as demonstrated multipotency and immunomodulatory activities. Among all the sources of MSCs, those isolated from umbilical cord-Wharton’s jelly (WJ-MSCs), have been proved to provide a great source of MSCs. WJ-MSCs do not impose any ethical concerns as those which exist regarding ESCs, and represent a readily available non-invasive source, and hence suggested to become the new gold standard for MSC-based therapies. In the current review, we shall overview achievements, as well as challenges/hurdles which are standing in the way to utilize WJ-MSCs as a novel efficient therapeutic modality for DM.

Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21–Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes.SIGNIFICANCE STATEMENTMolecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21–Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development.

Osteoarthritis (OA) is a prevalent progressive disease that frequently coexists with obesity. For several decades, OA was thought to be the result of ageing and mechanical stress on cartilage. Researchers’ perspective has been greatly transformed when cumulative findings emphasized the role of adipose tissue in the diseases. Nowadays, the metabolic effect of obesity on cartilage tissue has become an integral part of obesity research; hoping to discover a disease-modifying drug for OA. Recently, several adipokines have been reported to be associated with OA. Particularly, metrnl (meteorin-like) and retinol-binding protein 4 (RBP4) have been recognized as emerging adipokines that can mediate OA pathogenesis. Accordingly, in this review, we will summarize the latest findings concerned with the metabolic contribution of obesity in OA pathogenesis, with particular emphasis on dyslipidemia, insulin resistance and adipokines. Additionally, we will discuss the most recent adipokines that have been reported to play a role in this context. Careful consideration of these molecular mechanisms interrelated with obesity and OA will undoubtedly unveil new avenues for OA treatment.