Wnt signaling plays important roles in stem cell self-renewal and differentiation in adults as well as in embryonic development. Mutations that activate canonical Wnt/β-catenin signaling also initiate and maintain several cancer states, including colorectal cancer and leukemia, and hence Wnt inhibitors are currently being explored as therapeutic options. In this review, we summarize previous studies and update recent findings on canonical Wnt signaling and its components, as well as their roles in somatic stem cell homeostasis and maintenance of cancer initiating cells.

ALDH has been shown to be a marker that denotes a sub-population of cancer stem cells in colorectal and other cancers. This sub-population of cells shows an increased risk for tumor initiation, metastasis, and resistance to chemotherapy and radiation resulting in recurrence and death. It is thus essential to identify the important signaling pathways related to ALDH1+ CSCs in colon cancer. The essential issue becomes to isolate pure sub-populations of cells from heterogeneous tissues for further analysis. To achieve this goal, tissues from colorectal cancer Stage III patients were immuno-stained with ALDH1 antibody. Target ALDH1+ and ALDH1- cells from the same tissue were micro-dissected using Laser Capture Microdissection (LCM). Captured cells were lysed and analyzed using LC-MS/MS where around 20,000 cells were available for analysis. This analysis resulted in 134 proteins which were differentially expressed between ALDH1+ and ALDH1- cells in three patient sample pairs. Based on these differentially expressed proteins an IPA pathway analysis was performed that showed two key pathways in cell to cell signaling and organismal injury and abnormalities. The IPA analysis revealed β-catenin, NFκB (p65) and TGFβ1 as important cancer-related proteins in these pathways. A TMA validation using immunofluorescence staining of tissue micro-arrays including 170 cases was used to verify that these key proteins were highly overexpressed in ALDH1+ cells in colon cancer tissues compared to ALDH1- cells.

Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a pleiotropic protein associated with numerous cell functions, including transcription and differentiation. The role of CITED2 has been investigated in a number of malignancies; however, the roles of this protein in gastric cancers remain unclear. Therefore, we determined the role of CITED2 in gastric cancers.

Because space missions produce pathophysiological alterations such as cardiovascular disorders and bone demineralization which are very common on Earth, biomedical research in space is a frontier that holds important promises not only to counterbalance space-associated disorders in astronauts but also to ameliorate the health of Earth-bound population. Experiments in space are complex to design. Cells must be cultured in closed cell culture systems (from now defined experimental units (EUs)), which are biocompatible, functional, safe to minimize any potential hazard to the crew, and with a high degree of automation. Therefore, to perform experiments in orbit, it is relevant to know how closely culture in the EUs reflects cellular behavior under normal growth conditions. We compared the performances in these units of three different human cell types, which were recently space flown, i.e. bone mesenchymal stem cells, micro- and macrovascular endothelial cells. Endothelial cells are only slightly and transiently affected by culture in the EUs, whereas these devices accelerate mesenchymal stem cell reprogramming toward osteogenic differentiation, in part by increasing the amounts of reactive oxygen species. We conclude that cell culture conditions in the EUs do not exactly mimic what happens in a culture dish and that more efforts are necessary to optimize these devices for biomedical experiments in space. Impact statement Cell cultures represent valuable preclinical models to decipher pathogenic circuitries. This is true also for biomedical research in space. A lot has been learnt about cell adaptation and reaction from the experiments performed on many different cell types flown to space. Obviously, cell culture in space has to meet specific requirements for the safety of the crew and to comply with the unique environmental challenges. For these reasons, specific devices for cell culture in space have been developed. It is important to clarify whether these alternative culture systems impact on cell performances to allow a correct interpretation of the data.

Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

We have previously reported that human neonatal foreskin stromal cells (hNSSCs) promote angiogenesis in vitro and in chick embryo chorioallantoic membrane (CAM) assay in vivo. To examine the in vivo relevance of this observation, we examined in the present study the differentiation potential of hNSSCs in ex vivo organotypic cultures of embryonic chick femurs. Isolated embryonic chick femurs (E10 and E11) were cultured for 10 days together with micro-mass cell pellets of hNSSCs, human umbilical vein endothelial cells (HUVEC) or a combination of the two cell types. Changes in femurs gross morphology and integration of the cells within the femurs were investigated using standard histology and immunohistochemistry. After 10 days, the femurs that were cultured in the presence of hNSSCs alone or hNSSC + HUVEC cells grew longer, exhibited thicker diaphysis and an enlarged epiphyseal region compared to control femurs cultured in the absence of cells. Analysis of cell-femur interactions, revealed intense staining for CD31 and enhanced deposition of collagen rich matrix along the periosteum in femurs cultured with hNSSCs alone or hNSSCs + HUVEC and the most pronounced effects were observed in hNSSC + HUVEC cultures. Our data suggest that organotypic cultures can be employed to test the differentiation potential of stem cells and demonstrate the importance of stem cell interaction with 3D-intact tissue microenvironment for their differentiation.

The first case of plasma cell leukemia (PCL) was recognized by Gluzinski and Reichentein. It is the most aggressive among the monoclonal gammopathies. It is diagnosed by the presence of more than 20% plasma cells in the peripheral blood or an absolute plasma cell count of> 2000/mm3. Because of the relatively low incidence, most data come from case reports and retrospective studies. No prospective series have been published, and only seven reports including more than twenty patients have been identified. We report a retrospective series of 18 patients identified as PCL.

Thia study evaluates the effects of Ailanthus excelsa Roxb methanolic extract (AER-ME) in rats induced with Myocardial Infarction (MI) followed by transplantation of MSCs.

Neutrophils produce and carry key components of the alternative pathway (AP) of complement, including properdin (P). The effect of chemotherapy-induced absolute neutropenia on circulating P levels and AP function has not been previously established.

Effective regenerative treatments for periodontal tissue defects have recently been demonstrated using mesenchymal stromal/stem cells (MSCs). Furthermore, current bioengineering techniques have enabled de novo fabrication of tooth-perio dental units in mice. These cutting-edge technologies are expected to address unmet needs within regenerative dentistry. However, to achieve efficient and stable treatment outcomes, preparation of an appropriate stem cell source is essential. Many researchers are investigating the use of adult stem cells for regenerative dentistry; bone marrow-derived MSCs (BM-MSCs) are particularly promising and presently used clinically. However, current BM-MSC isolation techniques result in a heterogeneous, non-reproducible cell population because of a lack of identified distinct BM-MSC surface markers. Recently, specific subsets of cell surface markers for BM-MSCs have been reported in mice (PDGFRα+ and Sca-1+) and humans (LNGFR+, THY-1+ and VCAM-1+), facilitating the isolation of unique enriched BM-MSCs (so-called "purified MSCs"). Notably, the enriched BM-MSC population contains neural crest-derived cells, which can differentiate into cells of neural crest- and mesenchymal lineages. In this review, characteristics of the enriched BM-MSCs are outlined with a focus on their potential application within future regenerative dentistry.

Nucleostemin (NS)/GNL3 protein has been recently documented to be a nucleolar protein that was abundantly expressed in stem cells and cancer cells. Herein, we showed that NS was upregulated in HCC tissues and the expression of NS was inversely correlated with that of p53. Overexpression of NS predicted significantly worsened prognosis in HCC patients, suggesting that NS might serve as a prognostic marker of HCC. In addition, we found that depletion of NS sensitized HCC cells to sorafenib-induced apoptosis. Moreover, we found that the mechanism underlying NS-mediated sorafenib resistance involved dysregulated expression of p53, and downstream Bax and Bcl-2 proteins. NS interacted with p53 in HCC cells. Depletion of NS increased the expression of p53 and Bax, whereas impaired the level of cellular Bcl-2. Interference of NS enhanced the cytotoxic effects of sorafenib in HCC cells. Furthermore, ectopic expression of NS impaired the apoptosis of HCC cells following sorafenib exposure. Therefore, NS may contribute to sorafenib resistance in HCC cells through the modulation of p53 pathway and Bcl-2 proteins. These findings indicated that the combination of silencing NS expression and sorafenib treatment is a promising therapeutic strategy in treatment of HCC.

Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients.

Recently, supramolecular hydrogels assembled through nonspecific interactions between polymers and nanoparticles (termed PNP systems) were reported to have rapid shear-thinning and self-healing properties amenable for cell-delivery applications in regenerative medicine. Here, we introduce protein engineering concepts into the design of a new family of PNP hydrogels to enable direct control over the polymer-nanoparticle interactions using peptide-based molecular recognition motifs. Specifically, we have designed a bifunctional peptide that induces supramolecular hydrogel assembly between hydroxy apatite nanoparticles and an engineered, recombinant protein. We demonstrate that this supramolecular assembly critically requires molecular recognition, as no assembly is observed in the presence of control peptides with a scrambled amino acid sequence. Titration of the bifunctional peptide enables direct control over the number of physical cross-links within the system and hence the resulting hydrogel mechanical properties. As with previous PNP systems, these materials are rapidly shear-thinning and self-healing. As proof-of-concept, we demonstrate that these materials are suitable for therapeutic cell delivery applications in a preclinical murine calvarial defect model.

Administration of ex vivo-expanded human bone marrow-derived mesenchymal stromal cells (hBMMSC) obtained from single donors has shown therapeutic benefits in both preclinical and clinical studies. In this study, the safety, toxicity and biodistribution profiles of a pooled hBMMSC population, produced from three healthy donors were assessed in rodent and non-rodents.

Human embryonic stem cell (hESC) lines are commonly maintained on inactivated feeder cells, in the medium supplemented with basic fibroblast growth factor (bFGF). However, limited availability of feeder cells in culture, and the high cost of growth factors limit their use in scalable expansion of hESC cultures for clinical application. Here, we describe an efficient and cost-effective feeder and bFGF-free culture of hESCs using conditioned medium (CM) from immortalized feeder cells.

Human bone marrow is rich in various growth factors which may support the chondrocyte growth. This study was conducted to compare the culture characteristics of human growth plate chondrocyte in foetal bovine serum (FBS) and human autologous bone marrow extract (BME) in monolayer culture.

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use neurogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.

COX-2 overexpression is associated with several hallmarks of carcinogenesis such as proliferation, angiogenesis, invasion and metastasis. Fifty cases of canine mast cell tumours (MCT) were retrospectively evaluated and submitted to immunohistochemistry for COX-2, CD31, Ki-67, MAC-387 and CD3. Furthermore its relationship with clinicopathological variables and overall survival (OS) was analysed. COX-2 intensity (P = 0.016), but not COX-2 extension nor score was associated with decreased OS and higher grades of malignancy according to Patnaik (P = 0.002) and Kiupel (P < 0.001) grading systems. Cox-2 intensity was also associated with higher Ki-67 scores (P = 0.009), higher mitotic index (P = 0.022) and higher microvascularization density (P = 0.045). No association was observed for COX-2 intensity and CD3-T lymphocyte (P = 0.377) and macrophage infiltration (P = 0.261) by MAC-387 immunollabelling, suggesting an active role of COX-2 in MCT oncogenesis mainly through proliferation and angiogenesis stimulation making it a potentially clinical relevant prognosis marker and therapeutic target.

Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, and as a consequence, by decreased dopamine levels in the striatum. Currently available therapies are not able to stop or reverse the progression of the disease. A novel therapeutic approach is based on cell therapy with stem cells, in order to replace degenerated neurons. Among stem cells, mesenchymal stem cells seemed the most promising thanks to their capacities to differentiate toward dopaminergic neurons and to release neurotrophic factors. Indeed, mesenchymal stem cells are able to produce different molecules with immunomodulatory, neuroprotective, angiogenic, chemotactic effects and that stimulate differentiation of resident stem cells. Mesenchymal stem cells were isolated for the first time from bone marrow, but can be collected also from adipose tissue, umbilical cord and other tissues. In this review, we focused our attention on mesenchymal stem cells derived from different sources and their application in Parkinson's disease animal models.