Current Issue : October - December Volume : 2012 Issue Number : 4 Articles : 7 Articles
Transforming growth factor beta (TGF-�Ÿ) signaling has been implicated in driving tumor progression and\r\nmetastasis by inducing stem cell-like features in some human cancer cell lines. In this study, we have utilized a novel\r\nmurine cell line NMuMG-ST, which acquired cancer stem cell (CSC) phenotypes during spontaneous transformation\r\nof the untransformed murine mammary cell line NMuMG, to investigate the role of autocrine TGF-�Ÿ signaling in\r\nregulating their survival, metastatic ability, and the maintenance of cancer stem cell characteristics. We have\r\nretrovirally transduced a dominant-negative TGF-�Ÿ type II receptor (DNRII) into the NMuMG-ST cell to abrogate\r\nautocrine TGF-�Ÿ signaling. The expression of DNRII reduced TGF-�Ÿ sensitivity of the NMuMG-ST cells in various\r\ncell-based assays. The blockade of autocrine TGF-�Ÿ signaling reduced the ability of the cell to grow anchorage-\r\nindependently and to resist serum deprivation-induced apoptosis. These phenotypes were associated with reduced\r\nlevels of active and phosphorylated AKT and ERK, and Gli1 expression suggesting that these pathways contribute\r\nto the growth and survival of this model system. More interestingly, the abrogation of autocrine TGF-�Ÿ signaling also\r\nled to the attenuation of several features associated with mammary stem cells including epithelial-mesenchymal\r\ntransition, mammosphere formation, and expression of stem cell markers. When xenografted in athymic nude mice,\r\nthe DNRII cells were also found to undergo apoptosis and induced significantly lower lung metastasis burden than\r\nthe control cells even though they formed similar size of xenograft tumors. Thus, our results indicate that autocrine\r\nTGF-�Ÿ signaling is involved in the maintenance and survival of stem-like cell population resulting in the enhanced\r\nmetastatic ability of the murine breast cancer cells....
The need for a consistent therapeutic approach to tendon injury repair is long overdue. Patients with tendon microtears or full\r\nruptures are eligible for a wide range of invasive and non invasive interventions, often subjectively decided by the physician. Surgery\r\nproduces the best outcomes, and while studies have been conducted to optimize graft constructs and to track outcomes, the data\r\nfrom these studies have been inconclusive on the whole. What has been established is a clear understanding of healthy tendon\r\narchitecture and the inherent process of healing.With this knowledge, tissue regeneration efforts have achieved immense progress\r\nin scaffold design, cell line selection, and, more recently, the appropriate use of cytokines and growth factors. This paper evaluates\r\nthe plasticity of bone-marrow-derived stem cells and the elasticity of recently developed biomaterials towards tendon regeneration\r\nefforts. Mesenchymal stem cells (MSCs), hematopoietic progenitor cells, and poly(1,8-octanediol co-citrate) scaffolds (POC) are\r\ndiscussed in the context of established grafting strategies. With POC scaffolds to cradle the growth of MSCs and hematopoietic\r\nprogenitor cells, developing a fibroelastic network guided by cytokines and growth factors may contribute towards consistent graft\r\nconstructs, enhanced functionality, and better patient outcomes....
Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs) persist after birth in the superficial nerve sheath\r\nof peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed\r\non the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of\r\nmelanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and\r\na very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self-renewal, expansion\r\nand differentiation are reviewed. A model is presented to show how the detrimental effects of long-term UVA/UVB radiation on\r\nDNA and repair mechanisms in MSCs convert them to melanoma stem cells. Zebrafish have many advantages for investigating\r\nthe role of MSCs in the development of melanoma. The signaling pathways regulating the development of MSCs in zebrafish are\r\nvery similar to those found in humans and mice. The ability to easily manipulate the MSC population makes zebrafish an excellent\r\nmodel for studying how damage to MSCs may lead to melanoma....
Poor peripheral blood stem cell (PBSC) mobilization predicts worse outcome for myeloma and lymphoma patients post\r\nautologous stem cell transplant (ASCT). We hypothesize that PBSC harvest using plerixafor and G-CSF in poor mobilizers may\r\nimprove long-termoutcome.We retrospectively analyzed the data on patients who had second PBSC mobilization using plerixafor\r\nand G-CSF as a rescue. Nine lymphoma and 8 multiple myeloma (MM) patients received the drug. A control group of 25MMand\r\nlymphoma patients who were good mobilizers with G-CSF only was used for comparison. Sixteen of the 17 poor mobilizers\r\nproceeded to ASCT, and one MM patient had tandem transplants. Length of hospital stay, infection incidence, granulocyte\r\nengraftment, and long-term hematopoietic recovery were not significantly different between the two groups. In conclusion, all\r\npoor mobilizers were able to obtain adequate stem cells transplant dose and had similar transplant course and long-term outcome\r\nto that of the control good mobilizers group....
Skeletal myogenesis is an intricate process coordinated temporally by multiple myogenic regulatory factors (MRF) including Myf5, which is the first MRF expressed and marks the commitment of skeletal muscle lineage. The expression of Myf5 gene during early embryogenesis is controlled by a set of enhancer elements, and requires the histone acetyltransferase (HAT) activity of transcriptional coactivator p300. However, it is unclear as to how different regulatory signals converge at enhancer elements to regulate early Myf5 gene expression, and if p300 is directly involved. We show here that p300 associates with the Myf5 early enhancer at the early stage of stem cell differentiation, and its HAT activity is important for the recruitment of �Ÿ-catenin to this early enhancer. In addition, histone H3-K27 acetylation, but not H3-K9/14, is intimately connected to the p300 HAT activity. Thus, p300 is directly involved in the regulation of the Myf5 early enhancer, and is important for specific histone acetylation and transcription factor recruitment. This connection of p300 HAT activity with H3-K27 acetylation and �Ÿ-catenin signalling during myogenic differentiation in vitro offers a molecular insight into the enhancer-elements participation observed in embryonic development. In addition, pluripotent stem cell differentiation is a valuable system to dissect the signal-dependent regulation of specific enhancer element during cell fate determinations....
The a-chemokine stromal derived factor 1 (SDF-1), which binds to the CXCR4 and CXCR7 receptors, directs migration and\r\nhoming of CXCR4 hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) and plays a crucial role in retention of\r\nthese cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting\r\nSDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive\r\nlipids, such as sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), and migrate in response to gradients of certain\r\nextracellular nucleotides, including uridine triphosphate (UTP) and adenosine triphosphate (ATP). Moreover, the responsiveness\r\nof HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments\r\nand antimicrobial cationic peptides, such as cathelicidin/LL-37 or �Ÿ2-defensin) as well as prostaglandin E2 (PGE2). Since all these\r\nfactors are upregulated in BM aftermyeloblative conditioning for transplantation, a more complex picture of homing emerges that\r\ninvolves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis....
Stem cells have the significant latent to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can multiply without limit to replenish other cells as long as the person is alive. When a stem cell multiplies, every new cell has the latent to either remain a stem cell or become another type of cell with a more dedicated function, such as a brain cell or a red blood cell. Research on stem cells is advancing information about how an organism develops from a single cell and how healthy cells substitute damaged cells in adult organisms. This promising area of science leading scientists to explore the possibility of cell-based therapies to treat diseases, which referred as regenerative or reparative medicine. The vast opportunity in medicine is regenerative medicine wherein stem cell therapy is going to play a major role. This review highlights the stem cell therapies that have potential to cure numerous life threatening diseases as well future perspectives in the area of stem cell research....
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