Toward osteogenic differentiation of marrow stromal cells and in vitro production of mineralized extracellular matrix onto natural scaffolds

Uncorrected proofTissue engineering has emerged as a new interdisciplinary field for the repair of various tissues, restoring their functions by using scaffolds, cells, and/or bioactive factors. A temporary scaffold acts as an extracellular matrix analog to culture cells and guide the development of new tissue. In this chapter, we discuss the preparation of naturally derived scaffolds of polysaccharide origin, the osteogenic differentiation of mesenchymal stem cells cultured on biomimetic calcium phosphate coatings, and the delivery of biomolecules associated with extracellular matrix mineralization

The ERK and JNK pathways in the regulation of metabolic reprogramming.

Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.Brunel Research Initiative & Enterprise Fund, Brunel University of London (to CB), Kay Kendall Leukemia Fund (KKL443) (to CB), 250 Great Minds Fellowship, University of Leeds (to SP), AMMF Cholangiocarcinoma Charity (to SP and PMC), and Bloodwise (17014) (to SP and CB)

Inhibition of Mitochondrial Complex III Blocks Neuronal Differentiation and Maintains Embryonic Stem Cell Pluripotency

The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor, embryonic stem cells failed to differentiate into dopaminergic neurons, maintaining high Oct4 levels even when subjected to a specific differentiation protocol. Mitochondrial inhibition affected distinct populations of cells present in culture, inducing cell loss in differentiated cells, but not inducing apoptosis in mouse embryonic stem cells. A reduction in overall proliferation rate was observed, corresponding to a slight arrest in S phase. Moreover, antimycin A treatment induced a consistent increase in HIF-1α protein levels. The present work demonstrates that mitochondrial metabolism is critical for neuronal differentiation and emphasizes that modulation of mitochondrial functions through pharmacological approaches can be useful in the context of controlling stem cell maintenance/ differentiation.Fundação para a Ciência e a Tecnologia (FCT) Portugal for grant support (PTDC/EBB-EBI/101114/2008, PTDC/EBB-EBI/ 120634/2010 and PDTC/QUI-BIQ/120652/2010 co-funded by Compete/FEDER/National Funds; and a PhD scholarship attributed to SP (SFRH/BD/ 37933/2007). Center for Neuroscience and Cell Biology (CNC) funding is also supported by FCT (PEst-C/SAU/LA0001/2011). EA’s work was supported by the Swedish Foundation for Strategic Research (SRL Program), Swedish Research Council (DBRM), Karolinska Institutet (SFO Thematic Center in Stem Cells and Regenerative Medicine), and Hjärnfonden

Effects of chlorinated benzenes on diatom fatty acid composition and quantitative morphology. I. 1,2,4-Trichlorobenzene

Cells of the diatom Cyclotella meneghiniana were exposed in a closed system to 0.245 ppm 1,2,4-trichlorobenzene. Response to this chlorinated benzene was monitored over a period of 5 days by quantitative ultrastructure and fatty acid percent composition. Over the time period examined, 41 significant morphological changes and 12 significant changes in fatty acid composition were observed. Autophagic-like vacuoles were frequently observed, indicating lysis of cellular constituents. In general, there was an increase in the C20:5 fatty acid, which may be indicative of photosynthetic impairment, since this fatty acid probably substitutes for linolenic acid in diatoms. The most significant numbers of changes were observed after 8 hr of exposure to this lipophilic toxicant, and these changes occurred in membranous organelles. It is suggested that the daily photoperiodic variation in lipid content of phytoplankton may be an important consideration in evaluating effects of lipohilic toxicants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48069/1/244_2005_Article_BF01225001.pd

Effect of diatom lipid composition on the toxicity of trichlorobenzene. II. Long-term effects of 1,2,3-trichlorobenzene

Exposures of four diatoms, Cyclotella meneghiniana, Melosira italica, Melosira varians , and Synedra filiformis to 0.3 ppm 1,2,3-trichlorobenzene were initiated at the 8th and 11th hours of the light period on a 16:8 h L/D cycle at 20°C. Cell counts, lipid content, and lipid class composition were monitored for 10 days. Melosira italica demonstrated the most long-term effects. Cell counts and chlorophyll a were greatly reduced on the 10th day when exposure was initiated in the 11 th hour of the light period in S. filiformis and in the 8th hour of the light period in M. varians . The data demonstrate that more immediate effects occur when exposures are initiated during periods of high polar lipid content or when polar lipids are being synthesized. Long-term effects are observed when exposure initiation occurs during periods of high neutral lipid content and higher total extractable lipid. The results suggest that the response of diatoms to low levels of chlorinated benzenes is related to normal variation in diel lipid composition. These results are repeatable, they vary with species, and exposures initiated at different times of the day may produce quite different results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48080/1/244_2005_Article_BF01141354.pd