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Sample records for cell niche current

  1. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  2. Engineering the niche for stem cells.

    Science.gov (United States)

    Tan, Shawna; Barker, Nicholas

    2013-12-01

    Much has been made about the potential for stem cells in regenerative medicine but the reality is that the development of actual therapies has been slow. Adult stem cells rely heavily on the assortment of biochemical and biophysical elements that constitute the local microenvironment in which they exist. One goal of biomedicine is to create an artificial yet biofunctional niche to support multipotency, differentiation and proliferation. Such tools would facilitate more conclusive experimentation by biologists, pharmaceutical scientists and tissue engineers. While many bioengineering techniques and platforms are already in use, technological innovations now allow this to be done at a higher resolution and specificity. Ultimately, the multidisciplinary integration of engineering and biology will allow the niche to be generated at a scale that can be clinically exploited. Using the systems that constitute the intestinal, hematopoietic and epidermal tissues, this article summarizes the various approaches and tools currently employed to recreate stem cell niches and also explores recent advances in the field.

  3. The regulatory niche of intestinal stem cells.

    Science.gov (United States)

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders.

  4. The Cell as the First Niche Construction.

    Science.gov (United States)

    Torday, John S

    2016-04-28

    Niche construction nominally describes how organisms can form their own environments, increasing their capacity to adapt to their surroundings. It is hypothesized that the formation of the first cell as 'internal' Niche Construction was the foundation for life, and that subsequent niche constructions were iterative exaptations of that event. The first instantation of niche construction has been faithfully adhered to by returning to the unicellular state, suggesting that the life cycle is zygote to zygote, not adult to adult as is commonly held. The consequent interactions between niche construction and epigenetic inheritance provide a highly robust, interactive, mechanistic way of thinking about evolution being determined by initial conditions rather than merely by chance mutation and selection. This novel perspective offers an opportunity to reappraise the processes involved in evolution mechanistically, allowing for scientifically testable hypotheses rather than relying on metaphors, dogma, teleology and tautology.

  5. The Cell as the First Niche Construction

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2016-04-01

    Full Text Available Niche construction nominally describes how organisms can form their own environments, increasing their capacity to adapt to their surroundings. It is hypothesized that the formation of the first cell as ‘internal’ Niche Construction was the foundation for life, and that subsequent niche constructions were iterative exaptations of that event. The first instantation of niche construction has been faithfully adhered to by returning to the unicellular state, suggesting that the life cycle is zygote to zygote, not adult to adult as is commonly held. The consequent interactions between niche construction and epigenetic inheritance provide a highly robust, interactive, mechanistic way of thinking about evolution being determined by initial conditions rather than merely by chance mutation and selection. This novel perspective offers an opportunity to reappraise the processes involved in evolution mechanistically, allowing for scientifically testable hypotheses rather than relying on metaphors, dogma, teleology and tautology.

  6. Arteriolar niches maintain haematopoietic stem cell quiescence.

    Science.gov (United States)

    Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Mar, Jessica C; Bergman, Aviv; Frenette, Paul S

    2013-10-31

    Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.

  7. Arteriolar niches maintain haematopoietic stem cell quiescence

    Science.gov (United States)

    Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Mar, Jessica C.; Bergman, Aviv; Frenette, Paul S.

    2013-01-01

    Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare NG2+ pericytes, distinct from sinusoid-associated LepR+ cells. Pharmacological or genetic activation of HSC cell cycle alters the distribution of HSCs from NG2+ peri-arteriolar niches to LepR+ peri-sinusoidal niches. Conditional depletion of NG2+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in BM. These results thus indicate that arteriolar niches are indispensable to maintain HSC quiescence. PMID:24107994

  8. The spermatogonial stem cell niche

    NARCIS (Netherlands)

    D.G. de Rooij

    2009-01-01

    Spermatogonial stem cells (SSCs; A(s) spermatogonia) and their direct descendants (A(pr) and A(al) spermatogonia) are preferentially located in those areas of the seminiferous tubules that border on the interstitial tissue. Fewer of these cells are present in tubule areas directly bordering on anoth

  9. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  10. Niche-modulated and niche-modulating genes in bone marrow cells

    Science.gov (United States)

    Cohen, Y; Garach-Jehoshua, O; Bar-Chaim, A; Kornberg, A

    2012-01-01

    Bone marrow (BM) cells depend on their niche for growth and survival. However, the genes modulated by niche stimuli have not been discriminated yet. For this purpose, we investigated BM aspirations from patients with various hematological malignancies. Each aspirate was fractionated, and the various samples were fixed at different time points and analyzed by microarray. Identification of niche-modulated genes relied on sustained change in expression following loss of niche regulation. Compared with the reference (‘authentic') samples, which were fixed immediately following aspiration, the BM samples fixed after longer stay out-of-niche acquired numerous changes in gene-expression profile (GEP). The overall genes modulated included a common subset of functionally diverse genes displaying prompt and sustained ‘switch' in expression irrespective of the tumor type. Interestingly, the ‘switch' in GEP was reversible and turned ‘off-and-on' again in culture conditions, resuming cell–cell–matrix contact versus respread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of tumor cells out-of-niche, and the regression of the ‘contactless switch' was followed by induction of a new set of genes, this time mainly encoding extracellular proteins including angiogenic factors and extracellular matrix proteins. Our data set, being unique in authentic expression design, uncovered niche-modulated and niche-modulating genes capable of controlling homing, expansion and angiogenesis. PMID:23241658

  11. Human embryonic stem cells create their own niche

    Institute of Scientific and Technical Information of China (English)

    Ying Jin

    2007-01-01

    @@ Experimental evidence demonstrates that the ability of stem cells to self-renew and to differentiate into different types of mature cells depends on both their intrinsic genetic programs and external control from their microenvironment or niche. The concept of stem cell niche was first proposed by Schofield in 1978 to describe a microenvironment that supports stem cells in a mammalian hematopoietic system [ 1 ].

  12. Bone Niches, Hematopoietic Stem Cells, and Vessel Formation

    Directory of Open Access Journals (Sweden)

    Roberto Tamma

    2017-01-01

    Full Text Available Bone marrow (BM is a source of hematopoietic stem cells (HSCs. HSCs are localized in both the endosteum, in the so-called endosteal niche, and close to thin-walled and fenestrated sinusoidal vessel in the center of BM, in the so-called vascular niche. HSCs give rise to all types of mature blood cells through a process finely controlled by numerous signals emerging from the bone marrow niches where HSCs reside. This review will focus on the description of the role of BM niches in the control of the fate of HSCs and will also highlight the role of the BM niches in the regulation of vasculogenesis and angiogenesis. Moreover, alterations of the signals in niche microenvironment are involved in many aspects of tumor progression and vascularization and further knowledge could provide the basis for the development of new therapeutic strategies.

  13. Modeling dynamics of mutants in heterogeneous stem cell niche

    Science.gov (United States)

    Shahriyari, L.; Mahdipour-Shirayeh, A.

    2017-02-01

    Studying the stem cell (SC) niche architecture is a crucial step for investigating the process of oncogenesis and obtaining an effective stem cell therapy for various cancers. Recently, it has been observed that there are two groups of SCs in the SC niche collaborating with each other to maintain tissue homeostasis: border stem cells (BSCs), which are responsible in controlling the number of non-stem cells as well as stem cells, and central stem cells (CeSCs), which regulate the SC niche. Here, we develop a bi-compartmental stochastic model for the SC niche to study the spread of mutants within the niche. The analytic calculations and numeric simulations, which are in perfect agreement, reveal that in order to delay the spread of mutants in the SC niche, a small but non-zero number of SC proliferations must occur in the CeSC compartment. Moreover, the migration of BSCs to CeSCs delays the spread of mutants. Furthermore, the fixation probability of mutants in the SC niche is independent of types of SC division as long as all SCs do not divide fully asymmetrically. Additionally, the progeny of CeSCs have a much higher chance than the progeny of BSCs to take over the entire niche.

  14. Elements of a neural stem cell niche derived from embryonic stem cells.

    Science.gov (United States)

    Pierret, Chris; Spears, Kathleen; Morrison, Jason A; Maruniak, Joel A; Katz, Martin L; Kirk, Mark D

    2007-12-01

    Recent studies show that adult neural tissues can harbor stem cells within unique niches. In the mammalian central nervous system, neural stem cell (NSC) niches have been identified in the dentate gyrus and the subventricular zone (SVZ). Stem cells in the well-characterized SVZ exist in a microenvironment established by surrounding cells and tissue components, including transit-amplifying cells, neuroblasts, ependymal cells, blood vessels, and a basal lamina. Within this microenvironment, stem cell properties, including proliferation and differentiation, are maintained. Current NSC culture techniques often include the addition of molecular components found within the in vivo niche, such as mitogenic growth factors. Some protocols use bio-scaffolds to mimic the physical growth environment of living tissue. We describe a novel NSC culture system, derived from embryonic stem (ES) cells, that displays elements of an NSC niche in the absence of exogenously applied mitogens or complex physical scaffolding. Mouse ES cells were neuralized with retinoic acid and plated on an entactin-collagen-laminin-coated glass surface at high density (250,000 cells/cm(2)). Six to eight days after plating, complex multicellular structures consisting of heterogeneous cell types developed spontaneously. NSC and progenitor cell proliferation and differentiation continued within these structures. The identity of cellular and molecular components within the cultures was documented using RT-PCR, immunocytochemistry, and neurosphere-forming assays. We show that ES cells can be induced to form structures that exhibit key properties of a developing NSC niche. We believe this system can serve as a useful model for studies of neurogenesis and stem cell maintenance in the NSC niche as well as for applications in stem cell transplantation.

  15. Recapitulation of the embryonic cardiovascular progenitor cell niche.

    Science.gov (United States)

    Schenke-Layland, Katja; Nsair, Ali; Van Handel, Ben; Angelis, Ekaterini; Gluck, Jessica M; Votteler, Miriam; Goldhaber, Joshua I; Mikkola, Hanna K; Kahn, Michael; Maclellan, William R

    2011-04-01

    Stem or progenitor cell populations are often established in unique niche microenvironments that regulate cell fate decisions. Although niches have been shown to be critical for the normal development of several tissues, their role in the cardiovascular system is poorly understood. In this study, we characterized the cardiovascular progenitor cell (CPC) niche in developing human and mouse hearts, identifying signaling pathways and extracellular matrix (ECM) proteins that are crucial for CPC maintenance and expansion. We demonstrate that collagen IV (ColIV) and β-catenin-dependent signaling are essential for maintaining and expanding undifferentiated CPCs. Since niches are three-dimensional (3D) structures, we investigated the impact of a 3D microenvironment that mimics the in vivo niche ECM. Employing electrospinning technologies, 3D in vitro niche substrates were bioengineered to serve as culture inserts. The three-dimensionality of these structures increased mouse embryonic stem cell differentiation into CPCs when compared to 2D control cultures, which was further enhanced by incorporation of ColIV into the substrates. Inhibiting p300-dependent β-catenin signals with the small molecule IQ1 facilitated further expansion of CPCs. Our study represents an innovative approach to bioengineer cardiac niches that can serve as unique 3D in vitro systems to facilitate CPC expansion and study CPC biology.

  16. Artificial hematopoietic stem cell niche: bioscaffolds to microfluidics to mathematical simulations.

    Science.gov (United States)

    Didwania, Maruti; Didwania, Anjani; Mehta, Geeta; Basak, Grzegorz W; Yasukawa, Satoshi; Takayama, Shuichi; de Necochea-Campion, Rosalia; Srivastava, Anand; Carrier, Ewa

    2011-01-01

    Due to the recent advancements in stem cell biology and engineering, scientists have been increasingly interested in creating in vitro niches for embryonic and adult stem cells, and, following induction and differentiation with the appropriate media, the production of large scale blood production. This artificially created niche for hematopoietic cells will be composed of three materials: the stem cells themselves, the scaffold surrounding the stem cell, and the media used to expand and differentiate the stem cells. This paper will examine the recent advancements in technology for each of these relating to the development of an artificial stem cell niche. Many key aspects of the artificial niche need to be improved on before we can scale up the engineered device for large scale blood production including more efficient methods of retrieval of the embroid bodies produced from the microfluidic channels. The current state of experimental methods such as these as well as relevant discoveries in related fields that could be applied to artificial niche technology is described in this paper. Furthermore, we present a mathematical model to describe cell expansion in the artificial hematopoietic stem cell niche in order to design and optimize a scaled-up bioreactor. The mathematical model describes the dynamics of expansion, and maintenance of homeostasis in the bioreactor.

  17. Stem cell autotomy and niche interaction in differentsystems

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The best known cases of cell autotomy are theformation of erythrocytes and thrombocytes (platelets)from progenitor cells that reside in special niches.Recently, autotomy of stem cells and its enigmaticinteraction with the niche has been reported from malegermline stem cells (GSCs) in several insect species.First described in lepidopterans, the silkmoth, followedby the gipsy moth and consecutively in hemipterans,foremost the milkweed bug. In both, moths and themilkweed bug, GSCs form finger-like projectionstoward the niche, the apical cells (homologs of thehub cells in Drosophila). Whereas in the milkweedbug the projection terminals remain at the surfaceof the niche cells, in the gipsy moth they protrudedeeply into the singular niche cell. In both cases, theprojections undergo serial retrograde fragmentationwith progressing signs of autophagy. In the gipsy moth,the autotomized vesicles are phagocytized and digestedby the niche cell. In the milkweed bug the autotomizedvesicles accumulate at the niche surface and disintegrate.Autotomy and sprouting of new projectionsappears to occur continuously. The significance of theGSC-niche interactions, however, remains enigmatic.Our concept on the signaling relationship betweenstem cell-niche in general and GSC and niche (hubcells and cyst stem cells) in particular has been greatlyshaped by Drosophila melanogaster. In comparingthe interactions of GSCs with their niche in Drosophilawith those in species exhibiting GSC autotomy itis obvious that additional or alternative modes ofstem cell-niche communication exist. Thus, essentialsignaling pathways, including niche-stem cell adhesion(E-cadherin) and the direction of asymmetrical GSCdivision - as they were found in Drosophila - can hardlybe translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomyof GSC projections shows remarkable similarities withWallerian axonal destruction, developmental axonpruning and dying

  18. Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties.

    Science.gov (United States)

    Tong, Xinming; Yang, Fan

    2014-02-01

    Hydrogels have been widely used as artificial cell niche to mimic extracellular matrix with tunable properties. However, changing biochemical cues in hydrogels developed-to-date would often induce simultaneous changes in mechanical properties, which do not support mechanistic studies on stem cell-niche interactions. Here we report the development of a PEG-based interpenetrating network (IPN), which is composed of two polymer networks that can independently and simultaneously crosslink to form hydrogels in a cell-friendly manner. The resulting IPN hydrogel allows independently tunable biochemical and mechanical properties, as well as stable and more homogeneous presentation of biochemical ligands in 3D than currently available methods. We demonstrate the potential of our IPN platform for elucidating stem cell-niche interactions by modulating osteogenic differentiation of human adipose-derived stem cells. The versatility of such IPN hydrogels is further demonstrated using three distinct and widely used polymers to form the mechanical network while keeping the biochemical network constant.

  19. Evolving concepts on the microenvironmental niche for hematopoietic stem cells.

    NARCIS (Netherlands)

    Raaijmakers, M.G.P.; Scadden, D.T.

    2008-01-01

    PURPOSE OF REVIEW: The hematopoietic stem cell niche is critical for the maintenance and proliferation of hematopoietic stem cells and, as such, is not only essential for steady-state hematopoiesis but may also be relevant to hematologic disease. The present review discusses recent advances in the u

  20. Stemness & Niche sans Frontiers – The Cancer Stem Cell myth

    Directory of Open Access Journals (Sweden)

    Editorial

    2014-04-01

    Full Text Available The niche or the environment in which the cells reside and/or develop plays a major role in influencing the behaviour and characteristics of those cells. In case of normal stem cells, the niche acts as a physical anchoring site and the adhesion molecules therein help with their interaction [1]. The niche secretes extrinsic factors that control the self-renewal and lineage differentiation of the stem cells, thereby guiding them towards a pre-determined path of differentiation. For eg. stem cells in the corneal limbus give rise to corneal epithelial cells, stem cells in liver give rise to hepatocytes etc. which happen within the same organ or tissue. The bone marrow stem cells however have been found to come out of the marrow into the circulation, reach sites far away from their origin and have been reported to home to the site of injury and help in tissue repair either by direct differentiation to the cells native to the site of injury or by paracrine effect or other mechanisms [2]. In both these examples, the stem cells of relevance tend to differentiate into a mature cell of the surrounding niche/organ. However when it comes to cancer stem cells, the niche needs to be perceived in a different light. The cancer stem cells possess the ability to mobilize to distant sites and instead of differentiating to the cell type native to the distant metastasized site, these cancer stem cells either stay in a latent state or establish the tumour there, which makes us hypothesize that they might possess the capacity to modify the environment or the niche at that distant metastasized site. For instance, tumour cells in breast cancer have been found to disseminate to the bone marrow at a very early stage of cancer and these disseminated tumor cells (DTC have been found to possess a cancer stem cell phenotype [3]. These DTCs have been reported to persist for long and have been suggested to play a role in cancer recurrence [4]. Also these DTCs acquire a highly

  1. The spinal cord ependymal region: a stem cell niche in the caudal central nervous system.

    Science.gov (United States)

    Hugnot, Jean Philippe; Franzen, Rachelle

    2011-01-01

    In the brain, specific signalling pathways localized in highly organized regions called niches, allow the persistence of a pool of stem and progenitor cells that generate new neurons and glial cells in adulthood. Much less is known on the spinal cord central canal niche where a sustained adult neurogenesis is not observed. Here we review our current knowledge of this caudal niche in normal and pathological situations. Far from being a simple layer of homogenous cells, this region is composed of several cell types localized at specific locations, expressing characteristic markers and with different morphologies and functions. We further report on a screen of online gene-expression databases to better define this spinal cord niche. Several genes were found to be preferentially expressed within or around the central canal region (Bmp6, CXCR4, Gdf10, Fzd3, Mdk, Nrtn, Rbp1, Shh, Sox4, Wnt7a) some of which by specific cellular subtypes. In depth characterization of the spinal cord niche constitutes a framework to make the most out of this endogenous cell pool in spinal cord disorders.

  2. Stem cell niche failure concerns bone marrow failure--a diagnostic and therapeutic consideration.

    Science.gov (United States)

    Law, Sujata; Chaudhuri, Samaresh

    2011-01-01

    Diseases of the bone marrow often referred to as "Bone marrow failure" have complicated pathophysiological picture with respect to hematopoietic systemic function. The reason for such bone marrow disorder is not well understood till date, although some sporadic etiological sources have been described earlier. With the advent of current investigations, hematopoietic stem cell involvement together with the failure of signaling interaction within the bone marrow niche has been found to reveal interesting correlations with the disease onset. The present review furnishes justification for bone marrow failure as a concern of stem cell niche failure and hints at providing important clues for disease diagnosis and therapeutic maneuver.

  3. A family business: stem cell progeny join the niche to regulate homeostasis.

    Science.gov (United States)

    Hsu, Ya-Chieh; Fuchs, Elaine

    2012-01-23

    Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

  4. Stem-cell niches: nursery rhymes across kingdoms.

    Science.gov (United States)

    Scheres, Ben

    2007-05-01

    Despite the large evolutionary distance between the plant and animal kingdoms, stem cells in both reside in specialized cellular contexts called stem-cell niches. Although stem-cell-specification factors have been recruited from plant-specific gene families, maintenance factors that repress stem-cell differentiation are conserved between plants and animals. Recent evidence indicates that stem cells in multicellular organisms can be specified by kingdom-specific patterning mechanisms that connect to a related core of epigenetic stem-cell factors.

  5. Niche interactions in epidermal stem cells

    Institute of Scientific and Technical Information of China (English)

    Hye-Ryung Choi; Sang-Young Byun; Soon-Hyo Kwon; Kyoung-Chan Park

    2015-01-01

    Within the epidermis and dermis of the skin, cellssecrete and are surrounded by the extracellular matrix(ECM), which provides structural and biochemicalsupport. The ECM of the epidermis is the basementmembrane, and collagen and other dermal componentsconstitute the ECM of the dermis. There is significantvariation in the composition of the ECM of the epidermisand dermis, which can affect "cell to cell" and "cellto ECM" interactions. These interactions, in turn, caninfluence biological responses, aging, and woundhealing; abnormal ECM signaling likely contributes toskin diseases. Thus, strategies for manipulating cell-ECM interactions are critical for treating wounds and avariety of skin diseases. Many of these strategies focuson epidermal stem cells, which reside in a unique nichein which the ECM is the most important component;interactions between the ECM and epidermal stemcells play a major role in regulating stem cell fate. Asthey constitute a major portion of the ECM, it is likelythat integrins and type Ⅳ collagens are important instem cell regulation and maintenance. In this review,we highlight recent research-including our previouswork-exploring the role that the ECM and its associatedcomponents play in shaping the epidermal stem cellniche.

  6. Meninges: from protective membrane to stem cell niche.

    Science.gov (United States)

    Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

    2012-01-01

    Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction.

  7. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

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    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs.

  8. Implications of irradiating the subventricular zone stem cell niche

    Directory of Open Access Journals (Sweden)

    Vivian Capilla-Gonzalez

    2016-03-01

    Full Text Available Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.

  9. Implications of irradiating the subventricular zone stem cell niche.

    Science.gov (United States)

    Capilla-Gonzalez, Vivian; Bonsu, Janice M; Redmond, Kristin J; Garcia-Verdugo, Jose Manuel; Quiñones-Hinojosa, Alfredo

    2016-03-01

    Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs) reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.

  10. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells

    Science.gov (United States)

    Ottone, Cristina; Krusche, Benjamin; Whitby, Ariadne; Clements, Melanie; Quadrato, Giorgia; Pitulescu, Mara E.; Adams, Ralf H.; Parrinello, Simona

    2014-01-01

    The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculature-secreted soluble factors promote lineage progression of committed progenitors. Here we specifically investigated the role of cell-cell contact-dependent signalling in the vascular niche. Unexpectedly, we find that direct cell-cell interactions with endothelial cells enforces quiescence and promotes stem cell identity. Mechanistically, endothelial ephrinB2 and Jagged1 mediate these effects by suppressing cell-cycle entry downstream of mitogens and inducing stemness genes to jointly inhibit differentiation. In vivo, endothelial-specific ablation of either of the genes which encode these proteins, Efnb2 and Jag1 respectively, aberrantly activates quiescent stem cells, resulting in depletion. Thus, we identify the vasculature as a critical niche compartment for stem cell maintenance, furthering our understanding of how anchorage to the niche maintains stem cells within a pro-differentiative microenvironment. PMID:25283993

  11. Mesenchymal stem cells: a perspective from in vitro cultures to in vivo migration and niches

    Directory of Open Access Journals (Sweden)

    A Augello

    2010-09-01

    Full Text Available Mesenchymal Stromal Progenitor/Stem Cells (MSCs are a rare population of non-hematopoietic stromal cells, present in the bone marrow and most connective tissues of the body. They are capable of differentiation into mesenchymal tissues such as bone, cartilage, adipose tissue and muscle. In the absence of specific markers, MSCs have been defined following isolation and culture expansion, by their expression of various molecules including CD90, CD105 and CD73 and absence of markers like CD34, CD45, and CD14. MSCs have extensive proliferative ability in culture in an uncommitted state while retaining their multilineage differentiation potential, which make them attractive candidates for biological cell-based tissue repair approaches. However, their identity in their tissues of origin is not clear and the niches in which they reside are not defined. This review addresses the current state of MSC research including the differentiation potency of culture expanded MSCs, expression of chemokines and their receptors in MSCs – both relevant issues for the advocated use of MSCs for tissue repair and their systemic delivery to the affected tissues. It also reviews current knowledge of MSC niches in their native tissues, addressing the relationship with pericytes. Finally, it provides a scientific basis for the requirement of a thorough characterisation of the endogenous MSC niches within their native tissues in vivo. The knowledge of MSC niches will instruct development of innovative therapeutic measures such as producing pharmacological substances that target endogenous MSCs and their niches in order to activate and guide intrinsic repair and to improve disease outcomes.

  12. Stem Cell Niches in Glioblastoma: A Neuropathological View

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    Davide Schiffer

    2014-01-01

    Full Text Available Glioblastoma (GBM stem cells (GSCs, responsible for tumor growth, recurrence, and resistance to therapies, are considered the real therapeutic target, if they had no molecular mechanisms of resistance, in comparison with the mass of more differentiated cells which are insensitive to therapies just because of being differentiated and nonproliferating. GSCs occur in tumor niches where both stemness status and angiogenesis are conditioned by the microenvironment. In both perivascular and perinecrotic niches, hypoxia plays a fundamental role. Fifteen glioblastomas have been studied by immunohistochemistry and immunofluorescence for stemness and differentiation antigens. It has been found that circumscribed necroses develop inside hyperproliferating areas that are characterized by high expression of stemness antigens. Necrosis developed inside them because of the imbalance between the proliferation of tumor cells and endothelial cells; it reduces the number of GSCs to a thin ring around the former hyperproliferating area. The perinecrotic GSCs are nothing else that the survivors remnants of those populating hyperproliferating areas. In the tumor, GSCs coincide with malignant areas so that the need to detect where they are located is not so urgent.

  13. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  14. Oxidized alginate hydrogels as niche environments for corneal epithelial cells.

    Science.gov (United States)

    Wright, Bernice; De Bank, Paul A; Luetchford, Kim A; Acosta, Fernando R; Connon, Che J

    2014-10-01

    Chemical and biochemical modification of hydrogels is one strategy to create physiological constructs that maintain cell function. The aim of this study was to apply oxidised alginate hydrogels as a basis for development of a biomimetic niche for limbal epithelial stem cells that may be applied to treating corneal dysfunction. The stem phenotype of bovine limbal epithelial cells (LEC) and the viability of corneal epithelial cells (CEC) were examined in oxidised alginate gels containing collagen IV over a 3-day culture period. Oxidation increased cell viability (P ≤ 0.05) and this improved further with addition of collagen IV (P ≤ 0.01). Oxidised gels presented larger internal pores (diameter: 0.2-0.8 µm) than unmodified gels (pore diameter: 0.05-0.1 µm) and were significantly less stiff (P ≤ 0.001), indicating that an increase in pore size and a decrease in stiffness contributed to improved cell viability. The diffusion of collagen IV from oxidised alginate gels was similar to that of unmodified gels suggesting that oxidation may not affect the retention of extracellular matrix proteins in alginate gels. These data demonstrate that oxidised alginate gels containing corneal extracellular matrix proteins can influence corneal epithelial cell function in a manner that may impact beneficially on corneal wound healing therapy.

  15. Hematopoietic stem cells are coordinated by the molecular cues of the endosteal niche.

    NARCIS (Netherlands)

    Huurne, M.C. ter; Figdor, C.G.; Torensma, R.

    2010-01-01

    Hematopoietic stem cells (HSCs) accomplish a complex task. On a daily base billions of the 8 different mature cells are delivered in the right proportions. HSCs are located in niches located at several locations in the body. Communication between these spatially separated niches is accomplished by s

  16. Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance.

    Science.gov (United States)

    Lee, Gina; Hall, Robert R; Ahmed, Atique U

    2016-10-01

    Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and disease progression. This theory hypothesizes that a population of the tumor cell with similar functional and phenotypic characteristics as normal tissue stem cells are responsible for formation and advancement of many human cancers. The CSCs subpopulation can differentiate into non-CSC tumor cells and promote phenotypic and functional heterogeneity within the tumor. The presence of CSCs has been reported in a number of human cancers including blood, breast, brain, colon, lung, pancreas prostate and liver. Although the origin of CSCs remains a mystery, recent reports suggest that the phenotypic characteristics of CSCs may be plastic and are influenced by the microenvironment specific for the individual tumor. Such factors unique to each tumor preserve the dynamic balance between CSCs to non-CSCs cell fate, as well as maintain the proper equilibrium. Alternating such equilibrium via dedifferentiation can result in aggressiveness, as CSCs are considered to be more resistant to the conventional cancer treatments of chemotherapy and radiation. Understanding how the tumoral microenvironment affects the plasticity driven CSC niche will be critical for developing a more effective treatment for cancer by eliminating its aggressive and recurring nature that now is believed to be perpetuated by CSCs.

  17. Traffic jam functions in a branched pathway from Notch activation to niche cell fate.

    Science.gov (United States)

    Wingert, Lindsey; DiNardo, Stephen

    2015-07-01

    The niche directs key behaviors of its resident stem cells, and is thus crucial for tissue maintenance, repair and longevity. However, little is known about the genetic pathways that guide niche specification and development. The male germline stem cell niche in Drosophila houses two stem cell populations and is specified within the embryonic gonad, thus making it an excellent model for studying niche development. The hub cells that form the niche are specified early by Notch activation. Over the next few hours, these individual cells then cluster together and take up a defined position before expressing markers of hub cell differentiation. This timing suggests that there are other factors for niche development yet to be defined. Here, we have identified a role for the large Maf transcription factor Traffic jam (Tj) in hub cell specification downstream of Notch. Tj downregulation is the first detectable effect of Notch activation in hub cells. Furthermore, Tj depletion is sufficient to generate ectopic hub cells that can recruit stem cells. Surprisingly, ectopic niche cells in tj mutants remain dispersed in the absence of Notch activation. This led us to uncover a branched pathway downstream of Notch in which Bowl functions to direct hub cell assembly in parallel to Tj downregulation.

  18. Not all renal stem cell niches are the same: anatomy of an evolution

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    Clara Gerosa

    2016-08-01

    Full Text Available The renal stem cell niche represents the most important structure of the developing kidney, responsible for nephrogenesis. Recently, some Authors have reported, at ultrastructural level, a previously unknown complexity of the architecture of renal stem cell niche in experimental models. This study was aimed at studying, at histological level, the anatomy of renal stem cell niches in the human fetal kidney. To this end, ten fetal kidneys, whose gestational ages ranged from 11 up to 24 weeks, were studied. H&E-stained sections were observed at high power. The study of the anatomy of renal stem cell niches in the human kidney revealed a previously unreported complexity: some niches appeared as a roundish arrangement of mesenchymal cells; others showed the initial phases of induction by ureteric buds; in other niches the process of mesenchymal epithelial transition was more evident; finally, in other stem cell niches the first signs of nephron origin were detectable. These findings suggest the existence of niches with different anatomy in the same kidney, indicating different stages of evolution even in adjacent niches. All stem cell niches were in strict contact with the capsular cells, suggesting a major role of the renal capsule in nephrogenesis. Finally, our study confirms the existence of a strict contact between the bud tip cells and the surrounding mesenchyme in the human developing kidney, giving a morphological support to the theory of intercellular channels allowing the passage of transcription factors from the epithelial to the mesenchymal stem/progenitors cells.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  19. NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared niche

    OpenAIRE

    Chang, Chiung-Ying; Pasolli, H. Amalia; Giannopoulou, Eugenia G.; Guasch, Géraldine; Gronostajski, Richard M.; Elemento, Olivier; Fuchs, Elaine

    2013-01-01

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation1–4. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment2,5. Dissecting the inter-stem-ce...

  20. Optimization of Femtosecond Laser Polymerized Structural Niches to Control Mesenchymal Stromal Cell Fate in Culture

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    Manuela T. Raimondi

    2014-06-01

    Full Text Available We applied two-photon polymerization to fabricate 3D synthetic niches arranged in complex patterns to study the effect of mechano-topological parameters on morphology, renewal and differentiation of rat mesenchymal stromal cells. Niches were formed in a photoresist with low auto-fluorescence, which enabled the clear visualization of the fluorescence emission of the markers used for biological diagnostics within the internal niche structure. The niches were structurally stable in culture up to three weeks. At three weeks of expansion in the niches, cell density increased by almost 10-fold and was 67% greater than in monolayer culture. Evidence of lineage commitment was observed in monolayer culture surrounding the structural niches, and within cell aggregates, but not inside the niches. Thus, structural niches were able not only to direct stem cell homing and colony formation, but also to guide aggregate formation, providing increased surface-to-volume ratios and space for stem cells to adhere and renew, respectively.

  1. Inhibition of the integrin signal constitutes a mouse iPS cell niche.

    Science.gov (United States)

    Higuchi, Sayaka; Yoshina, Sawako; Mitani, Shohei

    2016-09-01

    Stem cells are regulated by their surrounding microenvironments, called niche, such as cell-cell interaction and extracellular matrix. Classically, feeder cells as a niche have been used in the culture of iPS cells from both the mouse and the human. However, the regulation mechanism of stem cells by feeder cells as a niche still have been partially unclear. In this study, we used three murine iPS cell lines, iPS-MEF-Ng-20D-17, iPS-MEF-Ng-178B-5 and iPS-MEF-Fb/Ng-440A-3, which were generated by different reprogramming methods. In general, these cell lines commonly need the feeder cells as a niche to culture. Recently, the effect of substrate stiffness is known in stem cell study. First, we focused on the mechanical properties of feeder cells, and then we speculated that feeder-less culture might be made possible by using molecules in place of the mechanical properties of the niche. Finally, we found that the combination of disintegrin (echistatin) and 2i (GSK3 inhibitor and MEK inhibitor) is a sufficient condition for three murine iPS culture. This novel method of mimicking the murine iPS cell niche may be useful to understand signaling pathways to maintain the pluripotency of stem cells.

  2. Extreme divergence of Wolbachia tropism for the stem-cell-niche in the Drosophila testis.

    Science.gov (United States)

    Toomey, Michelle E; Frydman, Horacio M

    2014-12-01

    Microbial tropism, the infection of specific cells and tissues by a microorganism, is a fundamental aspect of host-microbe interactions. The intracellular bacteria Wolbachia have a peculiar tropism for the stem cell niches in the Drosophila ovary, the microenvironments that support the cells producing the eggs. The molecular underpinnings of Wolbachia stem cell niche tropism are unknown. We have previously shown that the patterns of tropism in the ovary show a high degree of conservation across the Wolbachia lineage, with closely related Wolbachia strains usually displaying the same pattern of stem cell niche tropism. It has also been shown that tropism to these structures in the ovary facilitates both vertical and horizontal transmission, providing a strong selective pressure towards evolutionary conservation of tropism. Here we show great disparity in the evolutionary conservation and underlying mechanisms of stem cell niche tropism between male and female gonads. In contrast to females, niche tropism in the male testis is not pervasive, present in only 45% of niches analyzed. The patterns of niche tropism in the testis are not evolutionarily maintained across the Wolbachia lineage, unlike what was shown in the females. Furthermore, hub tropism does not correlate with cytoplasmic incompatibility, a Wolbachia-driven phenotype imprinted during spermatogenesis. Towards identifying the molecular mechanism of hub tropism, we performed hybrid analyses of Wolbachia strains in non-native hosts. These results indicate that both Wolbachia and host derived factors play a role in the targeting of the stem cell niche in the testis. Surprisingly, even closely related Wolbachia strains in Drosophila melanogaster, derived from a single ancestor only 8,000 years ago, have significantly different tropisms to the hub, highlighting that stem cell niche tropism is rapidly diverging in males. These findings provide a powerful system to investigate the mechanisms and evolution of

  3. Escargot Restricts Niche Cell to Stem Cell Conversion in the Drosophila Testis

    Directory of Open Access Journals (Sweden)

    Justin Voog

    2014-05-01

    Full Text Available Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behavior. Somatic hub cells in the Drosophila testis regulate the behavior of cyst stem cells (CySCs and germline stem cells (GSCs and are a primary component of the testis stem cell niche. The shutoff (shof mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg. Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the corepressor C-terminal binding protein (CtBP, which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo.

  4. Spatial distribution of niche and stem cells in ex vivo human limbal cultures.

    Science.gov (United States)

    Mariappan, Indumathi; Kacham, Santhosh; Purushotham, Jyothi; Maddileti, Savitri; Siamwala, Jamila; Sangwan, Virender Singh

    2014-11-01

    Stem cells at the limbus mediate corneal epithelial regeneration and regulate normal tissue homeostasis. Ex vivo cultured limbal epithelial transplantations are being widely practiced in the treatment of limbal stem cell deficiency. In this report, we examined whether the limbal niche cells that nurture and regulate epithelial stem cells coexist in ex vivo limbal cultures. We also compared the inherent differences between explant and suspension culture systems in terms of spatial distribution of niche cells and their effect on epithelial stem cell proliferation, migration, and differentiation in vitro. We report that the stem cell content of both culture systems was similar, explaining the comparable clinical outcomes reported using these two methods. We also showed that the niche cells get expanded in culture and the nestin-positive cells migrate at the leading edges to direct epithelial cell migration in suspension cultures, whereas they are limited to the intact niche in explant cultures. We provide evidence that C/EBPδ-positive, p15-positive, and quiescent, label-retaining, early activated stem cells migrate at the leading edges to regulate epithelial cell proliferation in explant cultures, and this position effect is lost in early suspension cultures. However, in confluent suspension cultures, the stem cells and niche cells interact with each another, migrate in spiraling patterns, and self-organize to form three-dimensional niche-like compartments resembling the limbal crypts and thereby reestablish the position effect. These 3D-sphere clusters are enriched with nestin-, vimentin-, S100-, and p27-positive niche cells and p15-, p21-, p63α-, C/EBPδ-, ABCG2-, and Pax6-positive quiescent epithelial stem cells.

  5. Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila

    Science.gov (United States)

    Bailey, Andrew P.; Koster, Grielof; Guillermier, Christelle; Hirst, Elizabeth M.A.; MacRae, James I.; Lechene, Claude P.; Postle, Anthony D.; Gould, Alex P.

    2015-01-01

    Summary Stem cells reside in specialized microenvironments known as niches. During Drosophila development, glial cells provide a niche that sustains the proliferation of neural stem cells (neuroblasts) during starvation. We now find that the glial cell niche also preserves neuroblast proliferation under conditions of hypoxia and oxidative stress. Lipid droplets that form in niche glia during oxidative stress limit the levels of reactive oxygen species (ROS) and inhibit the oxidation of polyunsaturated fatty acids (PUFAs). These droplets protect glia and also neuroblasts from peroxidation chain reactions that can damage many types of macromolecules. The underlying antioxidant mechanism involves diverting PUFAs, including diet-derived linoleic acid, away from membranes to the core of lipid droplets, where they are less vulnerable to peroxidation. This study reveals an antioxidant role for lipid droplets that could be relevant in many different biological contexts. PMID:26451484

  6. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  7. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Cécile eCoste

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  8. The tale of early hematopoietic cell seeding in the bone marrow niche.

    Science.gov (United States)

    Yaniv, Isaac; Stein, Jerry; Farkas, Daniel L; Askenasy, Nadir

    2006-02-01

    Since introduction of the notion of a "niche" that hosts engraftment and activity of hematopoietic cells, there is a massive effort to discover its structure and decipher its function. Our understanding of the niche is continuously changing with reinterpretation of traditional concepts and apprehension of new insights into the biology of hematopoietic cell homing, seeding, and engraftment. Here we discuss some of the early events in hematopoietic stem cell seeding and engraftment and propose a perspective based on visualization of labeled bone marrow cells in real time in vivo. Primary seeding of hematopoietic cells in the bone marrow niches evolves as a complex and dynamic process; however, it follows discrete topological and chronological patterns. Initial seeding occurs on the endosteal surface of the marrow, which includes heterogeneous niches for primary seeding. Several days after transplantation the endosteal niches become more restrictive, hosting primarily mitotically quiescent cells, and gradual centripetal migration is accompanied by engagement in proliferation and differentiation. The hematopoietic niches evolve as heterogeneous three-dimensional microenvironments that are continuously changing over time.

  9. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

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    Roy Blum

    Full Text Available BACKGROUND: Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system. METHODOLOGY/PRINCIPAL FINDINGS: We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2, lipid metabolism (e.g., Srebp1 and cell migration (e.g., Areb6 and Rreb1. Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche. CONCLUSIONS/SIGNIFICANCE: We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may

  10. A single cell functions as a tissue-specific stem cell and the in vitro niche-forming cell.

    Science.gov (United States)

    Ghosh, Moumita; Helm, Karen M; Smith, Russell W; Giordanengo, Matthew S; Li, Bilan; Shen, Hongmei; Reynolds, Susan D

    2011-09-01

    Tissue-specific stem cell (TSC) behavior is determined by the stem cell niche. However, delineation of the TSC-niche interaction requires purification of both entities. We reasoned that the niche could be defined by the location of the TSC. We demonstrate that a single CD49f(bright)/Sca1(+)/ALDH(+) basal cell generates rare label-retaining cells and abundant label-diluting cells. Label-retaining and label-diluting cells were located in the rimmed domain of a unique clone type, the rimmed clone. The TSC property of self-renewal was tested by serial passage at clonal density and analysis of clone-forming cell frequency. A single clone could be passaged up to five times and formed only rimmed clones. Thus, rimmed clone formation was a cell-intrinsic property. Differentiation potential was evaluated in air-liquid interface cultures. Homogenous cultures of rimmed clones were highly mitotic but were refractory to standard differentiation signals. However, rimmed clones that were cocultured with unfractionated tracheal cells generated each of the cell types found in the tracheal epithelium. Thus, the default niche is promitotic: Multipotential differentiation requires adaptation of the niche. Because lung TSCs are typically evaluated after injury, the behavior of CD49f(bright)/Sca1(+)/ALDH(+) cells was tested in normal and naphthalene-treated mice. These cells were mitotically active in the normal and repaired epithelium, their proliferation rate increased in response to injury, and they retained label for 34 days. We conclude that the CD49f(bright)/Sca1(+)/ALDH(+) tracheal basal cell is a TSC, that it generates its own niche in vitro, and that it participates in tracheal epithelial homeostasis and repair.

  11. Synthetic niches for differentiation of human embryonic stem cells bypassing embryoid body formation.

    Science.gov (United States)

    Liu, Yarong; Fox, Victoria; Lei, Yuning; Hu, Biliang; Joo, Kye-Il; Wang, Pin

    2014-07-01

    The unique self-renewal and pluripotency features of human embryonic stem cells (hESCs) offer the potential for unlimited development of novel cell therapies. Currently, hESCs are cultured and differentiated using methods, such as monolayer culture and embryoid body (EB) formation. As such, achieving efficient differentiation into higher order structures remains a challenge, as well as maintaining cell viability during differentiation into homogeneous cell populations. Here, we describe the application of highly porous polymer scaffolds as synthetic stem cell niches. Bypassing the EB formation step, these scaffolds are capable of three-dimensional culture of undifferentiated hESCs and subsequent directed differentiation into three primary germ layers. H9 hESCs were successfully maintained and proliferated in biodegradable polymer scaffolds based on poly (lactic-co-glycolic acid) (PLGA). The results showed that cells within PLGA scaffolds retained characteristics of undifferentiated pluripotent stem cells. Moreover, the scaffolds allowed differentiation towards the lineage of interest by the addition of growth factors to the culture system. The in vivo transplantation study revealed that the scaffolds could provide a microenvironment that enabled hESCs to interact with their surroundings, thereby promoting cell differentiation. Therefore, this approach, which provides a unique culture/differentiation system for hESCs, will find its utility in various stem cell-based tissue-engineering applications.

  12. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

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    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  13. Sliding Hydrogels with Mobile Molecular Ligands and Crosslinks as 3D Stem Cell Niche.

    Science.gov (United States)

    Tong, Xinming; Yang, Fan

    2016-09-01

    The development of a sliding hydrogel with mobile crosslinks and biochemical ligands as a 3D stem cell niche is reported. The molecular mobility of this sliding hydrogel allows stem cells to reorganize the surrounding ligands and change their morphology in 3D. Without changing matrix stiffness, sliding hydrogels support efficient stem cell differentiation toward multiple lineages including adipogenesis, chondrogenesis, and osteogenesis.

  14. CD133(+) niches and single cells in glioblastoma have different phenotypes

    DEFF Research Database (Denmark)

    Christensen, Karina; Schrøder, Henrik Daa; Kristensen, Bjarne Winther

    2011-01-01

    Putative CD133(+) brain tumor stem cells have been shown to be located in niches and as single cells. This is the first study providing insight into the different phenotypes of CD133(+) cells in glioblastoma according to localization. Paraffin sections were stained by double immunofluorescence...

  15. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche.

    Science.gov (United States)

    Chang, Chiung-Ying; Pasolli, H Amalia; Giannopoulou, Eugenia G; Guasch, Géraldine; Gronostajski, Richard M; Elemento, Olivier; Fuchs, Elaine

    2013-03-07

    Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in

  16. Different Motile Behaviors of Human Hematopoietic Stem versus Progenitor Cells at the Osteoblastic Niche

    Directory of Open Access Journals (Sweden)

    Katie Foster

    2015-11-01

    Full Text Available Despite advances in our understanding of interactions between mouse hematopoietic stem cells (HSCs and their niche, little is known about communication between human HSCs and the microenvironment. Using a xenotransplantation model and intravital imaging, we demonstrate that human HSCs display distinct motile behaviors to their hematopoietic progenitor cell (HPC counterparts, and the same pattern can be found between mouse HSCs and HPCs. HSCs become significantly less motile after transplantation, while progenitor cells remain motile. We show that human HSCs take longer to find their niche than previously expected and suggest that the niche be defined as the position where HSCs stop moving. Intravital imaging is the only technique to determine where in the bone marrow stem cells stop moving, and future analyses should focus on the environment surrounding the HSC at this point.

  17. Prostate cancer cells metastasize to the hematopoietic stem cell niche in bone

    Institute of Scientific and Technical Information of China (English)

    Evan T Keller

    2011-01-01

    @@ The majority of men with advanced prostate cancer develop bone metastases as opposed to metastases at other sites.1 It has been unclear why prostate cancer selectively metastasizes to and proliferates in bone.Recently, Shiozawa et al.Delineated a mechanism that may account for the establishment of prostate cancer in bone.2 Specifically, they identified that prostate cancer cells compete with hematopoietic stem cells (HSC) for the osteoblast in the HSC niche of the bone.Defining the mechanisms through which prostate cancer cells establish themselves in bone is critical towards developing effective therapeutic strategies to prevent or target bone metastases.

  18. Classic and novel stem cell niches in brain homeostasis and repair.

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection.

  19. The Hippo pathway regulates homeostatic growth of stem cell niche precursors in the Drosophila ovary.

    Science.gov (United States)

    Sarikaya, Didem P; Extavour, Cassandra G

    2015-02-01

    The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity.

  20. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.

    Science.gov (United States)

    Tseng, Chen-Yuan; Kao, Shih-Han; Wan, Chih-Ling; Cho, Yueh; Tung, Shu-Yun; Hsu, Hwei-Jan

    2014-12-01

    Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs), and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention) is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.

  1. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.

    Directory of Open Access Journals (Sweden)

    Chen-Yuan Tseng

    2014-12-01

    Full Text Available Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs, and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.

  2. Structural characterization and primary in vitro cell culture of locust male germline stem cells and their niche.

    Science.gov (United States)

    Dorn, David C; Dorn, August

    2011-03-01

    The establishment of in vitro culture systems to expand stem cells and to elucidate the niche/stem cell interaction is among the most sought-after culture systems of our time. To further investigate niche/stem cell interactions, we evaluated in vitro cultures of isolated intact male germline-niche complexes (i.e., apical complexes), complexes with empty niche spaces, and completely empty niches (i.e., isolated apical cells) from the testes of Locusta migratoria and the interaction of these complexes with isolated germline stem cells, spermatogonia (of transit-amplifying stages), cyst progenitor cells, cyst progenitor cell-like cells, cyst cells, and follicle envelope cells. The structural characteristics of these cell types allow the identification of the different cell types in primary cultures, which we studied in detail by light and electron microscopy. In intact testes germline stem cells strongly adhere to their niche (the apical cell), but emigrate from their niche and form filopodia if the apical complex is put into culture with "standard media." The lively movements of the long filopodia of isolated germline stem cells and spermatogonia may be indicative of their search for specific signals to home to their niche. All other incubated cell types (except for follicle envelope cells) expressed rhizopodia and lobopodia. Nevertheless isolated germline stem cells in culture do not migrate to empty niche spaces of nearby apical cells. This could indicate that apical cells lose their germline stem cell attracting ability in vitro, although apical cells devoid of germline stem cells either by emigration of germline stem cells or by mechanical removal of germline stem cells are capable of surviving in vitro up to 56 days, forming many small lobopodia and performing amoeboid movements. We hypothesize that the breakdown of the apical complex in vitro with standard media interrupts the signaling between the germline stem cells and the niche (and conceivably the cyst

  3. Purinergic signalling in a latent stem cell niche of the rat spinal cord.

    Science.gov (United States)

    Marichal, Nicolás; Fabbiani, Gabriela; Trujillo-Cenóz, Omar; Russo, Raúl E

    2016-06-01

    The ependyma of the spinal cord harbours stem cells which are activated by traumatic spinal cord injury. Progenitor-like cells in the central canal (CC) are organized in spatial domains. The cells lining the lateral aspects combine characteristics of ependymocytes and radial glia (RG) whereas in the dorsal and ventral poles, CC-contacting cells have the morphological phenotype of RG and display complex electrophysiological phenotypes. The signals that may affect these progenitors are little understood. Because ATP is massively released after spinal cord injury, we hypothesized that purinergic signalling plays a part in this spinal stem cell niche. We combined immunohistochemistry, in vitro patch-clamp whole-cell recordings and Ca(2+) imaging to explore the effects of purinergic agonists on ependymal progenitor-like cells in the neonatal (P1-P6) rat spinal cord. Prolonged focal application of a high concentration of ATP (1 mM) induced a slow inward current. Equimolar concentrations of BzATP generated larger currents that reversed close to 0 mV, had a linear current-voltage relationship and were blocked by Brilliant Blue G, suggesting the presence of functional P2X7 receptors. Immunohistochemistry showed that P2X7 receptors were expressed around the CC and the processes of RG. BzATP also generated Ca(2+) waves in RG that were triggered by Ca(2+) influx and propagated via Ca(2+) release from internal stores through activation of ryanodine receptors. We speculate that the intracellular Ca(2+) signalling triggered by P2X7 receptor activation may be an epigenetic mechanism to modulate the behaviour of progenitors in response to ATP released after injury.

  4. Stromal-cell and cancer-cell exosomes leading the metastatic exodus for the promised niche.

    Science.gov (United States)

    Hoffman, Robert M

    2013-06-18

    Exosomes are thought to play an important role in metastasis. Luga and colleagues have described the production of exosomes by stromal cells such as cancer-associated fibroblasts that are taken up by breast cancer cells and are then loaded with Wnt 11, which is associated with stimulation of the invasiveness and metastasis of the breast cancer cells. Previous studies have shown that exosomes produced by breast cancer cells are taken up by stromal fibroblasts and other stromal cells, suggesting that exosomes are agents of cross-talk between cancer and stromal cells to stimulate metastasis. Imaging of exosomes by labeling with fluorescent proteins will enlighten the process by which exosomes enhance metastasis, including premetastatic niche formation.

  5. Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes.

    Science.gov (United States)

    Morena, Deborah; Maestro, Nicola; Bersani, Francesca; Forni, Paolo Emanuele; Lingua, Marcello Francesco; Foglizzo, Valentina; Šćepanović, Petar; Miretti, Silvia; Morotti, Alessandro; Shern, Jack F; Khan, Javed; Ala, Ugo; Provero, Paolo; Sala, Valentina; Crepaldi, Tiziana; Gasparini, Patrizia; Casanova, Michela; Ferrari, Andrea; Sozzi, Gabriella; Chiarle, Roberto; Ponzetto, Carola; Taulli, Riccardo

    2016-03-17

    Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity.

  6. A DTC niche plexus surrounds the germline stem cell pool in Caenorhabditis elegans.

    Science.gov (United States)

    Byrd, Dana T; Knobel, Karla; Affeldt, Katharyn; Crittenden, Sarah L; Kimble, Judith

    2014-01-01

    The mesenchymal distal tip cell (DTC) provides the niche for Caenorhabditis elegans germline stem cells (GSCs). The DTC has a complex cellular architecture: its cell body caps the distal gonadal end and contacts germ cells extensively, but it also includes multiple cellular processes that extend along the germline tube and intercalate between germ cells. Here we use the lag-2 DTC promoter to drive expression of myristoylated GFP, which highlights DTC membranes and permits a more detailed view of DTC architecture. We find that short processes intercalating between germ cells contact more germ cells than seen previously. We define this region of extensive niche contact with germ cells as the DTC plexus. The extent of the DTC plexus corresponds well with the previously determined extent of the GSC pool. Moreover, expression of a differentiation marker increases as germ cells move out of the plexus. Maintenance of this DTC plexus depends on the presence of undifferentiated germ cells, suggesting that germ cell state can influence niche architecture. The roles of this DTC architecture remain an open question. One idea is that the DTC plexus delivers Notch signaling to the cluster of germ cells comprising the GSC pool; another idea is that the plexus anchors GSCs at the distal end.

  7. Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent

    Directory of Open Access Journals (Sweden)

    Lisa L. Korn

    2014-12-01

    Full Text Available Regulatory T cells (Tregs are CD4+ T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4+ T cells, Tregs require antigen-specific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII interactions for their development. However, the requirement for MHCII in Treg homeostasis in tissues such as intestinal lamina propria (LP is unknown. We examined LP Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs (iTregs. Thymically generated Tregs entered the LP of weanlings and proliferated independently of MHCII to fill the compartment. The adult LP was a closed niche; new thymic Tregs were excluded, and Tregs in parabiotic pairs were LP resident. The isolated LP niche was interleukin-2 (IL-2 independent but dependent on commensal bacteria. Thus, an LP Treg niche can be filled, isolated, and maintained independently of antigen signals and iTregs. This niche may represent a tissue-specific mechanism for maintaining immune tolerance.

  8. CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche.

    Science.gov (United States)

    Yokohama-Tamaki, Tamaki; Otsu, Keishi; Harada, Hidemitsu; Shibata, Shunichi; Obara, Nobuko; Irie, Kazuharu; Taniguchi, Akiyoshi; Nagasawa, Takashi; Aoki, Kazunari; Caliari, Steven R; Weisgerber, Daniel W; Harley, Brendan A C

    2015-12-01

    Dental stem cells are located at the proximal ends of rodent incisors. These stem cells reside in the dental epithelial stem cell niche, termed the apical bud. We focused on identifying critical features of a chemotactic signal in the niche. Here, we report that CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in dental stem cell niche cells. We report cells in the apical bud express CXCR4 mRNA at high levels while expression is restricted in the basal epithelium (BE) and transit-amplifying (TA) cell regions. Furthermore, the CXCL12 ligand is present in mesenchymal cells adjacent to the apical bud. We then performed gain- and loss-of-function analyses to better elucidate the role of CXCR4 and CXCL12. CXCR4-deficient mice contain epithelial cell aggregates, while cell proliferation in mutant incisors was also significantly reduced. We demonstrate in vitro that dental epithelial cells migrate toward sources of CXCL12, whereas knocking down CXCR4 impaired motility and resulted in formation of dense cell colonies. These results suggest that CXCR4 expression may be critical for activation of enamel progenitor cell division and that CXCR4/CXCL12 signaling may control movement of epithelial progenitors from the dental stem cell niche.

  9. Type 1 collagen as a potential niche component for CD133-positive glioblastoma cells.

    Science.gov (United States)

    Motegi, Hiroaki; Kamoshima, Yuuta; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Houkin, Kiyohiro

    2014-08-01

    Cancer stem cells are thought to be closely related to tumor progression and recurrence, making them attractive therapeutic targets. Stem cells of various tissues exist within niches maintaining their stemness. Glioblastoma stem cells (GSCs) are located at tumor capillaries and the perivascular niche, which are considered to have an important role in maintaining GSCs. There were some extracellular matrices (ECM) on the perivascular connective tissue, including type 1 collagen. We here evaluated whether type 1 collagen has a potential niche for GSCs. Imunohistochemical staining of type 1 collagen and CD133, one of the GSCs markers, on glioblastoma (GBM) tissues showed CD133-positive cells were located in immediate proximity to type 1 collagen around tumor vessels. We cultured human GBM cell lines, U87MG and GBM cells obtained from fresh surgical tissues, T472 and T555, with serum-containing medium (SCM) or serum-free medium with some growth factors (SFM) and in non-coated (Non-coat) or type 1 collagen-coated plates (Col). The RNA expression levels of CD133 and Nestin as stem cell markers in each condition were examined. The Col condition not only with SFM but SCM made GBM cells more enhanced in RNA expression of CD133, compared to Non-coat/SCM. Semi-quantitative measurement of CD133-positive cells by immunocytochemistry showed a statistically significant increase of CD133-positive cells in Col/SFM. In addition, T472 cell line cultured in the Col/SFM had capabilities of sphere formation and tumorigenesis. Type 1 collagen was found in the perivascular area and showed a possibility to maintain GSCs. These findings suggest that type 1 collagen could be one important niche component for CD133-positive GSCs and maintain GSCs in adherent culture.

  10. Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

    Directory of Open Access Journals (Sweden)

    Heather A. Himburg

    2012-10-01

    Full Text Available The mechanisms through which the bone marrow (BM microenvironment regulates hematopoietic stem cell (HSC fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN in regulating HSC function in the niche. PTN−/− mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.

  11. The spermatogonial stem cell niche in the collared peccary (Tayassu tajacu).

    Science.gov (United States)

    Campos-Junior, Paulo Henrique A; Costa, Guilherme M J; Lacerda, Samyra M S N; Rezende-Neto, José V; de Paula, Ana M; Hofmann, Marie-Claude; de França, Luiz R

    2012-05-01

    In the seminiferous epithelium, spermatogonial stem cells (SSCs) are located in a particular environment called the "niche" that is controlled by the basement membrane, key testis somatic cells, and factors originating from the vascular network. However, the role of Leydig cells (LCs) as a niche component is not yet clearly elucidated. Recent studies showed that peccaries (Tayassu tajacu) present a peculiar LC cytoarchitecture in which these cells are located around the seminiferous tubule lobes, making the peccary a unique model for investigating the SSC niche. This peculiarity allowed us to subdivide the seminiferous tubule cross-sections in three different testis parenchyma regions (tubule-tubule, tubule-interstitium, and tubule-LC contact). Our aims were to characterize the different spermatogonial cell types and to determine the location and/or distribution of the SSCs along the seminiferous tubules. Compared to differentiating spermatogonia, undifferentiated spermatogonia (A(und)) presented a noticeably higher nuclear volume (P < 0.05), allowing an accurate evaluation of their distribution. Immunostaining analysis demonstrated that approximately 93% of A(und) were GDNF receptor alpha 1 positive (GFRA1(+)), and these cells were preferentially located adjacent to the interstitial compartment without LCs (P < 0.05). The expression of colony-stimulating factor 1 was observed in LCs and peritubular myoid cells (PMCs), whereas its receptor was present in LCs and in GFRA1(+) A(und). Taken together, our findings strongly suggest that LCs, different from PMCs, might play a minor role in the SSC niche and physiology and that these steroidogenic cells are probably involved in the differentiation of A(und) toward type A(1) spermatogonia.

  12. Elucidating the Tumor-Suppressive Role of SLITs in Maintaining the Basal Cell Niche

    Science.gov (United States)

    2011-10-01

    of both the glandular epithelium and vasculature and promotes metastasis formation. Int J Oncol. 2009;35(3):525–36. 10. Marlow R, Strickland P, Lee JS...organize tissue structure, including cells in the breast stem cell niche, and to generate the barrier between epithelium and stroma by secreting the...Macias H., Cardiff R.D., Sukumar S., Hinck. 2008. SLITs suppress tumor growth and microenvironment by silencing Sdf1/Cxcr4 within breast epithelium

  13. Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Luciana Teofili

    2015-05-01

    Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

  14. Stem Cell Niche, the Microenvironment and Immunological Crosstalk

    Institute of Scientific and Technical Information of China (English)

    Law Sujata; S. Chaudhuri

    2008-01-01

    The concept of stem cells, their physiological existence, the intricate anatomical localization, the known and the unknown functions, and their exclusive utility for the purpose of regenerative medicine, are all now encompassed within an emergent question, 'how compatible these cells are immunologically?'Indeed, the medical aspects of stem cells are dependent on a large number of queries based on the basic properties of the cells. It has greatly been emphasized to probe into the basic research on stem cells before any successful therapeutic attempts are made. One of the intricate aspects of the adult stem cells is its immunological behavior in relation to the microenvironmental associates, the stromal ceils in the presence of a suitable target.

  15. Reversible neural stem cell niche dysfunction in a model of multiple sclerosis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Imitola, Jaime; Ayuso-Sacido, Angel;

    2011-01-01

    OBJECTIVE: The subventricular zone (SVZ) of the brain constitutes a niche for neural stem and progenitor cells that can initiate repair after central nervous system (CNS) injury. In a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE), the neural stem cells (NSCs) become...... with minocycline, an inhibitor of microglia activation, increases stem cell proliferation in both naive and EAE animals. Minocycline treatment decreases cortical and periventricular pathology in the chronic phase of EAE, improving the proliferation of Sox2 stem cells and NG2 oligodendrocyte precursors cells...

  16. Label-free screening of niche-to-niche variation in satellite stem cells using functionalized pores

    Science.gov (United States)

    Chapman, Matthew R.; Balakrishnan, Karthik; Conboy, Michael J.; Mohanty, Swomitra; Jabart, Eric; Huang, Haiyan; Hack, James; Conboy, Irina M.; Sohn, Lydia L.

    2012-02-01

    Combinations of surface markers are currently used to identify muscle satellite cells. Using pores functionalized with specific antibodies and measuring the transit time of cells passing through these pores, we discovered remarkable heterogeneity in the expression of these markers in muscle (satellite) stem cells that reside in different single myofibers. Microniche-specific variation in stem cells of the same organ has not been previously described, as bulk analysis does not discriminate between separate myofibers or even separate hind-leg muscle groups. We found a significant population of Sca-1+ satellite cells that form myotubes, thereby demonstrating the myogenic potential of Sca-1+ cells, which are currently excluded in bulk sorting. Finally, using our label-free pore screening technique, we have been able to quantify directly surface expression of Notch1 without activation of the Notch pathway. We show for the first time Notch1-expression heterogeneity in unactivated satellite cells. The discovery of fiber-to-fiber variations prompts new research into the reasons for such diversity in muscle stem cells.

  17. The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration.

    Science.gov (United States)

    Chen, Chih-Chiang; Plikus, Maksim V; Tang, Pin-Chi; Widelitz, Randall B; Chuong, Cheng Ming

    2016-04-10

    Hair and feathers are unique because (1) their stem cells are contained within a follicle structure, (2) they undergo cyclic regeneration repetitively throughout life, (3) regeneration occurs physiologically in healthy individuals and (4) regeneration is also induced in response to injury. Precise control of this cyclic regeneration process is essential for maintaining the homeostasis of living organisms. While stem cells are regulated by the intra-follicle-adjacent micro-environmental niche, this niche is also modulated dynamically by extra-follicular macro-environmental signals, allowing stem cells to adapt to a larger changing environment and physiological needs. Here we review several examples of macro-environments that communicate with the follicles: intradermal adipose tissue, innate immune system, sex hormones, aging, circadian rhythm and seasonal rhythms. Related diseases are also discussed. Unveiling the mechanisms of how stem cell niches are modulated provides clues for regenerative medicine. Given that stem cells are hard to manipulate, focusing translational therapeutic applications at the environments appears to be a more practical approach.

  18. Mesenchymal Stem Cells Secretome as a Modulator of the Neurogenic Niche: Basic Insights and Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    Antonio eSalgado

    2015-07-01

    Full Text Available Neural stem cells (NSCs and mesenchymal stem cells (MSCs share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g bone and central nervous system that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF, glial derived neurotrophic factor (GDNF, and brain derived neurotrophic factor (BDNF, among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.

  19. Predicting the current and future potential distributions of lymphatic filariasis in Africa using maximum entropy ecological niche modelling.

    Science.gov (United States)

    Slater, Hannah; Michael, Edwin

    2012-01-01

    Modelling the spatial distributions of human parasite species is crucial to understanding the environmental determinants of infection as well as for guiding the planning of control programmes. Here, we use ecological niche modelling to map the current potential distribution of the macroparasitic disease, lymphatic filariasis (LF), in Africa, and to estimate how future changes in climate and population could affect its spread and burden across the continent. We used 508 community-specific infection presence data collated from the published literature in conjunction with five predictive environmental/climatic and demographic variables, and a maximum entropy niche modelling method to construct the first ecological niche maps describing potential distribution and burden of LF in Africa. We also ran the best-fit model against climate projections made by the HADCM3 and CCCMA models for 2050 under A2a and B2a scenarios to simulate the likely distribution of LF under future climate and population changes. We predict a broad geographic distribution of LF in Africa extending from the west to the east across the middle region of the continent, with high probabilities of occurrence in the Western Africa compared to large areas of medium probability interspersed with smaller areas of high probability in Central and Eastern Africa and in Madagascar. We uncovered complex relationships between predictor ecological niche variables and the probability of LF occurrence. We show for the first time that predicted climate change and population growth will expand both the range and risk of LF infection (and ultimately disease) in an endemic region. We estimate that populations at risk to LF may range from 543 and 804 million currently, and that this could rise to between 1.65 to 1.86 billion in the future depending on the climate scenario used and thresholds applied to signify infection presence.

  20. Predicting the current and future potential distributions of lymphatic filariasis in Africa using maximum entropy ecological niche modelling.

    Directory of Open Access Journals (Sweden)

    Hannah Slater

    Full Text Available Modelling the spatial distributions of human parasite species is crucial to understanding the environmental determinants of infection as well as for guiding the planning of control programmes. Here, we use ecological niche modelling to map the current potential distribution of the macroparasitic disease, lymphatic filariasis (LF, in Africa, and to estimate how future changes in climate and population could affect its spread and burden across the continent. We used 508 community-specific infection presence data collated from the published literature in conjunction with five predictive environmental/climatic and demographic variables, and a maximum entropy niche modelling method to construct the first ecological niche maps describing potential distribution and burden of LF in Africa. We also ran the best-fit model against climate projections made by the HADCM3 and CCCMA models for 2050 under A2a and B2a scenarios to simulate the likely distribution of LF under future climate and population changes. We predict a broad geographic distribution of LF in Africa extending from the west to the east across the middle region of the continent, with high probabilities of occurrence in the Western Africa compared to large areas of medium probability interspersed with smaller areas of high probability in Central and Eastern Africa and in Madagascar. We uncovered complex relationships between predictor ecological niche variables and the probability of LF occurrence. We show for the first time that predicted climate change and population growth will expand both the range and risk of LF infection (and ultimately disease in an endemic region. We estimate that populations at risk to LF may range from 543 and 804 million currently, and that this could rise to between 1.65 to 1.86 billion in the future depending on the climate scenario used and thresholds applied to signify infection presence.

  1. A GRFa2/Prop1/stem (GPS cell niche in the pituitary.

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    Montse Garcia-Lavandeira

    Full Text Available BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the

  2. Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization

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    Yaiza del Pozo Martin

    2015-12-01

    Full Text Available During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2 expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-β-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization.

  3. Long-term homeostasis and wound healing in an in vitro epithelial stem cell niche model

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    Miyashita, Hideyuki; Niwano, Hiroko; Yoshida, Satoru; Hatou, Shin; Inagaki, Emi; Tsubota, Kazuo; Shimmura, Shigeto

    2017-01-01

    Cultures of epithelial cells are limited by the proliferative capacity of primary cells and cell senescence. Herein we show that primary human epithelial cell sheets cultured without dermal equivalents maintained homeostasis in vitro for at least 1 year. Transparency of these sheets enabled live observation of pigmented melanocytes and Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) labeled epithelial cells during wound healing. Cell turn over and KRT15 expression pattern stabilized within 3 months, when KRT15 bright clusters often associated with niche-like melanocytes became apparent. EdU labels were retained in a subset of epithelial cells and melanocytes after 6 months chasing, suggesting their slow cell cycling property. FUCCI-labeling demonstrated robust cell migration and proliferation following wounding. Transparency and long-term (1 year) homeostasis of this model will be a powerful tool for the study of wound healing and cell linage tracing. PMID:28233843

  4. Stem cell decisions: a twist of fate or a niche market?

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    Januschke, Jens; Näthke, Inke

    2014-10-01

    Establishing and maintaining cell fate in the right place at the right time is a key requirement for normal tissue maintenance. Stem cells are at the core of this process. Understanding how stem cells balance self-renewal and production of differentiating cells is key for understanding the defects that underpin many diseases. Both, external cues from the environment and cell intrinsic mechanisms can control the outcome of stem cell division. The role of the orientation of stem cell division has emerged as an important mechanism for specifying cell fate decisions. Although, the alignment of cell divisions can dependent on spatial cues from the environment, maintaining stemness is not always linked to positioning of stem cells in a particular microenvironment or `niche'. Alternate mechanisms that could contribute to cellular memory include differential segregation of centrosomes in asymmetrically dividing cells.

  5. Human peripheral blood-born hematosphere as a niche for hematopoietic stem cell expansion

    Institute of Scientific and Technical Information of China (English)

    Jin Hur; Eun Ju Lee; Hyun-Jai Cho; Hyun-Jae Kang; Byung-Hee Oh; Young-Bae Park; Hyo-Soo Kim; Jonghanne Park; Sang Eun Lee; Chang-Hwan Yoon; Jae Hee Jang; Ji Min Yang; Tae-Kyu Lee; Jae-Il Choi; Han-Mo Yang

    2011-01-01

    @@ Dear Editor, Transplantation of autologous hematopoietic stem/progenitor cells (HSPCs) derived from the adult peripheral blood has been widely used in the treatment of various hematological diseases [1].However,the small number of circulating HSPC is the major limitation and necessitates additional interventions such as G-CSF mobilization and leukapheresis.There have been several attempts to overcome the limitation with ex vivo expansion of HSPC.These strategies are largely based on supplementation of one or more "stem cell niche components"such as supporting-cells,growth factors,extracellular matrix (ECM) or physicochemical microenvironment in the bone marrow [2].Spheroid culture methods of stem ceils from different tissues have been successfully used for expansion of cardiac and neural stem cells.These spheres sensitize target stem cells to growth factors and provide sufficient cell-to-cell and cell-to-matrix contacts,mimicking the in vivo stem cell niche [3,4].Here we asked whether spheroid culture of blood mononuclear cells (MNCs) would potentiate the expansion of circulating blood HSPC.

  6. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

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    Baer, Caroline; Squadrito, Mario Leonardo [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Iruela-Arispe, M. Luisa, E-mail: arispe@mcdb.ucla.edu [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles 90095, CA (United States); De Palma, Michele, E-mail: michele.depalma@epfl.ch [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland)

    2013-07-01

    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches.

  7. The Spermatogonial Stem Cell Niche in the Collared Peccary (Tayassu tajacu)1

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    Campos-Junior, Paulo Henrique A.; Costa, Guilherme M.J.; Lacerda, Samyra M.S.N.; Rezende-Neto, José V.; de Paula, Ana M.; Hofmann, Marie-Claude; de França, Luiz R.

    2012-01-01

    ABSTRACT In the seminiferous epithelium, spermatogonial stem cells (SSCs) are located in a particular environment called the “niche” that is controlled by the basement membrane, key testis somatic cells, and factors originating from the vascular network. However, the role of Leydig cells (LCs) as a niche component is not yet clearly elucidated. Recent studies showed that peccaries (Tayassu tajacu) present a peculiar LC cytoarchitecture in which these cells are located around the seminiferous tubule lobes, making the peccary a unique model for investigating the SSC niche. This peculiarity allowed us to subdivide the seminiferous tubule cross-sections in three different testis parenchyma regions (tubule-tubule, tubule-interstitium, and tubule-LC contact). Our aims were to characterize the different spermatogonial cell types and to determine the location and/or distribution of the SSCs along the seminiferous tubules. Compared to differentiating spermatogonia, undifferentiated spermatogonia (Aund) presented a noticeably higher nuclear volume (P < 0.05), allowing an accurate evaluation of their distribution. Immunostaining analysis demonstrated that approximately 93% of Aund were GDNF receptor alpha 1 positive (GFRA1+), and these cells were preferentially located adjacent to the interstitial compartment without LCs (P < 0.05). The expression of colony-stimulating factor 1 was observed in LCs and peritubular myoid cells (PMCs), whereas its receptor was present in LCs and in GFRA1+ Aund. Taken together, our findings strongly suggest that LCs, different from PMCs, might play a minor role in the SSC niche and physiology and that these steroidogenic cells are probably involved in the differentiation of Aund toward type A1 spermatogonia. PMID:22262689

  8. Cancer Microenvironment: What Can We Learn from the Stem Cell Niche.

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    Lacina, Lukas; Plzak, Jan; Kodet, Ondrej; Szabo, Pavol; Chovanec, Martin; Dvorankova, Barbora; Smetana, Karel

    2015-10-12

    Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle-also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.

  9. Cancer Microenvironment: What Can We Learn from the Stem Cell Niche

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    Lukas Lacina

    2015-10-01

    Full Text Available Epidermal stem cells (ESCs are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle—also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs. This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.

  10. Rab8a vesicles regulate Wnt ligand delivery and Paneth cell maturation at the intestinal stem cell niche.

    Science.gov (United States)

    Das, Soumyashree; Yu, Shiyan; Sakamori, Ryotaro; Vedula, Pavan; Feng, Qiang; Flores, Juan; Hoffman, Andrew; Fu, Jiang; Stypulkowski, Ewa; Rodriguez, Alexis; Dobrowolski, Radek; Harada, Akihiro; Hsu, Wei; Bonder, Edward M; Verzi, Michael P; Gao, Nan

    2015-06-15

    Communication between stem and niche supporting cells maintains the homeostasis of adult tissues. Wnt signaling is a crucial regulator of the stem cell niche, but the mechanism that governs Wnt ligand delivery in this compartment has not been fully investigated. We identified that Wnt secretion is partly dependent on Rab8a-mediated anterograde transport of Gpr177 (wntless), a Wnt-specific transmembrane transporter. Gpr177 binds to Rab8a, depletion of which compromises Gpr177 traffic, thereby weakening the secretion of multiple Wnts. Analyses of generic Wnt/β-catenin targets in Rab8a knockout mouse intestinal crypts indicate reduced signaling activities; maturation of Paneth cells - a Wnt-dependent cell type - is severely affected. Rab8a knockout crypts show an expansion of Lgr5(+) and Hopx(+) cells in vivo. However, in vitro, the knockout enteroids exhibit significantly weakened growth that can be partly restored by exogenous Wnts or Gsk3β inhibitors. Immunogold labeling and surface protein isolation identified decreased plasma membrane localization of Gpr177 in Rab8a knockout Paneth cells and fibroblasts. Upon stimulation by exogenous Wnts, Rab8a-deficient cells show ligand-induced Lrp6 phosphorylation and transcriptional reporter activation. Rab8a thus controls Wnt delivery in producing cells and is crucial for Paneth cell maturation. Our data highlight the profound tissue plasticity that occurs in response to stress induced by depletion of a stem cell niche signal.

  11. Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Michael J Nemeth; David M Bodine

    2007-01-01

    Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal (in which the ability to function as HSCs is retained) and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the "niche", focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.

  12. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche.

    Science.gov (United States)

    Erler, Janine T; Bennewith, Kevin L; Cox, Thomas R; Lang, Georgina; Bird, Demelza; Koong, Albert; Le, Quynh-Thu; Giaccia, Amato J

    2009-01-06

    Tumor cell metastasis is facilitated by "premetastatic niches" formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for premetastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at premetastatic sites, crosslinks collagen IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to crosslinked collagen IV and produce matrix metalloproteinase-2, which cleaves collagen, enhancing the invasion and recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents CD11b+ cell recruitment and metastatic growth. CD11b+ cells and LOX also colocalize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in premetastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease.

  13. Gastrointestinal stem cells. III. Emergent themes of liver stem cell biology: niche, quiescence, self-renewal, and plasticity.

    Science.gov (United States)

    Theise, Neil D

    2006-02-01

    This essay will address areas of liver stem/progenitor cell studies in which consensus has emerged and in which controversy still prevails over consensus, but it will also highlight important themes that inevitably should be a focus of liver stem/progenitor cell investigations in coming years. Thus concepts regarding cell plasticity, the existence of a physiological/anatomic stem cell niche, and whether intrahepatic liver stem/progenitor cells comprise true stem cells or progenitor cells (or both) will be approached in some detail.

  14. Osteogenic and neurogenic stem cells in their own place: unraveling differences and similarities between niches

    Directory of Open Access Journals (Sweden)

    Wanda eLattanzi

    2015-11-01

    Full Text Available Although therapeutic use of stem cells is already available in some tissues (cornea, blood, skin, in most organs we are far from reaching the translational goal of regenerative medicine. In the nervous system, due to intrinsic features which make it refractory to regeneration/repair,it is very hard to obtainfunctionally-integrated regenerative outcomes, evenstarting from its own stem cells(the neural stem cells; NSCs. Besides NSCs, mesenchymal stem cells (MSCs have also been proposed for therapeutic purposes in neurological diseases. Yet, direct (regenerative and indirect (bystander effects are often confused, as are MSCs and bone marrow-derived (stromal, osteogenic stem cells (BMSCs, whoseplasticity isactually overestimated (i.e. trans-differentiation along non-mesodermal lineages, including neural fates.In order to better understand failure in the regenerative use of stem cells for neurological disorders,it could be helpful to understand how NSCs and BMSCs have adapted to their respective organ niches. In this perspective, here the adult osteogenic and neurogenic niches are considered and compared within their in vivo environment.

  15. Molecular characterization of retinal stem cells and their niches in adult zebrafish

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    Barthel Linda K

    2006-07-01

    Full Text Available Abstract Background The persistence in adult teleost fish of retinal stem cells that exhibit all of the features of true 'adult stem cells' – self-renewal, multipotency, and the capacity to respond to injury by mitotic activation with the ability to regenerate differentiated tissues – has been known for several decades. However, the specialized cellular and molecular characteristics of these adult retinal stem cells and the microenvironmental niches that support their maintenance in the differentiated retina and regulate their activity during growth and regeneration have not yet been elucidated. Results Our data show that the zebrafish retina has two kinds of specialized niches that sustain retinal stem cells: 1 a neuroepithelial germinal zone at the interface between neural retina and ciliary epithelium, called the ciliary marginal zone (CMZ, a continuous annulus around the retinal circumference, and 2 the microenvironment around some Müller glia in the differentiated retina. In the uninjured retina, scattered Müller glia (more frequently those in peripheral retina are associated with clusters of proliferating retinal progenitors that are restricted to the rod photoreceptor lineage, but following injury, the Müller-associated retinal progenitors can function as multipotent retinal stem cells to regenerate other types of retinal neurons. The CMZ has several features in common with the neurogenic niches in the adult mammalian brain, including access to the apical epithelial surface and a close association with blood vessels. Müller glia in the teleost retina have a complex response to local injury that includes some features of reactive gliosis (up-regulation of glial fibrillary acidic protein, GFAP, and re-entry into the cell cycle together with dedifferentiation and re-acquisition of phenotypic and molecular characteristics of multipotent retinal progenitors in the CMZ (diffuse distribution of N-cadherin, activation of Notch

  16. Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver.

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    Iwasaki, Hiroko; Arai, Fumio; Kubota, Yoshiaki; Dahl, Maria; Suda, Toshio

    2010-07-29

    Hematopoietic stem cells (HSCs) are maintained in specialized niches in adult bone marrow. However, niche and HSC maintenance mechanism in fetal liver (FL) still remains unclear. Here, we investigated the niche and the molecular mechanism of HSC maintenance in mouse FL using HSCs expressing endothelial protein C receptor (EPCR). The antiapoptotic effect of activated protein C (APC) on EPCR(+) HSCs and the expression of protease-activated receptor 1 (Par-1) mRNA in these cells suggested the involvement of the cytoprotective APC/EPCR/Par-1 pathway in HSC maintenance. Immunohistochemistry revealed that EPCR(+) cells were localized adjacent to, or integrated in, the Lyve-1(+) sinusoidal network, where APC and extracellular matrix (ECM) are abundant, suggesting that HSCs in FL were maintained in the APC- and ECM-rich perisinusoidal niche. EPCR(+) HSCs were in a relatively slow cycling state, consistent with their high expression levels of p57 and p18. Furthermore, the long-term reconstitution activity of EPCR(+) HSCs decreased significantly after short culture but not when cocultured with feeder layer of FL-derived Lyve-1(+) cells, which suggests that the maintenance of the self-renewal activity of FL HSCs largely depended on the interaction with the perisinusoidal niche. In conclusion, EPCR(+) HSCs resided in the perisinusoidal niche in mouse FL.

  17. Notch signaling pathway and glioma stem cell niche%Notch信号通路与脑胶质瘤干细胞的niche

    Institute of Scientific and Technical Information of China (English)

    林才厚; 郑宗清; 邱献新; 林志雄

    2013-01-01

    A small fraction of tumor stem cells exist in glioma and play a key role in the tumorigenesis and propagation of glioma.They have a close relationship with their niche that offers structural and functional support.In glioma niche,vascular endothelial cells can provide Notch ligands for cancer stem cells to activate Notch signaling pathway and contact with other signaling pathways,maintaining the tumor stem cell self-renewal and increasing resistance of brain tumor stem cells to radiotherapy.Therefore,Notch signaling pathway is considered to be a new therapeutic target of glioma.%研究表明极少数量肿瘤干细胞存在于脑胶质瘤中,但在其发生发展中起关键作用.脑胶质瘤干细胞与为其提供结构和功能支持的血管niche关系密切.在脑胶质瘤niche中,血管内皮细胞可以提供Notch配体给肿瘤干细胞,激活Notch信号通路,并与其他信号通路构成串话,维持肿瘤干细胞的自我更新,增加脑肿瘤干细胞对放疗的抵抗性.因此,Notch信号通路被认为是脑胶质瘤新的治疗靶点.

  18. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

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    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  19. Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.

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    Richard C van der Wath

    Full Text Available The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2-3 days in mice (3-5 days in humans and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the 'pedigree' and the 'niche' models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.

  20. Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

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    Ingrid R. Cordeiro

    2015-09-01

    Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

  1. Genetic basis for developmental homeostasis of germline stem cell niche number: a network of Tramtrack-Group nuclear BTB factors.

    Directory of Open Access Journals (Sweden)

    Mathieu Bartoletti

    Full Text Available The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs, each made of 8-10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches.

  2. Genetic basis for developmental homeostasis of germline stem cell niche number: a network of Tramtrack-Group nuclear BTB factors.

    Science.gov (United States)

    Bartoletti, Mathieu; Rubin, Thomas; Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

    2012-01-01

    The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8-10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches.

  3. Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation.

    Science.gov (United States)

    Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P

    2017-02-01

    Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These two cell types demonstrate similar effects in promoting the compaction and cell spreading, as well as expression of maturation markers at both gene and protein levels. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of twitch force, elastic modulus, sarcomere length and molecular signature, when comparing to static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture. Our results therefore suggest that this 3D model can be used for in vitro cardiac maturation study.

  4. SOX9: a stem cell transcriptional regulator of secreted niche signaling factors.

    Science.gov (United States)

    Kadaja, Meelis; Keyes, Brice E; Lin, Mingyan; Pasolli, H Amalia; Genander, Maria; Polak, Lisa; Stokes, Nicole; Zheng, Deyou; Fuchs, Elaine

    2014-02-15

    Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs) at the base of the resting follicle. HF-SC formation occurs during HF development and requires transcription factor SOX9. Whether and how SOX9 functions in HF-SC maintenance remain unknown. By conditionally targeting Sox9 in adult HF-SCs, we show that SOX9 is essential for maintaining them. SOX9-deficient HF-SCs still transition from quiescence to proliferation and launch the subsequent hair cycle. However, once activated, bulge HF-SCs begin to differentiate into epidermal cells, which naturally lack SOX9. In addition, as HF-SC numbers dwindle, outer root sheath production is not sustained, and HF downgrowth arrests prematurely. Probing the mechanism, we used RNA sequencing (RNA-seq) to identify SOX9-dependent transcriptional changes and chromatin immunoprecipitation (ChIP) and deep sequencing (ChIP-seq) to identify SOX9-bound genes in HF-SCs. Intriguingly, a large cohort of SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Moreover, compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. Overall, our findings reveal roles for SOX9 in regulating adult HF-SC maintenance and suppressing epidermal differentiation in the niche. In addition, our studies expose a role for SCs in coordinating their own behavior in part through non-cell-autonomous signaling within the niche.

  5. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  6. Fetal stromal niches enhance human embryonic stem cell-derived hematopoietic differentiation and globin switch.

    Science.gov (United States)

    Lee, King Yiu; Fong, Benny Shu Pan; Tsang, Kam Sze; Lau, Tze Kin; Ng, Pak Cheung; Lam, Audrey Carmen; Chan, Kathy Yuen Yee; Wang, Chi Chiu; Kung, Hsiang Fu; Li, Chi Kong; Li, Karen

    2011-01-01

    Hematopoiesis during mammalian embryonic development has been perceived as a migratory phenomenon, from the yolk sac blood island to the aorta-gonad-mesonephros (AGM) region, fetal liver (FL), and subsequently, the fetal bone marrow. In this study, we investigated the effects of primary stromal cells from fetal hematopoietic niches and their conditioned media (CM), applied singly or in sequential orders, on induction of human embryonic stem cells, H1, H9, and H14 lines, to hematopoietic cells. Our results demonstrated that stromal support of FL, AGM + FL, and AGM + FL + fetal bone marrow significantly increased the proliferation of embryoid bodies (EB) at day 18 of hematopoietic induction in the presence of thrombopoietin, stem cell factor, and Flt-3 ligand. AGM + FL also increased hematopoietic colony-forming unit (CFU) formation. CM did not enhance EB proliferation but CM of FL and AGM + FL significantly increased the density of total CFU and early erythroid (burst-forming unit) progenitors. Increased commitment to the hematopoietic lineage was demonstrated by enhanced expressions of CD45, alpha-, beta-, and gamma-globins in CFU at day 32, compared with EB at day 18. CM of FL significantly increased these globin expressions, indicating enhanced switches from embryonic to fetal and adult erythropoiesis. Over 50% and 10% of cells derived from CFU expressed CD45 and beta-globin proteins, respectively. Expressions of hematopoietic regulatory genes (Bmi-1, β-Catenin, Hox B4, GATA-1) were increased in EB or CFU cultures supported by FL or sequential CM. Our study has provided a strategy for derivation of hematopoietic cells from embryonic stem cells under the influence of primary hematopoietic niches and CM, particularly the FL.

  7. Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance

    Directory of Open Access Journals (Sweden)

    Alessia Fidoamore

    2016-01-01

    Full Text Available Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.

  8. Outsmart tumor exosomes to steal the cancer initiating cell its niche.

    Science.gov (United States)

    Thuma, Florian; Zöller, Margot

    2014-10-01

    Exosomes are small vesicles that derive from endosomes and are delivered by many cells, including tumor cells that are a particular rich source of exosomes. Exosomes are suggested to be the most potent intercellular communicators. Being recovered in all body fluids, they can communicate with neighboring as well as distant cells. The latter was first described for dendritic cell exosomes that can initiate T cell activation. However, tumor exosomes (TEX) may impede this crosstalk. Besides with hematopoietic cells, TEX communicate with the tumor cell itself, but also with host stroma cells and endothelial cells. This crosstalk received much attention as there is strong evidence that TEX account for angiogenesis and premetastatic niche formation, which may proceed directly via binding and uptake of TEX by cells in the premetastatic organ or indirectly via TEX being taken up by hematopoietic progenitors in the bone marrow (BM), which mature toward lineages with immunosuppressive features or are forced toward premature release from the BM and homing into premetastatic organs. Knowing these deleterious activities of TEX, it becomes demanding to search for modes of therapeutic interference. I here introduce our hypothesis that metastasis formation may be hampered by tailored exosomes that outsmart TEX. The essential prerequisites are an in depth knowledge on TEX binding, uptake, binding-initiated signal transduction and uptake-promoted target cell reprogramming.

  9. Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia:Yin and Yang

    Institute of Scientific and Technical Information of China (English)

    Hong-Sheng Zhou; Bing Z Carter; Michael Andreeff

    2016-01-01

    Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy-induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDF1/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

  10. A niche-based framework to assess current monitoring of European forest birds and guide indicator species' selection.

    Science.gov (United States)

    Wade, Amy S I; Barov, Boris; Burfield, Ian J; Gregory, Richard D; Norris, Ken; Vorisek, Petr; Wu, Taoyang; Butler, Simon J

    2014-01-01

    Concern that European forest biodiversity is depleted and declining has provoked widespread efforts to improve management practices. To gauge the success of these actions, appropriate monitoring of forest ecosystems is paramount. Multi-species indicators are frequently used to assess the state of biodiversity and its response to implemented management, but generally applicable and objective methodologies for species' selection are lacking. Here we use a niche-based approach, underpinned by coarse quantification of species' resource use, to objectively select species for inclusion in a pan-European forest bird indicator. We identify both the minimum number of species required to deliver full resource coverage and the most sensitive species' combination, and explore the trade-off between two key characteristics, sensitivity and redundancy, associated with indicators comprising different numbers of species. We compare our indicator to an existing forest bird indicator selected on the basis of expert opinion and show it is more representative of the wider community. We also present alternative indicators for regional and forest type specific monitoring and show that species' choice can have a significant impact on the indicator and consequent projections about the state of the biodiversity it represents. Furthermore, by comparing indicator sets drawn from currently monitored species and the full forest bird community, we identify gaps in the coverage of the current monitoring scheme. We believe that adopting this niche-based framework for species' selection supports the objective development of multi-species indicators and that it has good potential to be extended to a range of habitats and taxa.

  11. The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse

    Directory of Open Access Journals (Sweden)

    Mancardi Gianluigi

    2007-03-01

    Full Text Available Abstract Background The hematopoietic stem cells (HSCs niche of the bone marrow is comprised of HSCs, osteoblasts, endothelial cells and a stromal component of non-hematopoietic multipotent cells of mesenchymal origin named "mesenchymal stem cells" (MSCs. Results Here we studied the global transcriptional profile of murine MSCs with immuno-therapeutic potential and compared it with that of 486 publicly available microarray datasets from 12 other mouse tissues or cell types. Principal component analysis and hierarchical clustering identified a unique pattern of gene expression capable of distinctively classifying MSCs from other tissues and cells. We then performed an analysis aimed to identify absolute and relative abundance of transcripts in all cell types. We found that the set of transcripts uniquely expressed by MSCs is enriched in transcription factors and components of the Wnt signaling pathway. The analysis of differentially expressed genes also identified a set of genes specifically involved in the HSC niche and is complemented by functional studies that confirm the findings. Interestingly, some of these genes play a role in the maintenance of HSCs in a quiescent state supporting their survival and preventing them from proliferating and differentiating. We also show that MSCs modulate T cell functions in vitro and, upon in vivo administration, ameliorate experimental autoimmune encephalomyelitis (EAE. Conclusion Altogether, these findings provide novel and important insights on the mechanisms of T cell function regulation by MSCs and help to cement the rationale for their application in the treatment of autoimmune diseases.

  12. Current and future niche of North and Central American sand flies (Diptera: psychodidae) in climate change scenarios.

    Science.gov (United States)

    Moo-Llanes, David; Ibarra-Cerdeña, Carlos N; Rebollar-Téllez, Eduardo A; Ibáñez-Bernal, Sergio; González, Camila; Ramsey, Janine M

    2013-01-01

    Ecological niche models are useful tools to infer potential spatial and temporal distributions in vector species and to measure epidemiological risk for infectious diseases such as the Leishmaniases. The ecological niche of 28 North and Central American sand fly species, including those with epidemiological relevance, can be used to analyze the vector's ecology and its association with transmission risk, and plan integrated regional vector surveillance and control programs. In this study, we model the environmental requirements of the principal North and Central American phlebotomine species and analyze three niche characteristics over future climate change scenarios: i) potential change in niche breadth, ii) direction and magnitude of niche centroid shifts, iii) shifts in elevation range. Niche identity between confirmed or incriminated Leishmania vector sand flies in Mexico, and human cases were analyzed. Niche models were constructed using sand fly occurrence datapoints from Canada, USA, Mexico, Guatemala and Belize. Nine non-correlated bioclimatic and four topographic data layers were used as niche components using GARP in OpenModeller. Both B2 and A2 climate change scenarios were used with two general circulation models for each scenario (CSIRO and HadCM3), for 2020, 2050 and 2080. There was an increase in niche breadth to 2080 in both scenarios for all species with the exception of Lutzomyia vexator. The principal direction of niche centroid displacement was to the northwest (64%), while the elevation range decreased greatest for tropical, and least for broad-range species. Lutzomyia cruciata is the only epidemiologically important species with high niche identity with that of Leishmania spp. in Mexico. Continued landscape modification in future climate change will provide an increased opportunity for the geographic expansion of NCA sand flys' ENM and human exposure to vectors of Leishmaniases.

  13. Current and future niche of North and Central American sand flies (Diptera: psychodidae in climate change scenarios.

    Directory of Open Access Journals (Sweden)

    David Moo-Llanes

    Full Text Available Ecological niche models are useful tools to infer potential spatial and temporal distributions in vector species and to measure epidemiological risk for infectious diseases such as the Leishmaniases. The ecological niche of 28 North and Central American sand fly species, including those with epidemiological relevance, can be used to analyze the vector's ecology and its association with transmission risk, and plan integrated regional vector surveillance and control programs. In this study, we model the environmental requirements of the principal North and Central American phlebotomine species and analyze three niche characteristics over future climate change scenarios: i potential change in niche breadth, ii direction and magnitude of niche centroid shifts, iii shifts in elevation range. Niche identity between confirmed or incriminated Leishmania vector sand flies in Mexico, and human cases were analyzed. Niche models were constructed using sand fly occurrence datapoints from Canada, USA, Mexico, Guatemala and Belize. Nine non-correlated bioclimatic and four topographic data layers were used as niche components using GARP in OpenModeller. Both B2 and A2 climate change scenarios were used with two general circulation models for each scenario (CSIRO and HadCM3, for 2020, 2050 and 2080. There was an increase in niche breadth to 2080 in both scenarios for all species with the exception of Lutzomyia vexator. The principal direction of niche centroid displacement was to the northwest (64%, while the elevation range decreased greatest for tropical, and least for broad-range species. Lutzomyia cruciata is the only epidemiologically important species with high niche identity with that of Leishmania spp. in Mexico. Continued landscape modification in future climate change will provide an increased opportunity for the geographic expansion of NCA sand flys' ENM and human exposure to vectors of Leishmaniases.

  14. Current and Future Niche of North and Central American Sand Flies (Diptera: Psychodidae) in Climate Change Scenarios

    Science.gov (United States)

    Moo-Llanes, David; Ibarra-Cerdeña, Carlos N.; Rebollar-Téllez, Eduardo A.; Ibáñez-Bernal, Sergio; González, Camila; Ramsey, Janine M.

    2013-01-01

    Ecological niche models are useful tools to infer potential spatial and temporal distributions in vector species and to measure epidemiological risk for infectious diseases such as the Leishmaniases. The ecological niche of 28 North and Central American sand fly species, including those with epidemiological relevance, can be used to analyze the vector's ecology and its association with transmission risk, and plan integrated regional vector surveillance and control programs. In this study, we model the environmental requirements of the principal North and Central American phlebotomine species and analyze three niche characteristics over future climate change scenarios: i) potential change in niche breadth, ii) direction and magnitude of niche centroid shifts, iii) shifts in elevation range. Niche identity between confirmed or incriminated Leishmania vector sand flies in Mexico, and human cases were analyzed. Niche models were constructed using sand fly occurrence datapoints from Canada, USA, Mexico, Guatemala and Belize. Nine non-correlated bioclimatic and four topographic data layers were used as niche components using GARP in OpenModeller. Both B2 and A2 climate change scenarios were used with two general circulation models for each scenario (CSIRO and HadCM3), for 2020, 2050 and 2080. There was an increase in niche breadth to 2080 in both scenarios for all species with the exception of Lutzomyia vexator. The principal direction of niche centroid displacement was to the northwest (64%), while the elevation range decreased greatest for tropical, and least for broad-range species. Lutzomyia cruciata is the only epidemiologically important species with high niche identity with that of Leishmania spp. in Mexico. Continued landscape modification in future climate change will provide an increased opportunity for the geographic expansion of NCA sand flys' ENM and human exposure to vectors of Leishmaniases. PMID:24069478

  15. Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

    Science.gov (United States)

    Luarte, Alejandro; Bátiz, Luis Federico; Wyneken, Ursula; Lafourcade, Carlos

    2016-01-01

    Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future. PMID:27195011

  16. Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

    Directory of Open Access Journals (Sweden)

    Alejandro Luarte

    2016-01-01

    Full Text Available Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

  17. CD271+ Mesenchymal Stem Cells as a Possible Infectious Niche for Leishmania infantum

    Science.gov (United States)

    Lopes, Carolina S.; Daifalla, Nada; Das, Bikul; Dias da Silva, Valdo; Campos-Neto, Antonio

    2016-01-01

    Visceral leishmaniasis (VL) is a serious and fatal disease. Therapeutic drugs are toxic and non-sterilizing. The etiological agents Leishmania infantum and Leishmania donovani cause active and asymptomatic diseases. Effective drugs to treat VL exist but unfortunately, post-treatment relapses are common. Little is known why drugs are non-sterilizing or how these intracellular pathogens can escape treatment. Here, using a murine model of VL we found that CD271+/Sca1+ bone marrow mesenchymal stem cells (BM-MSCs) are readily infected in vitro and in vivo by L. infantum. Because BM-MSCs express potent drug efflux pumps, e.g., ABCG2 it is possible that this unique intracellular infectious niche could allow L. infantum to escape anti-parasite drugs. PMID:27622907

  18. IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation.

    Science.gov (United States)

    Caselli, Anna; Olson, Timothy S; Otsuru, Satoru; Chen, Xiaohua; Hofmann, Ted J; Nah, Hyun-Duck; Grisendi, Giulia; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M

    2013-10-01

    The efficiency of hematopoietic stem cell (HSC) engraftment after bone marrow (BM) transplantation depends largely on the capacity of the marrow microenvironment to accept the transplanted cells. While radioablation of BM damages osteoblastic stem cell niches, little is known about their restoration and mechanisms governing their receptivity to engraft transplanted HSCs. We previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation. Here, we show that this reorganization represents proliferation of mature endosteal osteoblasts which seem to arise from a small subset of high-proliferative, relatively radio-resistant endosteal cells. Multiple layers of osteoblasts form along the endosteal surface within 48 hours after total body irradiation, concomitant with a peak in marrow cytokine expression. This niche reorganization fosters homing of the transplanted hematopoietic cells to the host marrow space and engraftment of long-term-HSC. Inhibition of insulin-like growth factor (IGF)-1-receptor tyrosine kinase signaling abrogates endosteal osteoblast proliferation and donor HSC engraftment, suggesting that the cytokine IGF-1 is a crucial mediator of endosteal niche reorganization and consequently donor HSC engraftment. Further understanding of this novel mechanism of IGF-1-dependent osteoblastic niche expansion and HSC engraftment may yield clinical applications for improving engraftment efficiency after clinical HSC transplantation.

  19. Cholinergic Enhancement of Cell Proliferation in the Postnatal Neurogenic Niche of the Mammalian Spinal Cord.

    Science.gov (United States)

    Corns, Laura F; Atkinson, Lucy; Daniel, Jill; Edwards, Ian J; New, Lauryn; Deuchars, Jim; Deuchars, Susan A

    2015-09-01

    The region surrounding the central canal (CC) of the spinal cord is a highly plastic area, defined as a postnatal neurogenic niche. Within this region are ependymal cells that can proliferate and differentiate to form new astrocytes and oligodendrocytes following injury and cerebrospinal fluid contacting cells (CSFcCs). The specific environmental conditions, including the modulation by neurotransmitters that influence these cells and their ability to proliferate, are unknown. Here, we show that acetylcholine promotes the proliferation of ependymal cells in mice under both in vitro and in vivo conditions. Using whole cell patch clamp in acute spinal cord slices, acetylcholine directly depolarized ependymal cells and CSFcCs. Antagonism by specific nicotinic acetylcholine receptor (nAChR) antagonists or potentiation by the α7 containing nAChR (α7*nAChR) modulator PNU 120596 revealed that both α7*nAChRs and non-α7*nAChRs mediated the cholinergic responses. Using the nucleoside analogue EdU (5-ethynyl-2'-deoxyuridine) as a marker of cell proliferation, application of α7*nAChR modulators in spinal cord cultures or in vivo induced proliferation in the CC region, producing Sox-2 expressing ependymal cells. Proliferation also increased in the white and grey matter. PNU 120596 administration also increased the proportion of cells coexpressing oligodendrocyte markers. Thus, variation in the availability of acetylcholine can modulate the rate of proliferation of cells in the ependymal cell layer and white and grey matter through α7*nAChRs. This study highlights the need for further investigation into how neurotransmitters regulate the response of the spinal cord to injury or during aging.

  20. GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord.

    Science.gov (United States)

    Corns, Laura F; Deuchars, Jim; Deuchars, Susan A

    2013-10-11

    The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the local environment, including neurotransmitters, is capable of affecting them. The neurotransmitter GABA is present around the central canal and is known to affect cells within other postnatal neurogenic niches. This study used whole cell patch clamp electrophysiology and intracellular dye-loading in in vitro Wistar rat spinal cord slices to characterise ependymal cells and their ability to respond to GABA. Ependymal cells were defined by their passive response properties and low input resistances. Extensive dye-coupling was observed between ependymal cells; this was confirmed as gap junction coupling using the gap junction blocker, 18β-glycyrrhetinic acid, which significantly increased the input resistance of ependymal cells. GABA depolarised all ependymal cells tested; the partial antagonism of this response by bicuculline and gabazine indicates that GABA(A) receptors contribute to this response. A lack of effect by baclofen suggests that GABA(B) receptors do not contribute to the GABAergic response. The ability of ependymal cells to respond to GABA suggests that GABA could be capable of influencing the proliferation and differentiation of cells within the neurogenic niche of the postnatal spinal cord.

  1. Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles

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    Amélie Rezza

    2016-03-01

    Full Text Available The hair follicle (HF is a complex miniorgan that serves as an ideal model system to study stem cell (SC interactions with the niche during growth and regeneration. Dermal papilla (DP cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplifying cell (TAC progenitors that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing, we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs, and the DP niche express a plethora of ligands and receptors. Signaling interaction network analysis reveals a bird’s-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach, this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth.

  2. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo.

    Science.gov (United States)

    Fleming, Heather E; Janzen, Viktor; Lo Celso, Cristina; Guo, Jun; Leahy, Kathleen M; Kronenberg, Henry M; Scadden, David T

    2008-03-06

    Wingless (Wnt) is a potent morphogen demonstrated in multiple cell lineages to promote the expansion and maintenance of stem and progenitor cell populations. Wnt effects are highly context dependent, and varying effects of Wnt signaling on hematopoietic stem cells (HSCs) have been reported. We explored the impact of Wnt signaling in vivo, specifically in the context of the HSC niche by using an osteoblast-specific promoter driving expression of the paninhibitor of canonical Wnt signaling, Dickkopf1 (Dkk1). Here we report that Wnt signaling was markedly inhibited in HSCs and, unexpectedly given prior reports, reduction in HSC Wnt signaling resulted in reduced p21Cip1 expression, increased cell cycling, and a progressive decline in regenerative function after transplantation. This effect was microenvironment determined, but irreversible if the cells were transferred to a normal host. Wnt pathway activation in the niche is required to limit HSC proliferation and preserve the reconstituting function of endogenous hematopoietic stem cells.

  3. Dystroglycan Suppresses Notch to Regulate Stem Cell Niche Structure and Function in the Developing Postnatal Subventricular Zone.

    Science.gov (United States)

    McClenahan, Freyja K; Sharma, Himanshu; Shan, Xiwei; Eyermann, Christopher; Colognato, Holly

    2016-09-12

    While the extracellular matrix (ECM) is known to regulate neural stem cell quiescence in the adult subventricular zone (SVZ), the function of ECM in the developing SVZ remains unknown. Here, we report that the ECM receptor dystroglycan regulates a unique developmental restructuring of ECM in the early postnatal SVZ. Dystroglycan is furthermore required for ependymal cell differentiation and assembly of niche pinwheel structures, at least in part by suppressing Notch activation in radial glial cells, which leads to the increased expression of MCI, Myb, and FoxJ1, transcriptional regulators necessary for acquisition of the multiciliated phenotype. Dystroglycan also regulates perinatal radial glial cell proliferation and transition into intermediate gliogenic progenitors, such that either acute or constitutive loss of function in dystroglycan results in increased oligodendrogenesis. These findings reveal a role for dystroglycan in orchestrating both the assembly and function of the SVZ neural stem cell niche.

  4. Single-cell and coupled GRN models of cell patterning in the Arabidopsis thaliana root stem cell niche

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    Alvarez-Buylla Elena R

    2010-10-01

    Full Text Available Abstract Background Recent experimental work has uncovered some of the genetic components required to maintain the Arabidopsis thaliana root stem cell niche (SCN and its structure. Two main pathways are involved. One pathway depends on the genes SHORTROOT and SCARECROW and the other depends on the PLETHORA genes, which have been proposed to constitute the auxin readouts. Recent evidence suggests that a regulatory circuit, composed of WOX5 and CLE40, also contributes to the SCN maintenance. Yet, we still do not understand how the niche is dynamically maintained and patterned or if the uncovered molecular components are sufficient to recover the observed gene expression configurations that characterize the cell types within the root SCN. Mathematical and computational tools have proven useful in understanding the dynamics of cell differentiation. Hence, to further explore root SCN patterning, we integrated available experimental data into dynamic Gene Regulatory Network (GRN models and addressed if these are sufficient to attain observed gene expression configurations in the root SCN in a robust and autonomous manner. Results We found that an SCN GRN model based only on experimental data did not reproduce the configurations observed within the root SCN. We developed several alternative GRN models that recover these expected stable gene configurations. Such models incorporate a few additional components and interactions in addition to those that have been uncovered. The recovered configurations are stable to perturbations, and the models are able to recover the observed gene expression profiles of almost all the mutants described so far. However, the robustness of the postulated GRNs is not as high as that of other previously studied networks. Conclusions These models are the first published approximations for a dynamic mechanism of the A. thaliana root SCN cellular pattering. Our model is useful to formally show that the data now available are not

  5. A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells

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    Fanny Ehret

    2015-11-01

    Full Text Available The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell–cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membrane for both adherent monolayers and neurospheres to address the potential influence of different niche cell types in the neurogenic zone of the adult hippocampus of mice. Astrocytes and endothelial cells enhanced precursor cell proliferation and neurosphere formation. Endothelial factors also led to a prolonged increase in proliferation after growth factor withdrawal, which otherwise induces differentiation. All niche cell types enhanced cell survival in monolayer cultures, endothelial cells also stimulated neuronal differentiation. A parallel trend elicited by astrocytes did not reach conventional statistical significance. Pericytes had variable effects here. We did not observe changes in differentiation in neurosphere co-cultures. In summary, our data indicate that in precursor cell culture protocols survival could be improved by adding as yet unknown factors physiologically contributed by astrocytes and endothelial cells. Our findings also underscore the complexity of the niche and the differential impact of factors from the different sources on distinct aspects of neuronal development. With the help of the models presented here, identification of these factors and their specific biological activity can now be initiated.

  6. GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord ☆

    OpenAIRE

    Corns, Laura F; Deuchars, Jim; Deuchars, Susan A

    2013-01-01

    The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the local environment, including neurotransmitters, is capable of affecting them. The neurotransmitter GABA is present around the central canal and is ...

  7. A systems biology approach for defining the molecular framework of the hematopoietic stem cell niche.

    Science.gov (United States)

    Charbord, Pierre; Pouget, Claire; Binder, Hans; Dumont, Florent; Stik, Grégoire; Levy, Pacifique; Allain, Fabrice; Marchal, Céline; Richter, Jenna; Uzan, Benjamin; Pflumio, Françoise; Letourneur, Franck; Wirth, Henry; Dzierzak, Elaine; Traver, David; Jaffredo, Thierry; Durand, Charles

    2014-09-04

    Despite progress in identifying the cellular composition of hematopoietic stem/progenitor cell (HSPC) niches, little is known about the molecular requirements of HSPC support. To address this issue, we used a panel of six recognized HSPC-supportive stromal lines and less-supportive counterparts originating from embryonic and adult hematopoietic sites. Through comprehensive transcriptomic meta-analyses, we identified 481 mRNAs and 17 microRNAs organized in a modular network implicated in paracrine signaling. Further inclusion of 18 additional cell strains demonstrated that this mRNA subset was predictive of HSPC support. Our gene set contains most known HSPC regulators as well as a number of unexpected ones, such as Pax9 and Ccdc80, as validated by functional studies in zebrafish embryos. In sum, our approach has identified the core molecular network required for HSPC support. These cues, along with a searchable web resource, will inform ongoing efforts to instruct HSPC ex vivo amplification and formation from pluripotent precursors.

  8. FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Ruri; Minami, Kaori; Tanaka, Satowa [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Nagai, Mami [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Matsui, Keiji; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Asano, Shigetaka [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan)

    2013-10-11

    Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.

  9. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche

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    LM McNamara

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs within their native environment of the stem cell niche in bone receive biochemical stimuli from surrounding cells. These stimuli likely influence how MSCs differentiate to become bone precursors. The ability of MSCs to undergo osteogenic differentiation is well established in vitro;however, the role of the natural cues from bone’s regulatory cells, osteocytes and osteoblasts in regulating the osteogenic differentiation of MSCs in vivo are unclear. In this study we delineate the role of biochemical signalling from osteocytes and osteoblasts, using conditioned media and co-culture experiments, to understand how they direct osteogenic differentiation of MSCs. Furthermore, the synergistic relationship between osteocytes and osteoblasts is examined by transwell co-culturing of MSCs with both simultaneously. Osteogenic differentiation of MSCs was quantified by monitoring alkaline phosphatase (ALP activity, calcium deposition and cell number. Intracellular ALP was found to peak earlier and there was greater calcium deposition when MSCs were co-cultured with osteocytes rather than osteoblasts, suggesting that osteocytes are more influential than osteoblasts in stimulating osteogenesis in MSCs. Osteoblasts initially stimulated an increase in the number of MSCs, but ultimately regulated MSC differentiation down the same pathway. Our novel co-culture system confirmed a synergistic relationship between osteocytes and osteoblasts in producing biochemical signals to stimulate the osteogenic differentiation of MSCs. This study provides important insights into the mechanisms at work within the native stem cell niche to stimulate osteogenic differentiation and outlines a possible role for the use of co-culture or conditioned media methodologies for tissue engineering applications.

  10. beta1 integrin maintains integrity of the embryonic neocortical stem cell niche.

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    Karine Loulier

    2009-08-01

    Full Text Available During embryogenesis, the neural stem cells (NSC of the developing cerebral cortex are located in the ventricular zone (VZ lining the cerebral ventricles. They exhibit apical and basal processes that contact the ventricular surface and the pial basement membrane, respectively. This unique architecture is important for VZ physical integrity and fate determination of NSC daughter cells. In addition, the shorter apical process is critical for interkinetic nuclear migration (INM, which enables VZ cell mitoses at the ventricular surface. Despite their importance, the mechanisms required for NSC adhesion to the ventricle are poorly understood. We have shown previously that one class of candidate adhesion molecules, laminins, are present in the ventricular region and that their integrin receptors are expressed by NSC. However, prior studies only demonstrate a role for their interaction in the attachment of the basal process to the overlying pial basement membrane. Here we use antibody-blocking and genetic experiments to reveal an additional and novel requirement for laminin/integrin interactions in apical process adhesion and NSC regulation. Transient abrogation of integrin binding and signalling using blocking antibodies to specifically target the ventricular region in utero results in abnormal INM and alterations in the orientation of NSC divisions. We found that these defects were also observed in laminin alpha2 deficient mice. More detailed analyses using a multidisciplinary approach to analyse stem cell behaviour by expression of fluorescent transgenes and multiphoton time-lapse imaging revealed that the transient embryonic disruption of laminin/integrin signalling at the VZ surface resulted in apical process detachment from the ventricular surface, dystrophic radial glia fibers, and substantial layering defects in the postnatal neocortex. Collectively, these data reveal novel roles for the laminin/integrin interaction in anchoring embryonic NSCs

  11. Imposed currents in galvanic cells

    OpenAIRE

    Biesheuvel, P.M.; Soestbergen, M.; Bazant, M. Z.

    2009-01-01

    We analyze the steady-state behavior of a general mathematical model for reversible galvanic cells, such as redox flow cells, reversible solid oxide fuel cells, and rechargeable batteries. We consider not only operation in the galvanic discharging mode, spontaneously generating a positive current against an external load, but also operation in two modes which require a net input of electrical energy: (i) the electrolytic charging mode, where a negative current is imposed to generate a voltage...

  12. Imposed currents in galvanic cells

    NARCIS (Netherlands)

    Biesheuvel, P.M.; Soestbergen, M.; Bazant, M.Z.

    2009-01-01

    We analyze the steady-state behavior of a general mathematical model for reversible galvanic cells, such as redox flow cells, reversible solid oxide fuel cells, and rechargeable batteries. We consider not only operation in the galvanic discharging mode, spontaneously generating a positive current ag

  13. Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for Neural Stem Cells.

    Science.gov (United States)

    Karumbaiah, Lohitash; Enam, Syed Faaiz; Brown, Ashley C; Saxena, Tarun; Betancur, Martha I; Barker, Thomas H; Bellamkonda, Ravi V

    2015-12-16

    Neural stem cells (NSCs) possess great potential for neural tissue repair after traumatic injuries to the central nervous system (CNS). However, poor survival and self-renewal of NSCs after injury severely limits its therapeutic potential. Sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs) linked to CS proteoglycans (CSPGs) in the brain extracellular matrix (ECM) have the ability to bind and potentiate trophic factor efficacy, and promote NSC self-renewal in vivo. In this study, we investigated the potential of CS-GAG hydrogels composed of monosulfated CS-4 (CS-A), CS-6 (CS-C), and disulfated CS-4,6 (CS-E) CS-GAGs as NSC carriers, and their ability to create endogenous niches by enriching specific trophic factors to support NSC self-renewal. We demonstrate that CS-GAG hydrogel scaffolds showed minimal swelling and degradation over a period of 15 days in vitro, absorbing only 6.5 ± 0.019% of their initial weight, and showing no significant loss of mass during this period. Trophic factors FGF-2, BDNF, and IL10 bound with high affinity to CS-GAGs, and were significantly (p hydrogels when compared to unsulfated hyaluronic acid (HA) hydrogels. Dissociated rat subventricular zone (SVZ) NSCs when encapsulated in CS-GAG hydrogels demonstrated ∼88.5 ± 6.1% cell viability in vitro. Finally, rat neurospheres in CS-GAG hydrogels conditioned with the mitogen FGF-2 demonstrated significantly (p hydrogels. Taken together, these findings demonstrate the ability of CS-GAG based hydrogels to regulate NSC self-renewal, and facilitate growth factor enrichment locally.

  14. Stromal-cell and cancer-cell exosomes leading the metastatic exodus for the promised niche

    OpenAIRE

    2013-01-01

    Exosomes are thought to play an important role in metastasis. Luga and colleagues have described the production of exosomes by stromal cells such as cancer-associated fibroblasts that are taken up by breast cancer cells and are then loaded with Wnt 11, which is associated with stimulation of the invasiveness and metastasis of the breast cancer cells. Previous studies have shown that exosomes produced by breast cancer cells are taken up by stromal fibroblasts and other stromal cells, suggestin...

  15. Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells.

    Science.gov (United States)

    Chiovaro, Francesca; Martina, Enrico; Bottos, Alessia; Scherberich, Arnaud; Hynes, Nancy E; Chiquet-Ehrismann, Ruth

    2015-10-15

    Tenascin-W is a matricellular protein with a dynamically changing expression pattern in development and disease. In adults, tenascin-W is mostly restricted to stem cell niches, and is also expressed in the stroma of solid cancers. Here, we analyzed its expression in the bone microenvironment of breast cancer metastasis. Osteoblasts were isolated from tumor-free or tumor-bearing bones of mice injected with MDA-MB231-1833 breast cancer cells. We found a fourfold upregulation of tenascin-W in the osteoblast population of tumor-bearing mice compared to healthy mice, indicating that tenascin-W is supplied by the bone metastatic niche. Transwell and co-culture studies showed that human bone marrow stromal cells (BMSCs) express tenascin-W protein after exposure to factors secreted by MDA-MB231-1833 breast cancer cells. To study tenascin-W gene regulation, we identified and analyzed the tenascin-W promoter as well as three evolutionary conserved regions in the first intron. 5'RACE analysis of mRNA from human breast cancer, glioblastoma and bone tissue showed a single tenascin-W transcript with a transcription start site at a noncoding first exon followed by exon 2 containing the ATG translation start. Site-directed mutagenesis of a SMAD4-binding element in proximity of the TATA box strongly impaired promoter activity. TGFβ1 induced tenascin-W expression in human BMSCs through activation of the TGFβ1 receptor ALK5, while glucocorticoids were inhibitory. Our experiments show that tenascin-W acts as a niche component for breast cancer metastasis to bone by supporting cell migration and cell proliferation of the cancer cells.

  16. Molecular Targets of Chromatin Repressive Mark H3K9me3 in Primate Progenitor Cells within Adult Neurogenic Niches

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    Michael R Foret

    2014-07-01

    Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

  17. Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

    Science.gov (United States)

    Willis, Lisa; Refahi, Yassin; Wightman, Raymond; Landrein, Benoit; Teles, José; Huang, Kerwyn Casey; Meyerowitz, Elliot M.

    2016-01-01

    Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3–4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell–cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control. PMID:27930326

  18. Pluripotent Stem Cells to Rebuild a Kidney: The Lymph Node as a Possible Developmental Niche.

    Science.gov (United States)

    Francipane, Maria Giovanna; Lagasse, Eric

    2016-01-01

    Kidney disease poses a global challenge. Stem cell therapy may offer an alternative therapeutic approach to kidney transplantation, which is often hampered by the limited supply of donor organs. While specific surface antigen markers have yet to be identified for the analysis and purification of kidney stem/progenitor cells for research or clinical use, the reprogramming of somatic cells to pluripotent cells and their differentiation into the various kidney lineages might represent a valuable strategy to create a renewable cell source for regenerative purposes. In this review, we first provide an overview of kidney development and explore current knowledge about the role of extra- and intrarenal cells in kidney repair and organogenesis. We then discuss recent advances in the 1) differentiation of rodent and human embryonic stem cells (ESCs) into renal lineages; 2) generation of induced pluripotent stem cells (iPSCs) from renal or nonrenal (kidney patient-derived) adult cells; 3) differentiation of iPSCs into renal lineages; and 4) direct transcriptional reprogramming of adult renal cells into kidney progenitor cells. Finally, we describe the lymph node as a potential three-dimensional (3D) in vivo environment for kidney organogenesis from pluripotent stem cells.

  19. Investigating the interaction between hematopoietic stem cells and their niche during embryonic development: optimizing the isolation of fetal and newborn stem cells from liver, spleen, and bone marrow.

    Science.gov (United States)

    Cao, Huimin; Williams, Brenda; Nilsson, Susan K

    2014-01-01

    Hematopoietic stem cells (HSCs) are maintained in a particular microenvironment termed a "niche." Within the niche, a number of critical molecules and supportive cell types have been identified to play key roles in modulating adult HSC quiescence, proliferation, differentiation, and reconstitution. However, unlike in the adult bone marrow (BM), the components of stem cell niches, as well as their interactions with fetal HSC during different stages of embryonic development, are poorly understood. During embryogenesis, hematopoietic development migrates through multiple organs, each with different cellular and molecular components and hence each with a potentially unique HSC niche. As a consequence, isolating fetal HSC from each organ at the time of hematopoietic colonization is fundamental for assessing and understanding both HSC function and their interactions with specific microenvironments. Herein, we describe methodologies for harvesting cells as well as the purification of stem and progenitors from fetal and newborn liver, spleen, and BM at various developmental stages following the expansion of hematopoiesis in the fetal liver at E14.5.

  20. Cholangiocarcinomas: New Insights from the Discovery of Stem Cell Niches in Peribiliary Glands of the Biliary Tree

    Directory of Open Access Journals (Sweden)

    Vincenzo Cardinale

    2014-01-01

    Full Text Available Peribiliary glands (PBGs are located in the large intrahepatic and extrahepatic bile ducts. Although they were described many years ago, their functions have been elucidated only in the last couple of years when our group demonstrated that PBGs are niches of multipotent stem/progenitor cells of endodermal origin. These cells express genes of multipotency and can be rapidly differentiated in vitro into hepatocytes, cholangiocytes, and endocrine pancreatic cells. PBGs share common features, in terms of stem/progenitor cell niches, with pancreatic duct glands and colon crypts, glandular structures representing in the adult life the endodermal remnants of fetal life. PBG stem/progenitor cells participate in the renewal of surface biliary epithelium and are active players in chronic pathologies of the biliary tree as well as in cholangiocarcinomas (CCA. Specifically, a large amount of recent evidence indicates that the pure mucin-CCA originates from PBGs; this could explain the similarities with pancreatic ductal adenocarcinoma and colorectal cancer, which also originate from transformed gland cells. In this paper, we summarized our recent findings concerning structure and functions of PBGs with the implications for liver pathophysiology and, specifically, for cancers of the biliary tree.

  1. Comparative Study on the Differentiation of Mesenchymal Stem Cells Between Fetal and Postnatal Rat Spinal Cord Niche.

    Science.gov (United States)

    Cao, Songying; Wei, Xiaowei; Li, Hui; Miao, Jianing; Zhao, Guifeng; Wu, Di; Liu, Bo; Zhang, Yi; Gu, Hui; Wang, Lili; Fan, Yang; An, Dong; Yuan, Zhengwei

    2016-01-01

    In a previous study, we established a prenatal surgical approach and transplanted mesenchymal stem cells (MSCs) into the fetal rat spinal column to treat neural tube defects (NTDs). We found that the transplanted MSCs survived and differentiated into neural lineage cells. Various cytokines and extracellular signaling systems in the spinal cord niche play an important role in cell differentiation. In this study, we observed the differentiation of transplanted MSCs in different spinal cord niches and further observed the expression of neurotrophic factors and growth factors in the spinal cord at different developmental stages to explore the mechanism of MSC differentiation in different spinal cord niches. The results showed that transplanted MSCs expressed markers of neural precursor cells (nestin), neurogliocytes (GFAP), and neurons (β-tubulin). The percentages of GFP(+)/nestin(+) double-positive cells in transplanted MSCs in E16, P1, and P21 rats were 18.31%, 12.18%, and 5.06%, respectively. The percentages of GFP(+)/GFAP(+) double-positive cells in E16, P1, and P21 rats were 32.01%, 15.35%, and 12.56%, respectively. The percentages of GFP(+)/β-tubulin(+) double-positive cells in E16, P1, and P21 were 11.76%, 7.62%, and 4.88%, respectively. The differentiation rates of MSCs in embryonic spinal cords were significantly higher than in postnatal spinal cords (p < 0.05). We found that the transplanted MSCs expressed synapsin-1 at different developmental stages. After MSC transplantation, we observed that neurotrophic factor-3 (NT-3), fibroblast growth factor-2 (FGF-2), FGF-8, transforming growth factor-α (TGF-α), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) significantly increased in the MSC transplantation group compared with the blank injection group. Furthermore, FGF-2 and VEGF expression were positively correlated with the number of surviving MSCs. In addition, we found that the expression of brain

  2. Bovine mammary stem cells: Transcriptome profiling and the stem cell niche

    Science.gov (United States)

    Identification and transcriptome analysis of mammary stem cells (MaSC) are important steps toward understanding the molecular basis of mammary epithelial growth, homeostasis and tissue repair. Our objective was to evaluate the molecular profiles of four categories of cells within the bovine mammary ...

  3. Endothelial cells create a stem cell niche in glioblastoma by providing NOTCH ligands that nurture self-renewal of cancer stem-like cells.

    Science.gov (United States)

    Zhu, Thant S; Costello, Mark A; Talsma, Caroline E; Flack, Callie G; Crowley, Jessica G; Hamm, Lisa L; He, Xiaobing; Hervey-Jumper, Shawn L; Heth, Jason A; Muraszko, Karin M; DiMeco, Francesco; Vescovi, Angelo L; Fan, Xing

    2011-09-15

    One important function of endothelial cells in glioblastoma multiforme (GBM) is to create a niche that helps promote self-renewal of cancer stem-like cells (CSLC). However, the underlying molecular mechanism for this endothelial function is not known. Since activation of NOTCH signaling has been found to be required for propagation of GBM CSLCs, we hypothesized that the GBM endothelium may provide the source of NOTCH ligands. Here, we report a corroboration of this concept with a demonstration that NOTCH ligands are expressed in endothelial cells adjacent to NESTIN and NOTCH receptor-positive cancer cells in primary GBMs. Coculturing human brain microvascular endothelial cells (hBMEC) or NOTCH ligand with GBM neurospheres promoted GBM cell growth and increased CSLC self-renewal. Notably, RNAi-mediated knockdown of NOTCH ligands in hBMECs abrogated their ability to induce CSLC self-renewal and GBM tumor growth, both in vitro and in vivo. Thus, our findings establish that NOTCH activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells and their surrounding endothelial cells in the tumor microenvironment, suggesting that targeting both CSLCs and their niche may provide a novel strategy to deplete CSLCs and improve GBM treatment.

  4. A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Sara N Gentry

    Full Text Available Hierarchical organized tissue structures, with stem cell driven cell differentiation, are critical to the homeostatic maintenance of most tissues, and this underlying cellular architecture is potentially a critical player in the development of a many cancers. Here, we develop a mathematical model of mutation acquisition to investigate how deregulation of the mechanisms preserving stem cell homeostasis contributes to tumor initiation. A novel feature of the model is the inclusion of both extrinsic and intrinsic chemical signaling and interaction with the niche to control stem cell self-renewal. We use the model to simulate the effects of a variety of types and sequences of mutations and then compare and contrast all mutation pathways in order to determine which ones generate cancer cells fastest. The model predicts that the sequence in which mutations occur significantly affects the pace of tumorigenesis. In addition, tumor composition varies for different mutation pathways, so that some sequences generate tumors that are dominated by cancerous cells with all possible mutations, while others are primarily comprised of cells that more closely resemble normal cells with only one or two mutations. We are also able to show that, under certain circumstances, healthy stem cells diminish due to the displacement by mutated cells that have a competitive advantage in the niche. Finally, in the event that all homeostatic regulation is lost, exponential growth of the cancer population occurs in addition to the depletion of normal cells. This model helps to advance our understanding of how mutation acquisition affects mechanisms that influence cell-fate decisions and leads to the initiation of cancers.

  5. Niche explosion.

    Science.gov (United States)

    Normark, Benjamin B; Johnson, Norman A

    2011-05-01

    The following syndrome of features occurs in several groups of phytophagous insects: (1) wingless females, (2) dispersal by larvae, (3) woody hosts, (4) extreme polyphagy, (5) high abundance, resulting in status as economic pests, (6) invasiveness, and (7) obligate parthenogenesis in some populations. If extreme polyphagy is defined as feeding on 20 or more families of hostplants, this syndrome is found convergently in several species of bagworm moths, tussock moths, root weevils, and 5 families of scale insects. We hypothesize that extreme polyphagy in these taxa results from "niche explosion", a positive feedback loop connecting large population size to broad host range. The niche explosion has a demographic component (sometimes called the "amplification effect" in studies of pathogens) as well as a population-genetic component, due mainly to the increased effectiveness of natural selection in larger populations. The frequent origins of parthenogenesis in extreme polyphages are, in our interpretation, a consequence of this increased effectiveness of natural selection and consequent reduced importance of sexuality. The niche explosion hypothesis makes detailed predictions about the comparative genomics and population genetics of extreme polyphages and related specialists. It has a number of potentially important implications, including an explanation for the lack of observed trade-offs between generalists and specialists, a re-interpretation of the ecological correlates of parthenogenesis, and a general expectation that Malthusian population explosions may be amplified by Darwinian effects.

  6. BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth.

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    Li, Jingyuan; Feng, Jifan; Liu, Yang; Ho, Thach-Vu; Grimes, Weston; Ho, Hoang Anh; Park, Shery; Wang, Songlin; Chai, Yang

    2015-04-20

    During embryogenesis, ectodermal stem cells adopt different fates and form diverse ectodermal organs, such as teeth, hair follicles, mammary glands, and salivary glands. Interestingly, these ectodermal organs differ in their tissue homeostasis, which leads to differential abilities for continuous growth postnatally. Mouse molars lose the ability to grow continuously, whereas incisors retain this ability. In this study, we found that a BMP-Smad4-SHH-Gli1 signaling network may provide a niche supporting transient Sox2+ dental epithelial stem cells in mouse molars. This mechanism also plays a role in continuously growing mouse incisors. The differential fate of epithelial stem cells in mouse molars and incisors is controlled by this BMP/SHH signaling network, which partially accounts for the different postnatal growth potential of molars and incisors. Collectively, our study highlights the importance of crosstalk between two signaling pathways, BMP and SHH, in regulating the fate of epithelial stem cells during organogenesis.

  7. Spatial analysis of plague in California: niche modeling predictions of the current distribution and potential response to climate change

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    Tucker James R

    2009-06-01

    Full Text Available Abstract Background Plague, caused by the bacterium Yersinia pestis, is a public and wildlife health concern in California and the western United States. This study explores the spatial characteristics of positive plague samples in California and tests Maxent, a machine-learning method that can be used to develop niche-based models from presence-only data, for mapping the potential distribution of plague foci. Maxent models were constructed using geocoded seroprevalence data from surveillance of California ground squirrels (Spermophilus beecheyi as case points and Worldclim bioclimatic data as predictor variables, and compared and validated using area under the receiver operating curve (AUC statistics. Additionally, model results were compared to locations of positive and negative coyote (Canis latrans samples, in order to determine the correlation between Maxent model predictions and areas of plague risk as determined via wild carnivore surveillance. Results Models of plague activity in California ground squirrels, based on recent climate conditions, accurately identified case locations (AUC of 0.913 to 0.948 and were significantly correlated with coyote samples. The final models were used to identify potential plague risk areas based on an ensemble of six future climate scenarios. These models suggest that by 2050, climate conditions may reduce plague risk in the southern parts of California and increase risk along the northern coast and Sierras. Conclusion Because different modeling approaches can yield substantially different results, care should be taken when interpreting future model predictions. Nonetheless, niche modeling can be a useful tool for exploring and mapping the potential response of plague activity to climate change. The final models in this study were used to identify potential plague risk areas based on an ensemble of six future climate scenarios, which can help public managers decide where to allocate surveillance resources

  8. A comparative pan-genome perspective of niche-adaptable cell-surface protein phenotypes in Lactobacillus rhamnosus.

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    Ravi Kant

    Full Text Available Lactobacillus rhamnosus is a ubiquitously adaptable Gram-positive bacterium and as a typical commensal can be recovered from various microbe-accessible bodily orifices and cavities. Then again, other isolates are food-borne, with some of these having been long associated with naturally fermented cheeses and yogurts. Additionally, because of perceived health benefits to humans and animals, numerous L. rhamnosus strains have been selected for use as so-called probiotics and are often taken in the form of dietary supplements and functional foods. At the genome level, it is anticipated that certain genetic variances will have provided the niche-related phenotypes that augment the flexible adaptiveness of this species, thus enabling its strains to grow and survive in their respective host environments. For this present study, we considered it functionally informative to examine and catalogue the genotype-phenotype variation existing at the cell surface between different L. rhamnosus strains, with the presumption that this might be relatable to habitat preferences and ecological adaptability. Here, we conducted a pan-genomic study involving 13 genomes from L. rhamnosus isolates with various origins. In using a benchmark strain (gut-adapted L. rhamnosus GG for our pan-genome comparison, we had focused our efforts on a detailed examination and description of gene products for certain functionally relevant surface-exposed proteins, each of which in effect might also play a part in niche adaptability among the other strains. Perhaps most significantly of the surface protein loci we had analyzed, it would appear that the spaCBA operon (known to encode SpaCBA-called pili having a mucoadhesive phenotype is a genomic rarity and an uncommon occurrence in L. rhamnosus. However, for any of the so-piliated L. rhamnosus strains, they will likely possess an increased niche-specific fitness, which functionally might presumably be manifested by a protracted transient

  9. Annexin 2 is a Regulator of SDF-1/CXCL12 Function in the Hematopoietic Stem Cell Endosteal Niche

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    Jung, Younghun; Shiozawa, Yusuke; Wang, Jingcheng; Patel, Lalit R; Havens, Aaron M.; Song, Junhui; Krebsbach, Paul H.; Roodman, G. David; Taichman, Russell S.

    2010-01-01

    Objectives Previously we reported that annexin 2 (anxa2) plays an important role in hematopoietic stem cell (HSC) localization to the endosteal/osteoblastic marrow niche. The study explored the role that annexin 2 plays in presenting stromal derived factor-1 (SDF-1 or CXCL12) to HSCs. Materials and Methods Competitive long-term bone marrow transplant (CLT-BMT) assays were used to determine if HSC engraftment is altered in annexin 2-deficient animals. Colony-forming cell assays, CXCL12 Elisa, and real-time RT-PCR analyses were employed to determine stem or progenitor cell mobilization by G-CSF. Immunohistochemistry, immunoprecipitation, binding assays, and chemotactic assays were employed to determine if annexin 2 is associated with CXCL12. Degradation assays were also used to determine if annexin 2 and CXCL12 protect each other from proteolytic degradation. Results Anxa2−/− animals have fewer HSC in their marrows, and the HSCs in anxa2−/− animals express less CXCR4 and CXCR7 suggesting a cell intrinsic defect. Transplantation studies of wild-type marrow into anxa2−/− animals demonstrated a cell extrinsic defect in the anxa2−/− animals. CXCL12 binds directly to annexin 2, and this interaction facilitates the presentation of CXCL12 to HSCs. Yet the binding of CXCL12 to annexin 2 does not protect CXCL12 from proteolytic cleavage following stem or progenitor cell mobilization by G-CSF. Conclusions These results suggest that annexin 2 serves as an anchor for CXCL12 to help in the localization of HSCs to the niche. PMID:21108988

  10. Exosomes as novel regulators of adult neurogenic niches

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    Luis Federico Batiz

    2016-01-01

    Full Text Available Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ of the dentate gyrus (DG in the hippocampus, and the sub-ventricular zone (SVZ of the lateral ventricles. SGZ newborn neurons are destined to the granular cell layer of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb. The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs, which reside in a unique and specialized microenvironment known as neurogenic niche. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs. EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs, proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult

  11. Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells.

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    Butler, Jason M; Gars, Eric J; James, Daylon J; Nolan, Daniel J; Scandura, Joseph M; Rafii, Shahin

    2012-08-09

    Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that coculture of CD34(+) hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45(+)CD34(+) progenitor cells, and 23-fold expansion of CD45(+) Lin(-)CD34(hi+)CD45RA(-)CD49f(+) stem and progenitor cells over a 12-day period. Compared with cytokines alone, coculture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders.

  12. Endocannabinoids are expressed in bone marrow stromal niches and play a role in interactions of hematopoietic stem and progenitor cells with the bone marrow microenvironment.

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    Jiang, Shuxian; Zagozdzon, Radoslaw; Jorda, Meritxell Alberich; Parmar, Kalindi; Fu, Yigong; Williams, John S; Wood, Jodi Anne T; Makriyannis, Alexandros; Banu, Naheed; Avraham, Shalom; Groopman, Jerome E; Avraham, Hava Karsenty

    2010-11-12

    Endocannabinoids are lipid signaling molecules that act via G-coupled receptors, CB(1) and CB(2). The endocannabinoid system is capable of activation of distinct signaling pathways on demand in response to pathogenic events or stimuli, hereby enhancing cell survival and promoting tissue repair. However, the role of endocannabinoids in hematopoietic stem and progenitor cells (HSPCs) and their interaction with hematopoietic stem cells (HSC) niches is not known. HSPCs are maintained in the quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signaling. We report that HSPCs express the CB(1) receptors and that BM stromal cells secrete endocannabinoids, anandamide (AEA) (35 pg/10(7) cells), and 2-AG (75.2 ng/10(7) cells). In response to the endotoxin lipopolysaccharide (LPS), elevated levels of AEA (75.6 pg/10(7) cells) and 2-AG (98.8 ng/10(7) cells) were secreted from BM stromal cells, resulting in migration and trafficking of HSPCs from the BM niches to the peripheral blood. Furthermore, administration of exogenous cannabinoid CB(1) agonists in vivo induced chemotaxis, migration, and mobilization of human and murine HSPCs. Cannabinoid receptor knock-out mice Cnr1(-/-) showed a decrease in side population (SP) cells, whereas fatty acid amide hydrolase (FAAH)(-/-) mice, which have elevated levels of AEA, yielded increased colony formation as compared with WT mice. In addition, G-CSF-induced mobilization in vivo was modulated by endocannabinoids and was inhibited by specific cannabinoid antagonists as well as impaired in cannabinoid receptor knock-out mice Cnr1(-/-), as compared with WT mice. Thus, we propose a novel function of the endocannabinoid system, as a regulator of HSPC interactions with their BM niches, where endocannabinoids are expressed in HSC niches and under stress conditions, endocannabinoid expression levels are enhanced to induce HSPC migration for proper hematopoiesis.

  13. Embryonic anti-aging niche.

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    Conboy, Irina M; Yousef, Hanadie; Conboy, Michael J

    2011-05-01

    Although functional organ stem cells persist in the old, tissue damage invariably overwhelms tissue repair, ultimately causing the demise of an organism. The poor performance of stem cells in an aged organ, such as skeletal muscle, is caused by the changes in regulatory pathways such as Notch, MAPK and TGF-β, where old differentiated tissue actually inhibits its own regeneration. This perspective analyzes the current literature on regulation of organ stem cells by their young versus old niches and suggests that determinants of healthy and prolonged life might be under a combinatorial control of cell cycle check point proteins and mitogens, which need to be tightly balanced in order to promote tissue regeneration without tumor formation. While responses of adult stem cells are regulated extrinsically and age-specifically, we put forward experimental evidence suggesting that embryonic cells have an intrinsic youthful barrier to aging and produce soluble pro-regenerative proteins that signal the MAPK pathway for rejuvenating myogenesis. Future identification of this activity will improve our understanding of embryonic versus adult regulation of tissue regeneration suggesting novel strategies for organ rejuvenation. Comprehensively, the current intersection of aging and stem cell science indicates that if the age-imposed decline in the regenerative capacity of stem cells was understood, the debilitating lack of organ maintenance in the old could be ameliorated and perhaps, even reversed.

  14. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the pre-metastatic niche

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    Erler, Janine T.; Bennewith, Kevin L.; Cox, Thomas R.; Lang, Georgina; Bird, Demelza; Koong, Albert; Le, Quynh-Thu; Giaccia, Amato J.

    2010-01-01

    Summary Tumor cell metastasis is facilitated by “pre-metastatic niches” formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for pre-metastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at pre-metastatic sites, cross-links collagen-IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to cross-linked collagen-IV and produce matrix metalloproteinase-2 which cleaves collagen, enhancing the invasion and recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents CD11b+ cell recruitment and metastatic growth. CD11b+ cells and LOX also co-localize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in pre-metastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease. PMID:19111879

  15. Cellular organization of the central canal ependymal zone, a niche of latent neural stem cells in the adult mammalian spinal cord.

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    Hamilton, L K; Truong, M K V; Bednarczyk, M R; Aumont, A; Fernandes, K J L

    2009-12-15

    A stem cell's microenvironment, or "niche," is a critical regulator of its behaviour. In the adult mammalian spinal cord, central canal ependymal cells possess latent neural stem cell properties, but the ependymal cell niche has not yet been described. Here, we identify important similarities and differences between the central canal ependymal zone and the forebrain subventricular zone (SVZ), a well-characterized niche of neural stem cells. First, direct immunohistochemical comparison of the spinal cord ependymal zone and the forebrain SVZ revealed distinct patterns of neural precursor marker expression. In particular, ependymal cells in the spinal cord were found to be bordered by a previously uncharacterized sub-ependymal layer, which is relatively less elaborate than that of the SVZ and comprised of small numbers of astrocytes, oligodendrocyte progenitors and neurons. Cell proliferation surrounding the central canal occurs in close association with blood vessels, but unlike in the SVZ, involves mainly ependymal rather than sub-ependymal cells. These proliferating ependymal cells typically self-renew rather than produce transit-amplifying progenitors, as they generate doublets of progeny that remain within the ependymal layer and show no evidence of a lineage relationship to sub-ependymal cells. Interestingly, the dorsal pole of the central canal was found to possess a sub-population of tanycyte-like cells that express markers of both ependymal cells and neural precursors, and their presence correlates with higher numbers of dorsally proliferating ependymal cells. Together, these data identify key features of the spinal cord ependymal cell niche, and suggest that dorsal ependymal cells possess the potential for stem cell activity. This work provides a foundation for future studies aimed at understanding ependymal cell regulation under normal and pathological conditions.

  16. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

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    Naoki Tajiri

    Full Text Available Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  17. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Science.gov (United States)

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  18. bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche

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    Lam, Victoria; Tokusumi, Tsuyoshi; Tokusumi, Yumiko; Schulz, Robert A., E-mail: rschulz@nd.edu

    2014-10-24

    Highlights: • bantam miRNA is endogenously expressed in the hematopoietic progenitor niche. • bantam is necessary and sufficient to induce cellular proliferation in the PSC. • bantam is upstream of the Insulin Receptor signaling pathway. • A model for positive regulation of hematopoietic niche growth is proposed. - Abstract: The Drosophila hematopoietic system is utilized in this study to gain novel insights into the process of growth control of the hematopoietic progenitor niche in blood development. The niche microenvironment is an essential component controlling the balance between progenitor populations and differentiated, mature blood cells and has been shown to lead to hematopoietic malignancies in humans when misregulated. MicroRNAs are one class of regulators associated with blood malignancies; however, there remains a relative paucity of information about the role of miRNAs in the niche. Here we demonstrate that bantam miRNA is endogenously active in the Drosophila hematopoietic progenitor niche, the posterior signaling center (PSC), and functions in the primary hematopoietic organ, the lymph gland, as a positive regulator of growth. Loss of bantam leads to a significant reduction in the PSC and overall lymph gland size, as well as a loss of the progenitor population and correlative premature differentiation of mature hemocytes. Interestingly, in addition to being essential for proper lymph gland development, we have determined bantam to be a novel upstream component of the insulin signaling cascade in the PSC and have unveiled dMyc as one factor central to bantam activity. These important findings identify bantam as a new hematopoietic regulator, place it in an evolutionarily conserved signaling pathway, present one way in which it is regulated, and provide a mechanism through which it facilitates cellular proliferation in the hematopoietic niche.

  19. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.

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    Shafiee, Abbas; Patel, Jatin; Wong, Ho Yi; Donovan, Prudence; Hutmacher, Dietmar W; Fisk, Nicholas M; Khosrotehrani, Kiarash

    2017-02-01

    The prospect of using endothelial progenitors is currently hampered by their low engraftment upon transplantation. We report that mesenchymal stem/stromal cells (MSCs), independent of source and age, improve the engraftment of endothelial colony forming cells (ECFCs). MSC coculture altered ECFC appearance to an elongated mesenchymal morphology with reduced proliferation. ECFC primed via MSC contact had reduced self-renewal potential, but improved capacity to form tube structures in vitro and engraftment in vivo Primed ECFCs displayed major differences in transcriptome compared to ECFCs never exposed to MSCs, affecting genes involved in the cell cycle, up-regulating of genes influencing mesenchymal transition, adhesion, extracellular matrix. Inhibition of NOTCH signaling, a potential upstream regulator of mesenchymal transition, in large part modulated this gene expression pattern and functionally reversed the mesenchymal morphology of ECFCs. The collective results showed that primed ECFCs survive better and undergo a mesenchymal transition that is dependent on NOTCH signaling, resulting in significantly increased vasculogenic potential.-Shafiee, A., Patel, J., Wong, H. Y., Donovan, P., Hutmacher, D. W., Fisk, N. M., Khosrotehrani, K. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.

  20. Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines

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    Maria Notara

    2015-11-01

    Full Text Available Ultraviolet light B (UVB-irradiation is linked to various ocular pathologies such as limbal stem cell defects in pterygium. Despite the large circumstantial evidence linking UVB irradiation and limbal epithelial stem cell damage, the precise molecular responses of limbal stem cells to UVB irradiation are unclear. Here the effect of UVB irradiation on the putative stem cell phenotype, limbal niche cells and the subsequent effects on corneal (lymphangiogenic privilege were investigated. Primary human limbal epithelial stem cells and fibroblasts were irradiated with 0.02 J/cm2 of UVB, a low dose corresponding to 3 min of solar irradiation. UVB irradiation caused significant reduction of limbal epithelial and limbal fibroblast proliferation for 24 h, but apoptosis of limbal epithelial stem cells only. Moreover, UVB induced stem-like character loss of limbal epithelial cells, as their colony forming efficiency and putative stem cell marker expression significantly decreased. Interestingly, limbal epithelial cells co-cultured with UVB-irradiated limbal fibroblasts also exhibited loss of stem cell character and decrease of colony forming efficiency. Conditioned media from limbal epithelial cells inhibited lymphatic endothelial cell proliferation and tube network complexity; however this effect diminished following UVB irradiation. In contrast, pro-inflammatory and macrophage-recruiting cytokines such as TNFα, IFNγ and MCP1 were significantly upregulated following cell irradiation of limbal fibroblasts. These data demonstrate the key role of the limbal stem cell niche in response to UVB and subsequent (lymphangiogenic and inflammatory events. These data suggest that the known pro(lymphangiogenic effect of UVB irradiation in pterygium is not linked to a direct up-regulation of pro-angiogenic cytokines, but rather to indirect macrophage-recruiting cytokines being upregulated after UVB irradiation.

  1. Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cell–collagen constructs: A three-dimensional in vitro model to study hematopoietic stem cell niche

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    WY Lai

    2013-10-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and osteoblasts are important niche cells for hematopoietic stem cells (HSCs in bone marrow osteoblastic niche. Here, we aim to partially reconstitute the bone marrow HSC niche in vitro using collagen microencapsulation for investigation of the interactions between HSCs and MSCs. Mouse MSCs (mMSCs microencapsulated in collagen were osteogenically differentiated to derive a bone-like matrix consisting of osteocalcin, osteopontin, and calcium deposits and secreted bone morphogenic protein 2 (BMP2. Decellularized bone-like matrix was seeded with fluorescence-labeled human MSCs and HSCs. Comparing with pure collagen scaffold, significantly more HSCs and HSC–MSC pairs per unit area were found in the decellularized bone-like matrix. Moreover, incubation with excess neutralizing antibody of BMP2 resulted in a significantly higher number of HSC per unit area than that without in the decellularized matrix. This work suggests that the osteogenic differentiated MSC–collagen microsphere is a valuable three-dimensional in vitro model to elucidate cell–cell and cell–matrix interactions in HSC niche.

  2. Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.

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    Wenting Zhang

    Full Text Available We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC using an osteoblast (OSB-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1 optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2 replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.

  3. Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery

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    Mao, Angelo S.; Shin, Jae-Won; Utech, Stefanie; Wang, Huanan; Uzun, Oktay; Li, Weiwei; Cooper, Madeline; Hu, Yuebi; Zhang, Liyuan; Weitz, David A.; Mooney, David J.

    2016-10-01

    Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel's mechanical properties. Here, we report a microfluidic-based method for encapsulating single cells in an approximately six-micrometre layer of alginate that increases the proportion of cell-containing microgels by a factor of ten, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that, for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.

  4. Niche-Independent Symmetrical Self-Renewal of a Mammalian Tissue Stem Cell

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    Gorba, Thorsten; Reitano, Erika; Toselli, Mauro; Biella, Gerardo; Sun, Yirui; Sanzone, Sveva; Ying, Qi-Long; Cattaneo, Elena

    2005-01-01

    Pluripotent mouse embryonic stem (ES) cells multiply in simple monoculture by symmetrical divisions. In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells has proven elusive. Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres. The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated. Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF) is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS) cells. NS cells were derived first from mouse ES cells. Neural lineage induction was followed by growth factor addition in basal culture media. In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic. After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain. Colonies generated from single NS cells all produce neurons upon growth factor withdrawal. NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia. Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain. Similar NS cells can be generated from human ES cells and human foetal brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells. The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying differentiation. These

  5. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell.

    Directory of Open Access Journals (Sweden)

    Luciano Conti

    2005-09-01

    Full Text Available Pluripotent mouse embryonic stem (ES cells multiply in simple monoculture by symmetrical divisions. In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells has proven elusive. Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres. The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated. Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2 and epidermal growth factor (EGF is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS cells. NS cells were derived first from mouse ES cells. Neural lineage induction was followed by growth factor addition in basal culture media. In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic. After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain. Colonies generated from single NS cells all produce neurons upon growth factor withdrawal. NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia. Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain. Similar NS cells can be generated from human ES cells and human foetal brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells. The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying

  6. Direct Measurements of Human Colon Crypt Stem Cell Niche Genetic Fidelity: The Role of Chance in Non-Darwinian Mutation Selection

    Directory of Open Access Journals (Sweden)

    Haeyoun eKang

    2013-10-01

    Full Text Available Perfect human stem cell genetic fidelity would prevent aging and cancer. However, perfection would be difficult to achieve, and aging is universal and cancers common. A hypothesis is that because mutations are inevitable over a human lifetime, downstream mechanisms have evolved to manage the deleterious effects of beneficial and lethal mutations. In the colon, a crypt stem cell architecture reduces the number of mitotic cells at risk for mutation accumulation, and multiple niche stem cells ensure that a lethal mutation within any single stem cell does not lead to crypt death. In addition, the architecture of the colon crypt stem cell niche may harness probability or chance to randomly discard many beneficial mutations that might lead to cancer. An analysis of somatic chromosome copy number alterations (CNAs reveals a lack of perfect fidelity in individual normal human crypts, with age-related increases and higher frequencies in ulcerative colitis, a proliferative, inflammatory disease. The age-related increase in somatic CNAs appears consistent with relatively normal replication error and cell division rates. Surprisingly, and similar to point mutations in cancer genomes, the types of crypt mutations were more consistent with random fixation rather than selection. In theory, a simple non-Darwinian way to nullify selection is to reduce the size of the reproducing population. Fates are more determined by chance rather than selection in very small populations, and therefore selection may be minimized within small crypt niches. The desired effect is that many beneficial mutations that might lead to cancer are randomly lost by drift rather than fixed by selection. The subdivision of the colon into multiple very small stem cell niches may trade Darwinian evolution for non-Darwinian somatic cell evolution, capitulating to aging but reducing cancer risks.

  7. Bong-Han Corpuscles as Possible Stem Cell Niches on the Organ-Surfaces

    Directory of Open Access Journals (Sweden)

    Min Su Kim

    2008-03-01

    Full Text Available Objectives : Showing that Bong-Han corpuscles(BHC are suppliers of the stem cells in adulthood, and the Bong-Han ducts(BHD are transportation routes of stem cells. Methods : BHC and BHD were obtained from the internal organ-surfaces of rats. The sliced BHC and BHD were immunostained with various stem cell markers. Extracellular matrices were also analyzed by immunohistochemistry. Result : The presence of mesenchymal stem cells was confirmed by the expression of Integrin beta 1, Collagen type 1 and Fibronectin. But CD54 was not expressed. The hematopoietic stem cell marker, Thy 1 was strongly expressed. BHDs showed Collagen type 1, Fibronectin, and vWF expression. Conclusion : Both hematopoietic and mesenchymal stem cell markers were expressed strongly in BHC similarly as in bone marrow. An endothelial cell marker(vWF demonstrated the possibility of the stem cell transportation routes of BHD.

  8. Neural activity control of neural stem cells and SVZ niche response to brain injury

    OpenAIRE

    Páez González, Patricia

    2014-01-01

    Patricia Paez-Gonzalez Kuo Lab, Dept. of Cell Biology, Duke University Medical Center, NC,USA. Date: 11/16/2014 Utilizing stem cells in the adult brain hold great promise for regenerative medicine. Harnessing ability of adult neural stem cells (NSCs) to generate new neurons or other types of brain cells may provide much needed therapies for patients suffering from brain injuries or neuro-degenerative diseases such as Parkinson’s, Scizophrenia, or Alzheimer’s disease. However...

  9. Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny

    NARCIS (Netherlands)

    Yin, Xiaolei; Farin, Henner F; van Es, Johan H; Clevers, Hans; Langer, Robert; Karp, Jeffrey M

    2014-01-01

    Although Lgr5(+) intestinal stem cells have been expanded in vitro as organoids, homogeneous culture of these cells has not been possible thus far. Here we show that two small molecules, CHIR99021 and valproic acid, synergistically maintain self-renewal of mouse Lgr5(+) intestinal stem cells, result

  10. Bone Marrow Stem Cells in Clinical Application: Harnessing Paracrine Roles and Niche Mechanisms

    Science.gov (United States)

    Backly, Rania M. El; Cancedda, Ranieri

    The being of any individual throughout life is a dynamic process relying on the capacity to retain processes of self-renewal and differentiation, both of which are hallmarks of stem cells. Although limited in the adult human organism, regeneration and repair do take place in virtue of the presence of adult stem cells. In the bone marrow, two major populations of stem cells govern the dynamic equilibrium of both hemopoiesis and skeletal homeostasis; the hematopoietic and the mesenchymal stem cells. Recent cell based clinical trials utilizing bone marrow-derived stem cells as therapeutic agents have revealed promising results, while others have failed to display as such. It is therefore imperative to strive to understand the mechanisms by which these cells function in vivo, how their properties can be maintained ex-vivo, and to explore further their recently highlighted immunomodulatory and trophic effects.

  11. Long-term B cell depletion in murine lupus eliminates autoantibody-secreting cells and is associated with alterations in the kidney plasma cell niche.

    Science.gov (United States)

    Wang, Wensheng; Rangel-Moreno, Javier; Owen, Teresa; Barnard, Jennifer; Nevarez, Sarah; Ichikawa, H Travis; Anolik, Jennifer H

    2014-04-01

    Autoantibodies to dsDNA, produced by autoreactive plasma cells (PCs), are a hallmark of systemic lupus erythematosus and play a key role in disease pathogenesis. Recent data suggest that autoreactive PCs accumulate not only in lymphoid tissues, but also in the inflamed kidney in lupus nephritis. We hypothesized that the variable efficacy of anti-CD20 (rituximab)-mediated B cell depletion in systemic lupus erythematosus may be related to the absence of an effect on autoreactive PCs in the kidney. In this article, we report that an enrichment of autoreactive dsDNA Ab-secreting cells (ASCs) in the kidney of lupus-prone mice (up to 40% of the ASCs) coincided with a progressive increase in splenic germinal centers and PCs, and an increase in renal expression for PC survival factors (BAFF, a proliferation-inducing ligand, and IL-6) and PC attracting chemokines (CXCL12). Short-term treatment with anti-CD20 (4 wk) neither decreased anti-dsDNA nor IgG ASCs in different anatomical locations. However, long-term treatment (12 wk) significantly reduced both IgG- and dsDNA-specific ASCs. In addition, long-term treatment substantially decreased splenic germinal center and PC generation, and unexpectedly reduced the expression for PC survival factors in the kidney. These results suggest that prolonged B cell depletion may alter the PC survival niche in the kidney, regulating the accumulation and maintenance of autoreactive PCs.

  12. The niche factor syndecan-1 regulates the maintenance and proliferation of neural progenitor cells during mammalian cortical development.

    Directory of Open Access Journals (Sweden)

    Qingjie Wang

    Full Text Available Neural progenitor cells (NPCs divide and differentiate in a precisely regulated manner over time to achieve the remarkable expansion and assembly of the layered mammalian cerebral cortex. Both intrinsic signaling pathways and environmental factors control the behavior of NPCs during cortical development. Heparan sulphate proteoglycans (HSPG are critical environmental regulators that help modulate and integrate environmental cues and downstream intracellular signals. Syndecan-1 (Sdc1, a major transmembrane HSPG, is highly enriched in the early neural germinal zone, but its function in modulating NPC behavior and cortical development has not been explored. In this study we investigate the expression pattern and function of Sdc1 in the developing mouse cerebral cortex. We found that Sdc1 is highly expressed by cortical NPCs. Knockdown of Sdc1 in vivo by in utero electroporation reduces NPC proliferation and causes their premature differentiation, corroborated in isolated cells in vitro. We found that Sdc1 knockdown leads to reduced levels of β-catenin, indicating reduced canonical Wnt signaling. Consistent with this, GSK3β inhibition helps rescue the Sdc1 knockdown phenotype, partially restoring NPC number and proliferation. Moreover, exogenous Wnt protein promotes cortical NPC proliferation, but this is prevented by Sdc1 knockdown. Thus, Sdc1 in the germinal niche is a key HSPG regulating the maintenance and proliferation of NPCs during cortical neurogenesis, in part by modulating the ability of NPCs to respond to Wnt ligands.

  13. JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

    Science.gov (United States)

    Mohammad, H; Marchisella, F; Ortega-Martinez, S; Hollos, P; Eerola, K; Komulainen, E; Kulesskaya, N; Freemantle, E; Fagerholm, V; Savontous, E; Rauvala, H; Peterson, B D; van Praag, H; Coffey, E T

    2016-11-15

    Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.203.

  14. Periodontal ligament stem cell niche and periodontal tissue regeneration%牙周膜干细胞巢与牙周组织再生

    Institute of Scientific and Technical Information of China (English)

    孙静

    2011-01-01

    牙周膜干细胞巢是牙周膜干细胞周围的微环境,由干细胞周围的支持细胞、黏附分子和基质组成,其在牙周组织的发育、牙周病的发生与发展以及牙周组织再生等方面具有重要的作用。本文将从影响巢结构稳定的因素及其在牙周组织再生中的作用等方面作一综述。%Periodontal ligament stem cell niche is the micro-environment surrounding of the periodontal stem cells, containing the supporting cells of stem cells, adhesion molecules and matrix composition. It is maybe more reasonable to make the periodontal stem cells and their niche to be a whole functional subject during physiologic and pathologic processes. We will review the factors that related to periodontal ligament stem cell niche especially in the process of periodontal tissue regeneration.

  15. Predicting the current potential and future world wide distribution of the onion maggot, Delia antiqua using maximum entropy ecological niche modeling

    Science.gov (United States)

    Feng, Jinian

    2017-01-01

    Climate change will markedly impact biology, population ecology, and spatial distribution patterns of insect pests because of the influence of future greenhouse effects on insect development and population dynamics. Onion maggot, Delia antiqua, larvae are subterranean pests with limited mobility, that directly feed on bulbs of Allium sp. and render them completely unmarketable. Modeling the spatial distribution of such a widespread and damaging pest is crucial not only to identify current potentially suitable climactic areas but also to predict where the pest is likely to spread in the future so that appropriate monitoring and management programs can be developed. In this study, Maximum Entropy Niche Modeling was used to estimate the current potential distribution of D. antiqua and to predict the future distribution of this species in 2030, 2050, 2070 and 2080 by using emission scenario (A2) with 7 climate variables. The results of this study show that currently highly suitable habitats for D.antiqua occur throughout most of East Asia, some regions of North America, Western Europe, and Western Asian countries near the Caspian sea and Black Sea. In the future, we predict an even broader distribution of this pest spread more extensively throughout Asia, North America and Europe, particularly in most of European countries, Central regions of United States and much of East Asia. Our present day and future predictions can enhance strategic planning of agricultural organizations by identifying regions that will need to develop Integrated Pest Management programs to manage the onion maggot. The distribution forecasts will also help governments to optimize economic investments in management programs for this pest by identifying regions that are or will become less suitable for current and future infestations. PMID:28158259

  16. Cancer Microenvironment: What Can We Learn from the Stem Cell Niche

    OpenAIRE

    2015-01-01

    Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle—also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also cont...

  17. Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrin αV.

    Directory of Open Access Journals (Sweden)

    Akiko Niibori-Nambu

    Full Text Available Glioma initiating cells (GICs are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanism of GIC maintenance/differentiation, we established GIC clones having the potential to differentiate into malignant gliomas, and subjected to DNA microarray/iTRAQ based integrated proteomics. 21,857 mRNAs and 8,471 proteins were identified and integrated into a gene/protein expression analysis chart. Gene Ontology analysis revealed that the expression of cell adhesion molecules, including integrin subfamilies, such as α2 and αV, and extracellular matrices (ECMs, such as collagen IV (COL4, laminin α2 (LAMA2, and fibronectin 1 (FN, was significantly upregulated during serum-induced GIC differentiation. This differentiation process, accompanied by the upregulation of MAPK as well as glioma specific proteins in GICs, was dramatically accelerated in these ECM (especially FN-coated dishes. Integrin αV blocking antibody and RGD peptide significantly suppressed early events in GIC differentiation, suggesting that the coupling of ECMs to integrin αV is necessary for GIC differentiation. In addition, the expression of integrin αV and its strong ligand FN was prominently increased in glioblastomas developed from mouse intracranial GIC xenografts. Interestingly, during the initial phase of GIC differentiation, the RGD treatment significantly inhibited GIC proliferation and raised their sensitivity against anti-cancer drug temozolomide (TMZ. We also found that combination treatments of TMZ and RGD inhibit glioma progression and lead the longer survival of mouse intracranial GIC xenograft model. These results indicate that GICs induce/secrete ECMs to develop microenvironments with serum factors, namely differentiation niches that further stimulate GIC differentiation and proliferation via the integrin recognition motif RGD. A combination of RGD treatment with TMZ could have the higher inhibitory

  18. Human Placenta Is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells throughout Development

    NARCIS (Netherlands)

    C. Robin (Catherine); K. Bollerot (Karine); S.C. Mendes (Sandra); E. Haak (Esther); M. Crisan (Mihaela); F. Cerisoli (Francesco); I. Lauw (Ivoune); P. Kaimakis (Polynikis); R.J.J. Jorna (Ruud); M. Vermeulen (Mark); M.H. Kayser (Manfred); R. van der Linden (Reinier); P. Imanirad (Parisa); M.M.A. Verstegen (Monique); H. Nawaz-Yousaf (Humaira); N. Papazian (Natalie); E.A.P. Steegers (Eric); T. Cupedo (Tom); E.A. Dzierzak (Elaine)

    2009-01-01

    textabstractHematopoietic stem cells (HSCs) are responsible for the life-long production of the blood system and are pivotal cells in hematologic transplantation therapies. During mouse and human development, the first HSCs are produced in the aorta-gonad-mesonephros region. Subsequent to this emerg

  19. Current challenges in dedifferentiated fat cells research.

    Science.gov (United States)

    Shah, Mickey; George, Richard L; Evancho-Chapman, M Michelle; Zhang, Ge

    2016-07-02

    Dedifferentiated fat cells show great promises as a novel cell source for stem cell research. It has many advantages when used for cell-based therapeutics including abundance, pluripotency, and safety. However, there are many obstacles researchers need to overcome to make the next big move in DFAT cells research. In this review, we summarize the current main challenges in DFAT cells research including cell culture purity, phenotypic properties, and dedifferentiation mechanisms. The common methods to produce DFAT cells as well as the cell purity issue during DFAT cell production have been introduced. Current approaches to improve DFAT cell purity have been discussed. The phenotypic profile of DFAT cells have been listed and compared with other stem cells. Further studies on elucidating the underlying dedifferentiation mechanisms will dramatically advance DFAT cell research.

  20. Current-Enhanced Quantum Well Solar Cells

    Institute of Scientific and Technical Information of China (English)

    LOU Chao-Gang; SUN Qiang; XU Jun; ZHANG Xiao-Bing; LEI Wei; WANG Bao-Ping; CHEN Wen-Jun; QIAO Zai-Xiang

    2006-01-01

    We present the experimental results that demonstrate the enhancement of the short-circuit current of quantum well solar cells. The spectral response shows that the introduction of quantum wells extends the absorption spectrum of solar cells. The current densities under different truncated spectrums significantly increase, showing that quantum well solar cells are suitable to be the middle cells of GaInP/GaAs/Ge triple-junction solar cells to increase their overall conversion efficiency.

  1. Market survey of fuel cells in Mexico: Niche for low power portable systems

    Science.gov (United States)

    Ramírez-Salgado, Joel; Domínguez-Aguilar, Marco A.

    This work provides an overview of the potential market in Mexico for portable electronic devices to be potentially powered by direct methanol fuel cells. An extrapolation method based on data published in Mexico and abroad served to complete this market survey. A review of electronics consumption set the basis for the future forecast and technology assimilation. The potential market for fuel cells for mobile phones in Mexico will be around 5.5 billion USD by 2013, considering a cost of 41 USD per cell in a market of 135 million mobile phones. Likewise, the market for notebook computers, PDAs and other electronic devices will likely grow in the future, with a combined consumption of fuel cell technology equivalent to 1.6 billion USD by 2014.

  2. Stem Cells and Tissue Niche: Two Faces of the Same Coin of Muscle Regeneration

    Science.gov (United States)

    Scicchitano, Bianca Maria; Sica, Gigliola; Musarò, Antonio

    2016-01-01

    Capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program. However, muscle regeneration is severely compromised in several pathological conditions. It is likely that the restricted tissue repair program under pathological conditions is due to either progressive loss of stem cell populations or to missing signals that limit the damaged tissues to efficiently activate a regenerative program. It is therefore plausible that loss of control over these cell fates might lead to a pathological cell transdifferentiation, limiting the ability of a pathological muscle to sustain an efficient regenerative process. The critical role of microenvironment on stem cells activity and muscle regeneration is discussed. PMID:28078070

  3. Stem cells and tissue niche: two faces of the same coin of muscle regeneration

    Directory of Open Access Journals (Sweden)

    Bianca Maria Scicchitano

    2016-11-01

    Full Text Available Capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program. However, muscle regeneration is severely compromised in several pathological conditions. It is likely that the restricted tissue repair program under pathological conditions is due to either progressive loss of stem cell populations or to missing signals that limit the damaged tissues to efficiently activate a regenerative program. It is therefore plausible that loss of control over these cell fates might lead to a pathological cell transdifferentiation, limiting the ability of a pathological muscle to sustain an efficient regenerative process. The critical role of microenvironment on stem cells activity and muscle regeneration is discussed.

  4. Market survey of fuel cells in Mexico: Niche for low power portable systems

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez-Salgado, Joel [Programa de Ingenieria Molecular, Instituto Mexicano del Petroleo, Eje Lazaro Cardenas No 152, 07730 D. F. (Mexico); Dominguez-Aguilar, Marco A. [Laboratorio de Sintesis Quimica y Electroquimica, Instituto Mexicano del Petroleo, Eje Lazaro Cardenas No 152, 07730 D. F. (Mexico)

    2009-01-15

    This work provides an overview of the potential market in Mexico for portable electronic devices to be potentially powered by direct methanol fuel cells. An extrapolation method based on data published in Mexico and abroad served to complete this market survey. A review of electronics consumption set the basis for the future forecast and technology assimilation. The potential market for fuel cells for mobile phones in Mexico will be around 5.5 billion USD by 2013, considering a cost of 41 USD per cell in a market of 135 million mobile phones. Likewise, the market for notebook computers, PDAs and other electronic devices will likely grow in the future, with a combined consumption of fuel cell technology equivalent to 1.6 billion USD by 2014. (author)

  5. Pericyte actomyosin-mediated contraction at the cell-material interface can modulate the microvascular niche

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sunyoung; Zeiger, Adam; Maloney, John M; Van Vliet, Krystyn J [Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Kotecki, Maciej; Herman, Ira M, E-mail: krystyn@mit.ed, E-mail: ira.herman@tufts.ed [Department of Physiology, Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111 (United States)

    2010-05-19

    Pericytes physically surround the capillary endothelium, contacting and communicating with associated vascular endothelial cells via cell-cell and cell-matrix contacts. Pericyte-endothelial cell interactions thus have the potential to modulate growth and function of the microvasculature. Here we employ the experimental finding that pericytes can buckle a freestanding, underlying membrane via actin-mediated contraction. Pericytes were cultured on deformable silicone substrata, and pericyte-generated wrinkles were imaged via both optical and atomic force microscopy (AFM). The local stiffness of subcellular domains both near and far from these wrinkles was investigated by using AFM-enabled nanoindentation to quantify effective elastic moduli. Substratum buckling contraction was quantified by the normalized change in length of initially flat regions of the substrata (corresponding to wrinkle contour lengths), and a model was used to relate local strain energies to pericyte contractile forces. The nature of pericyte-generated wrinkling and contractile protein-generated force transduction was further explored by the addition of pharmacological cytoskeletal inhibitors that affected contractile forces and the effective elastic moduli of pericyte domains. Actin-mediated forces are sufficient for pericytes to exert an average buckling contraction of 38% on the elastomeric substrata employed in these in vitro studies. Actomyosin-mediated contractile forces also act in vivo on the compliant environment of the microvasculature, including the basement membrane and other cells. Pericyte-generated substratum deformation can thus serve as a direct mechanical stimulus to adjacent vascular endothelial cells, and potentially alter the effective mechanical stiffness of nonlinear elastic extracellular matrices, to modulate pericyte-endothelial cell interactions that directly influence both physiologic and pathologic angiogenesis.

  6. CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7- and IL-15-dependent niches.

    Science.gov (United States)

    Jung, Yong Woo; Kim, Hyun Gyung; Perry, Curtis J; Kaech, Susan M

    2016-07-19

    C-C receptor 7 (CCR7) is important to allow T cells and dendritic cells to migrate toward CCL19- and CCL21-producing cells in the T-cell zone of the spleen and lymph nodes. The role of this chemokine receptor in regulating the homeostasis of effector and memory T cells during acute viral infection is poorly defined, however. In this study, we show that CCR7 expression alters memory CD8 T-cell homeostasis following lymphocytic choriomeningitis virus infection. Greater numbers of CCR7-deficient memory T cells were formed and maintained compared with CCR7-sufficient memory T cells, especially in the lung and bone marrow. The CCR7-deficient memory T cells also displayed enhanced rates of homeostatic turnover, which may stem from increased exposure to IL-15 as a consequence of reduced exposure to IL-7, because removal of IL-15, but not of IL-7, normalized the numbers of CCR7-sufficient and CCR7-deficient memory CD8 T cells. This result suggests that IL-15 is the predominant cytokine supporting augmentation of the CCR7(-/-) memory CD8 T-cell pool. Taken together, these data suggest that CCR7 biases memory CD8 T cells toward IL-7-dependent niches over IL-15-dependent niches, which provides insight into the homeostatic regulation of different memory T-cell subsets.

  7. Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

    Science.gov (United States)

    de Almeida Sassi, Felipe; Lunardi Brunetto, Algemir; Schwartsmann, Gilberto; Roesler, Rafael; Abujamra, Ana Lucia

    2012-01-01

    Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment. PMID:22973309

  8. Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus.

    Science.gov (United States)

    Volkenstein, Stefan; Oshima, Kazuo; Sinkkonen, Saku T; Corrales, C Eduardo; Most, Sam P; Chai, Renjie; Jan, Taha A; van Amerongen, Renée; Cheng, Alan G; Heller, Stefan

    2013-08-27

    In the cochlear nucleus (CN), the first central relay of the auditory pathway, the survival of neurons during the first weeks after birth depends on afferent innervation from the cochlea. Although input-dependent neuron survival has been extensively studied in the CN, neurogenesis has not been evaluated as a possible mechanism of postnatal plasticity. Here we show that new neurons are born in the CN during the critical period of postnatal plasticity. Coincidently, we found a population of neural progenitor cells that are controlled by a complex interplay of Wnt, Notch, and TGFβ/BMP signaling, in which low levels of TGFβ/BMP signaling are permissive for progenitor proliferation that is promoted by Wnt and Notch activation. We further show that cells with activated Wnt signaling reside in the CN and that these cells have high propensity for neurosphere formation. Cochlear ablation resulted in diminishment of progenitors and Wnt/β-catenin-active cells, suggesting that the neonatal CN maintains an afferent innervation-dependent population of progenitor cells that display active canonical Wnt signaling.

  9. 植物根尖干细胞微环境的遗传调控%Genetical Regulation of Stem Cell Niche Maintenance in Plant Roots

    Institute of Scientific and Technical Information of China (English)

    徐庞连; 阳成伟; 李春鑫; 袁东柯

    2013-01-01

    干细胞微环境是平衡干细胞自我更新、多向分化和压力响应的微环境.近年来,通过大量的突变体筛选和现代的影像技术,植物根尖干细胞微环境特化和维持的调控机制取得了很大进展.该文着重概述转录因子网络、激素信号转导、染色质因子和基因组组织因子在调控根尖干细胞微环境中的作用.%Stem cell niches are dynamic microenvironments that balance stem cell renewal, differentiation and the engagement of programs in response to stress. Recent works have improved our understanding of the mechanisms responsible for the specification and maintenance of stem cell niche in the root meristems using mutant screening and live imaging. In this review, we summarize recent findings regarding the role of transcriptional networks, hormone signaling, chromatin factors and genome organization factors in regulating root stem cell niche.

  10. Current considerations about Merkel cells.

    Science.gov (United States)

    Lucarz, Annie; Brand, Gerard

    2007-05-01

    Since the discovery of Merkel cells by Friedrich S. Merkel in 1875, knowledge of their structure has increased with the progression of new technologies such as electron and laser microscopy, and immunohistochemical techniques. For most vertebrates, Merkel cells are located in the basal layer of the epidermis and characterized by dense-core granules that contain a variety of neuropeptides, plasma membrane spines and cytoskeletal filaments consisting of cytokeratins and desmosomes. The presence of the two latter structures would suggest that Merkel cells originate from the epidermis rather than from the neural crest, even though such a hypothesis is not unanimously accepted. The function of the Merkel cell is also very controversial. For a long time, it has been accepted that Merkel cells with associated nerve terminals act as mechanoreceptors although the transduction mechanism has not yet been elucidated. Merkel cells that do not make contact with nerve terminals have an endocrine function. The present review aims to shed new and comparative light on this field with an attempt to investigate the stimuli that Merkel cells are able to perceive.

  11. The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.

    Science.gov (United States)

    Dovere, Lisa; Fera, Stefania; Grasso, Margherita; Lamberti, Dante; Gargioli, Cesare; Muciaccia, Barbara; Lustri, Anna Maria; Stefanini, Mario; Vicini, Elena

    2013-01-01

    In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF), a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  12. The niche-derived glial cell line-derived neurotrophic factor (GDNF induces migration of mouse spermatogonial stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Lisa Dovere

    Full Text Available In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF, a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  13. Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells

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    Christopher J. Sontag

    2014-05-01

    Full Text Available The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how NSCs differentially respond to intact versus damaged CNS. Furthermore, single, terminal histological endpoints predominate, providing limited insight into the spatiotemporal dynamics of NSC engraftment and migration. We investigated the early and long-term engraftment dynamics of human CNS stem cells propagated as neurospheres (hCNS-SCns following transplantation into uninjured versus subacutely injured spinal cords of immunodeficient NOD-scid mice. We stereologically quantified engraftment, survival, proliferation, migration, and differentiation at 1, 7, 14, 28, and 98 days posttransplantation, and identified injury-dependent alterations. Notably, the injured microenvironment decreased hCNS-SCns survival, delayed and altered the location of proliferation, influenced both total and fate-specific migration, and promoted oligodendrocyte maturation.

  14. AngioMap is a novel image analysis algorithm for assessment of plasma cell distribution within bone marrow vascular niche.

    Science.gov (United States)

    Salama, Mohamed E; Lange, Holger; Tripp, Sheryl R; Kohan, Jessica; Landis, Nicholas D; Krueger, Joseph S; Potts, Steven J

    2014-08-01

    The ability to characterize distribution of neoplastic hematopoietic cells and their progenitors in their native microenvironment is emerging as an important challenge and potential therapeutic target in many disease areas, including multiple myeloma. In multiple myeloma, bone marrow (BM) angiogenesis is typically increased and microvessel density is a known indicator of poor prognosis. However, the difficulty of consistently measuring 3D vessels from 2D cut sections has previously limited the study of spatial distribution of plasma cells (PC) and their interaction with BM microenvironment. The aim of the study is to report a novel method to study myeloma cells spatial distribution within their hematopoietic niche context using readily available tissue sections and standard histology approaches. We utilized a novel whole-tissue image analysis approach to identify vessels, and then applied computational grown regions extended out from each vessel at 15, 35, 55, 75, and 100 μm to identify the spatial distribution of PC on CD34/CD138 double-stained core biopsy slides. Percent PC to total cells (TC) was significantly higher at <15 μm distance compared with those at 16 to 35, 36 to 55, 56 to 75, and 76 to 100 μm distance (P=0.0001). Similarly, PC/TC at <35 μm region was significantly higher compared with 36 to 55 (P=0.0001), 56 to 75 (P≤0.0001), and 76 to 100 (P=0.0002) μm distances. The mean PC/TC differences in the spatial gradient of 36 to 55, 56 to 75, and 76 to 100 μm distance regions were not significant. Our findings suggest possible preferential advantage to neoplastic PC in the proximity of blood vessels compared with other hematopoietic marrow cells. We demonstrate the feasibility of analyzing the spatial distribution of PC, and possibly other hematopoietic/stem cells in their microenvironment, as characterized by the distance to vessels in BM using a novel image analysis approach.

  15. Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.

    Science.gov (United States)

    Medinger, M; Krenger, W; Jakab, A; Halter, J; Buser, A; Bucher, C; Passweg, J; Tzankov, A

    2015-11-01

    The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.

  16. Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells

    Directory of Open Access Journals (Sweden)

    Giacomo Palazzolo

    2016-01-01

    Full Text Available The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs. We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C, known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis.

  17. Metabolic diversity and ecological niches of Achromatium populations revealed with single-cell genomic sequencing

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    Muammar eMansor

    2015-08-01

    Full Text Available Large, sulfur-cycling, calcite-precipitating bacteria in the genus Achromatium represent a significant proportion of bacterial communities near sediment-water interfaces throughout the world. Our understanding of their potentially crucial roles in calcium, carbon, sulfur, nitrogen, and iron cycling is limited because they have not been cultured or sequenced using environmental genomics approaches to date. We utilized single-cell genomic sequencing to obtain one incomplete and two nearly complete draft genomes for Achromatium collected at Warm Mineral Springs, FL. Based on 16S rRNA gene sequences, the three cells represent distinct and relatively distant Achromatium populations (91-92% identity. The draft genomes encode key genes involved in sulfur and hydrogen oxidation; oxygen, nitrogen and polysulfide respiration; carbon and nitrogen fixation; organic carbon assimilation and storage; chemotaxis; twitching motility; antibiotic resistance; and membrane transport. Known genes for iron and manganese energy metabolism were not detected. The presence of pyrophosphatase and vacuolar (V-type ATPases, which are generally rare in bacterial genomes, suggests a role for these enzymes in calcium transport, proton pumping, and/or energy generation in the membranes of calcite-containing inclusions.

  18. Understanding the application niche of microbial fuel cells in a cheese wastewater treatment process.

    Science.gov (United States)

    Kelly, Patrick T; He, Zhen

    2014-04-01

    Identifying proper application of microbial fuel cell (MFC) technology and understanding how MFCs can be effectively integrated into the existing wastewater treatment process is critical to further development of this technology. In this study, four identical MFCs were used to treat the wastes sampled from different stages of a cheese wastewater treatment process, and both treatment performance and energy balance were examined. The two MFCs treating liquid wastes achieved more than 80% removal of total chemical oxygen demand (TCOD), while the other two MFCs fed with sludge or cheese whey removed about 60% of TCOD. The MFC-2 treating the dissolved air flotation effluent generated the highest Coulombic efficiency of 27.2±3.6% and the highest power density of 3.2±0.3Wm(-3), and consumed the least amount of energy of 0.11kWhm(-3), indicating that MFCs may be more suitable for treating low-strength wastewater in terms of both treatment and energy performance.

  19. A spin cell for spin current.

    Science.gov (United States)

    Sun, Qing-feng; Guo, Hong; Wang, Jian

    2003-06-27

    We propose and investigate a spin-cell device which provides the necessary spin-motive force to drive a spin current for future spintronic circuits. Our spin cell has four basic characteristics: (i) it has two poles so that a spin current flows in from one pole and out from the other pole, and in this way a complete spin circuit can be established; (ii) it has a source of energy to drive the spin current; (iii) it maintains spin coherence so that a sizable spin current can be delivered; (iv) it drives a spin current without a charge current. The proposed spin cell for spin current should be realizable using technologies presently available.

  20. Why do niches develop in Caesarean uterine scars? Hypotheses on the aetiology of niche development.

    Science.gov (United States)

    Vervoort, A J M W; Uittenbogaard, L B; Hehenkamp, W J K; Brölmann, H A M; Mol, B W J; Huirne, J A F

    2015-12-01

    Caesarean section (CS) results in the occurrence of the phenomenon 'niche'. A 'niche' describes the presence of a hypoechoic area within the myometrium of the lower uterine segment, reflecting a discontinuation of the myometrium at the site of a previous CS. Using gel or saline instillation sonohysterography, a niche is identified in the scar in more than half of the women who had had a CS, most with the uterus closed in one single layer, without closure of the peritoneum. An incompletely healed scar is a long-term complication of the CS and is associated with more gynaecological symptoms than is commonly acknowledged. Approximately 30% of women with a niche report spotting at 6-12 months after their CS. Other reported symptoms in women with a niche are dysmenorrhoea, chronic pelvic pain and dyspareunia. Given the association between a niche and gynaecological symptoms, obstetric complications and potentially with subfertility, it is important to elucidate the aetiology of niche development after CS in order to develop preventive strategies. Based on current published data and our observations during sonographic, hysteroscopic and laparoscopic evaluations of niches we postulate some hypotheses on niche development. Possible factors that could play a role in niche development include a very low incision through cervical tissue, inadequate suturing technique during closure of the uterine scar, surgical interventions that increase adhesion formation or patient-related factors that impair wound healing or increase inflammation or adhesion formation.

  1. Temporally and spatially dynamic germ cell niches in Botryllus schlosseri revealed by expression of a TGF-beta family ligand and vasa

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    Adam D. Langenbacher

    2016-04-01

    Full Text Available Abstract Background Germ cells are specified during early development and are responsible for generating gametes in the adult. After germ cells are specified, they typically migrate to a particular niche in the organism where they reside for the remainder of its lifetime. For some model organisms, the specification and migration of germ cells have been extensively studied, but how these events occur in animals that reproduce both sexually and asexually is not well understood. Results We have identified a novel TGF-β family member in Botryllus schlosseri, tgfβ-f, and found that it is expressed by follicle cell progenitors and the differentiated follicle and support cells surrounding the maturing gametes. Using the expression of tgfβ-f and the germ cell marker vasa, we have found that nearly all germ cells in Botryllus are associated with tgfβ-f-expressing follicle progenitors in clusters consisting solely of those two cell types. These clusters were mostly small, consisting of ten or fewer cells, and generally contained between a 2:1 and 1:1 ratio of follicle progenitors to germ cells. Clusters of germ and follicle progenitor cells were primarily localized to niches in the primary and secondary buds, but could also be found in other locations including the vasculature. We analyzed the location of germ cell clusters throughout the asexual life cycle of Botryllus and found that at the stage when germ cells are first detected in the secondary bud niche, a dramatic change in the size and location of germ/follicle cell clusters also occurred. Conclusions Our findings suggest that germ/follicle cell clusters have predictable migratory patterns during the weekly asexual developmental cycle in Botryllus. An increased number of small clusters and the presence of clusters in the vasculature coinciding with the appearance of clusters in the secondary bud suggest that fragmentation of clusters and the migration of smaller clusters through the vasculature

  2. Disequilibrium of BMP2 levels in the breast stem cell niche launches epithelial transformation by overamplifying BMPR1B cell response.

    Science.gov (United States)

    Chapellier, Marion; Bachelard-Cascales, Elodie; Schmidt, Xenia; Clément, Flora; Treilleux, Isabelle; Delay, Emmanuel; Jammot, Alexandre; Ménétrier-Caux, Christine; Pochon, Gaëtan; Besançon, Roger; Voeltzel, Thibault; Caron de Fromentel, Claude; Caux, Christophe; Blay, Jean-Yves; Iggo, Richard; Maguer-Satta, Véronique

    2015-02-10

    Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.

  3. Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response

    Directory of Open Access Journals (Sweden)

    Marion Chapellier

    2015-02-01

    Full Text Available Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.

  4. Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response

    Science.gov (United States)

    Chapellier, Marion; Bachelard-Cascales, Elodie; Schmidt, Xenia; Clément, Flora; Treilleux, Isabelle; Delay, Emmanuel; Jammot, Alexandre; Ménétrier-Caux, Christine; Pochon, Gaëtan; Besançon, Roger; Voeltzel, Thibault; Caron de Fromentel, Claude; Caux, Christophe; Blay, Jean-Yves; Iggo, Richard; Maguer-Satta, Véronique

    2015-01-01

    Summary Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer. PMID:25601208

  5. PTPN13 and β-Catenin Regulate the Quiescence of Hematopoietic Stem Cells and Their Interaction with the Bone Marrow Niche

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    Guillermo López-Ruano

    2015-10-01

    Full Text Available The regulation of hematopoietic stem cells (HSCs depends on the integration of the multiple signals received from the bone marrow niche. We show the relevance of the protein tyrosine phosphatase PTPN13 and β-catenin as intracellular signaling molecules to control HSCs adhesiveness, cell cycling, and quiescence. Lethally irradiated mice transplanted with Lin– bone marrow cells in which PTPN13 or β-catenin had been silenced showed a significant increase of long-term (LT and short-term (ST HSCs. A decrease in cycling cells was also found, together with an increase in quiescence. The decreased expression of PTPN13 or β-catenin was linked to the upregulation of several genes coding for integrins and several cadherins, explaining the higher cell adhesiveness. Our data are consistent with the notion that the levels of PTPN13 and β-catenin must be strictly regulated by extracellular signaling to regulate HSC attachment to the niche and the balance between proliferation and quiescence.

  6. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Beck, Mette

    2015-01-01

    the metastatic spread of tumor cells is the S100A4 protein. S100A4 is known as an inducer of inflammatory processes and has been shown to attract T-cells to the primary tumor and to the pre-metastatic niche. The present study aims to examine the immunomodulatory role of S100A4 in vivo and in vitro and assess...... the mode of action of 6B12, a S100A4 neutralizing antibody. METHODS: The therapeutic effect of the 6B12 antibody was evaluated in two different mouse models. First, in a model of spontaneous breast cancer we assessed the dynamics of tumor growth and metastasis. Second, in a model of metastatic niche...... that the S100A4 protein alters the expression of transcription factor and signal transduction pathway genes involved in the T-cell lineage differentiation. T-cells challenged with S100A4 demonstrated reduced proportion of Th1-polarized cells shifting the Th1/Th2 balance towards the Th2 pro...

  7. Signaling pathways in self-renewing hematopoietic and leukemic stem cells : do all stem cells need a niche?

    NARCIS (Netherlands)

    Rizo, Aleksandra; Vellenga, Edo; de Haan, Gerald; Schuringa, Jan Jacob

    2006-01-01

    Many adult tissue stem cells, such as the cells of the hematopoietic system, gastrointestinal epithelium, brain, epidermis, mammary gland and lung have now been identified, all of them fulfilling a crucial role in supplying organisms with mature cells during normal homeostasis as well as in times of

  8. Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor Initiating Cells

    Science.gov (United States)

    2013-06-01

    redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples...collagenase (300 U/ml)/hyaluronidase (100 U/ml) solution followed by sequential filtration . Single cell suspensions were cultured on ultra low attachment...Curriculum Vitae Carolyn Marsden 6 Assistant Professor Research Associate Professor Department of Pharmacology Department of Microbiology and

  9. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    Science.gov (United States)

    2010-01-01

    Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs. PMID:20663133

  10. Characterization of drCol 15a1b: a novel component of the stem cell niche in the zebrafish retina.

    Science.gov (United States)

    Gonzalez-Nunez, Veronica; Nocco, Valentina; Budd, Aidan

    2010-08-01

    There is a clear need to develop novel tools to help improve our understanding of stem cell biology, and potentially also the utility of stem cells in regenerative medicine. We report the cloning, functional, and bioinformatic characterization of a novel stem cell marker in the zebrafish retina, drCol 15a1b. The expression pattern of drCol 15a1b is restricted to stem cell niches located in the central nervous system, whereas other collagen XVs are associated with muscle and endothelial tissues. Knocking down drCol 15a1b expression causes smaller eyes, ear defects, and brain edema. Microscopic analysis reveals enhanced proliferation in the morphant eye, with many mitotic nuclei located in the central retina, together with a delayed differentiation of the mature retinal cell types. Besides, several markers known to be expressed in the ciliary marginal zone display broader expression areas in morpholino-injected embryos, suggesting an anomalous diffusion of signaling effectors from the sonic hedgehog and notch pathways. These results indicate that drCol 15a1b is a novel stem cell marker in the central nervous system that has a key role in homing stem cells into specialized niches in the adult organism. Moreover, mutations in the hCol 18a1 gene are responsible for the Knobloch syndrome, which affects brain and retinal structures, suggesting that drCol 15a1b may function similarly to mammalian Col 18a1. Thus, our results shed new light on the signaling pathways that underlie the maintenance of stem cells in the adult organism while helping us to understand the role of extracellular matrix proteins in modulating the signals that determine stem cell differentiation, cell cycle exit and apoptosis.

  11. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    Science.gov (United States)

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive.

  12. Ionic currents in crustacean neurosecretory cells.

    Science.gov (United States)

    Onetti, C G; García, U; Valdiosera, R F; Aréchiga, H

    1990-11-01

    1. The patterns of electrical activity and membrane characteristics of a population of neurosecretory-cell somata in the X-organ of the crayfish were investigated with microelectrodes and whole-cell, voltage-clamp techniques. Some neurons (56%) were silent but could be excited by intracellular current injection: other cells showed spontaneous tonic activity (35%), and some had spontaneous bursting activity (9%). The spiking activity was abolished by tetrodotoxin (TTX) exposure and by severing the axon near the cell body. After axotomy, only a small, slow, regenerative depolarization remained that could be blocked by Cd2+. 2. Under voltage clamp the steady-state I-V curve in low [Ca2+]i (9 X 10(-9) M) showed a slope conductance of 16.7 +/- 3.9 (SD) nS (n = 10) at -50 mV and zero current potential of -50.1 +/- 7.7 mV. In current-clamp mode these neurons were either silent or fired tonically. With high [Ca2+]i (1.7 X 10(-6) M) both the slope conductance and inward and outward currents were reduced. In some neurons high [Ca2+]i reveals a negative slope resistance in the range of -46 to -41 mV. It could be supressed by removing [Na+]o, but it was TTX insensitive. These are the neurons that under current clamp showed bursting activity. 3. The main inward current in cell somata was a Ca2+ current of 2 +/- 0.6 nA (n = 18), activated at -40 mV and peaking at 20 mV. It showed relaxation with prolonged pulses. No Na(+)-dependent, TTX-sensitive inward currents were recorded with short (100-ms) pulses in axotomized neurons. 4. Two outward currents could be distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Current efficiency in the chlorate cell process

    Directory of Open Access Journals (Sweden)

    Spasojević Miroslav D.

    2014-01-01

    Full Text Available A mathematical model has been set up for current efficiency in a chlorate cell acting as an ideal electrochemical tubular reactor with a linear increase in hypochlorite concentration from the entrance to the exit. Good agreement was found between the results on current efficiency experimentally obtained under simulated industrial chlorate production conditions and the theoretical values provided by the mathematical model. [Projekat Ministarstva nauke Republike Srbije, br. 172057 i br. 172062

  14. Current progress with primate embryonic stem cells.

    Science.gov (United States)

    Byrne, James A; Mitalipov, Shoukhrat M; Wolf, Don P

    2006-05-01

    Embryonic stem cells (ESCs) can proliferate indefinitely, maintain an undifferentiated pluripotent state and differentiate into any cell type. Differentiation of ESCs into various specific cell-types may be able to cure or alleviate the symptoms of various degenerative diseases. Unresolved issues regarding maintaining function, possible apoptosis and tumor formation in vivo mean a prudent approach should be taken towards advancing ESCs into human clinical trials. Rhesus macaques provide the ideal model organism for testing the feasibility, efficacy and safety of ESC based therapies and significant numbers of primate ESC lines are now available. In this review, we will summarize progress in evaluating the genetic and epigenetic integrity of primate ESCs, examine their current use in pre-clinical trials and discuss the potential of producing ESC-derived cell populations that are genetically identical (isogenic) to the host by somatic cell nuclear transfer.

  15. Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche.

    Science.gov (United States)

    Sánchez, Catherine A; Andahur, Eliana I; Valenzuela, Rodrigo; Castellón, Enrique A; Fullá, Juan A; Ramos, Christian G; Triviño, Juan C

    2016-01-26

    The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.

  16. Climatic niche divergence or conservatism? Environmental niches and range limits in ecologically similar damselflies.

    Science.gov (United States)

    Wellenreuther, Maren; Larson, Keith W; Svensson, Erik I

    2012-06-01

    The factors that determine species' range limits are of central interest to biologists. One particularly interesting group comprises odonates (dragonflies and damselflies), which show large differences in secondary sexual traits and respond quickly to climatic factors, but often have minor interspecific niche differences, challenging models of niche-based species coexistence. We quantified the environmental niches at two geographic scales to understand the ecological causes of northern range limits and the coexistence of two congeneric damselflies (Calopteryx splendens and C. virgo). Using environmental niche modeling, we quantified niche divergence first across the whole geographic range in Fennoscandia, and second only in the sympatric part of this range. We found evidence for interspecific divergence along the environmental axes of temperature and precipitation across the northern range in Fennoscandia, suggesting that adaptation to colder and wetter climate might have allowed C. virgo to expand farther north than C. splendens. However, in the sympatric zone in southern Fennoscandia we found only negligible and nonsignificant niche differences. Minor niche differences in sympatry lead to frequent encounters and intense interspecific sexual interactions at the local scale of populations. Nevertheless, niche differences across Fennoscandia suggest that species differences in physiological tolerances limit range expansions northward, and that current and future climate could have large effects on the distributional ranges of these and ecologically similar insects.

  17. Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids.

    Science.gov (United States)

    Aagesen, Lone; Biganzoli, Fernando; Bena, Julia; Godoy-Bürki, Ana C; Reinheimer, Renata; Zuloaga, Fernando O

    2016-01-01

    Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.

  18. Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche.

    Science.gov (United States)

    Kobolak, Julianna; Dinnyes, Andras; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Ali

    2016-04-15

    Mesenchymal stem cells (MSCs) are multipotent stem cells. Although they were originally identified in bone marrow and described as 'marrow stromal cells', they have since been identified in many other anatomical locations in the body. MSCs can be isolated from bone marrow, adipose tissue, umbilical cord and other tissues but the richest tissue source of MSCs is fat. Since they are adherent to plastic, they may be expanded in vitro. MSCs have a distinct morphology and express a specific set of CD (cluster of differentiation) molecules. The phenotypic pattern for the identification of MSCs cells requires expression of CD73, CD90, and CD105 and lack of CD34, CD45, and HLA-DR antigens. Under appropriate micro-environmental conditions MSCs can proliferate and give rise to other cell types. Therefore, they are ideally suited for the treatment of systemic inflammatory and autoimmune conditions. They have also been implicated as key players in regenerating injured tissue following injury and trauma. MSC populations isolated from adipose tissue may also contain regulatory T (Treg) cells, which have the capacity for modulating the immune system. The immunoregulatory and regenerative properties of MSCs make them ideal for use as therapeutic agents in vivo. In this paper we review the literature on the identification, phenotypic characterization and biological properties of MSCs and discuss their potential for applications in cell therapy and regenerative medicine. We also discuss strategies for biomaterial micro-engineering of the stem cell niche.

  19. Sulfur nutrient availability regulates root elongation by affecting root indole-3-acetic acid levels and the stem cell niche

    Institute of Scientific and Technical Information of China (English)

    Qing Zhao; Yu Wu; Lei Gao; Jun Ma; Chuan-You Li; Cheng-Bin Xiang

    2014-01-01

    Sulfur is an essential macronutrient for plants with numerous biological functions. However, the influence of sulfur nutrient availability on the regulation of root development remains largely unknown. Here, we report the response of Arabidopsis thaliana L. root development and growth to different levels of sulfate, demonstrating that low sulfate levels promote the primary root elongation. By using various reporter lines, we examined in vivo IAA level and distribution, cel division, and root meristem in response to different sulfate levels. Meanwhile the dynamic changes of in vivo cysteine, glutathione, and IAA levels were measured. Root cysteine, glutathione, and IAA levels are positively correlated with external sulfate levels in the physiological range, which eventual y affect root system architecture. Low sulfate levels also downregulate the genes involved in auxin biosynthesis and transport, and elevate the accumulation of PLT1 and PLT2. This study suggests that sulfate level affects the primary root elongation by regulating the endogenous auxin level and root stem cel niche maintenance.

  20. CXCR4(+) CD45(-) Cells are Niche Forming for Osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 Signaling Pathways in Bone Marrow.

    Science.gov (United States)

    Goto, Yoh; Aoyama, Mineyoshi; Sekiya, Takeo; Kakita, Hiroki; Waguri-Nagaya, Yuko; Miyazawa, Ken; Asai, Kiyofumi; Goto, Shigemi

    2016-06-24

    Bone homeostasis comprises the balance between bone-forming osteoblasts and bone-resorbing osteoclasts (OCs), with an acceleration of osteoclastic bone resorption leading to osteoporosis. OCs can be generated from bone marrow cells (BMCs) under the tightly regulated local bone environment. However, it remained difficult to identify the critical cells responsible for providing an osteoclastogenesis niche. In this study, we used a fluorescence-activated cell sorting technique to determine the cell populations important for forming an appropriate microenvironment for osteoclastogenesis and to verify the associated interactions between osteoclast precursor cells and non-OCs. We isolated and removed a small cell population specific for osteoclastogenesis (CXCR4(+) CD45(-) ) from mouse BMCs and cultured the remaining cells with receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage-colony stimulating factor. The resulting cultures showed significantly less large osteoclast formation. Quantitative RT-PCR analysis revealed that these CXCR4(+) CD45(-) cells expressed low levels of RANK and RANKL, but high levels of critical chemokines including stromal cell derived factor 1 (SDF-1), chemokine (C-X-C motif) ligand 7 (CXCL7), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). Furthermore, an SDF-1-specific antibody strongly suppressed OC formation in RAW264.7 cells and antibodies against SDF-1, CXCL7, and CX3CL1 suppressed OC formation in BMCs. These results suggest that isolated CXCR4(+) CD45(-) cells support an appropriate microenvironment for osteoclastogenesis with a direct effect on the cells expressing SDF-1, CXCL7, and CX3CL1 receptors. The regulation of CXCR4(+) CD45(-) cell function might therefore inform therapeutic strategies for diseases involving loss of bone homeostasis. Stem Cells 2016.

  1. Current techniques for visualizing RNA in cells

    Science.gov (United States)

    Mannack, Lilith V.J.C.; Eising, Sebastian; Rentmeister, Andrea

    2016-01-01

    Labeling RNA is of utmost interest, particularly in living cells, and thus RNA imaging is an emerging field. There are numerous methods relying on different concepts ranging from hybridization-based probes, over RNA-binding proteins to chemo-enzymatic modification of RNA. These methods have different benefits and limitations. This review aims to outline the current state-of-the-art techniques and point out their benefits and limitations. PMID:27158473

  2. Limbal stem cell transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Atallah MR

    2016-04-01

    Full Text Available Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, Guillermo Amescua Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD. In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on

  3. Microbial Fuel Cells, A Current Review

    Directory of Open Access Journals (Sweden)

    Kelly P. Nevin

    2010-04-01

    Full Text Available Microbial fuel cells (MFCs are devices that can use bacterial metabolism to produce an electrical current from a wide range organic substrates. Due to the promise of sustainable energy production from organic wastes, research has intensified in this field in the last few years. While holding great promise only a few marine sediment MFCs have been used practically, providing current for low power devices. To further improve MFC technology an understanding of the limitations and microbiology of these systems is required. Some researchers are uncovering that the greatest value of MFC technology may not be the production of electricity but the ability of electrode associated microbes to degrade wastes and toxic chemicals. We conclude that for further development of MFC applications, a greater focus on understanding the microbial processes in MFC systems is required.

  4. Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine.

    Science.gov (United States)

    Kingham, Emmajayne; Oreffo, Richard O C

    2013-03-26

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any specialized cell type of the human body, and therefore, ESC/iPSC-derived cell types offer great potential for regenerative medicine. However, key to realizing this potential requires a strong understanding of stem cell biology, techniques to maintain stem cells, and strategies to manipulate cells to efficiently direct cell differentiation toward a desired cell type. As nanoscale science and engineering continues to produce novel nanotechnology platforms, which inform, infiltrate, and impinge on many aspects of everyday life, it is no surprise that stem cell research is turning toward developments in nanotechnology to answer research questions and to overcome obstacles in regenerative medicine. Here we discuss recent advances in ESC and iPSC manipulation using nanomaterials and highlight future challenges within this area of research.

  5. In search of a temporal niche: Environmental factors

    NARCIS (Netherlands)

    Hut, Roelof A.; Kronfeld-Schor, Noga; van der Vinne, Vincent; De la Iglesia, Horacio

    2012-01-01

    Time as an ecological niche variable or "temporal niche" can be defined in the context of the most prominent environmental cycles, including the tidal cycle, the lunar day and month, the solar day, and the earth year. For the current review, we focus on the 24-h domain generated through the earth's

  6. Development and molecular characterization of polymeric micro-nanofibrous scaffold of a defined 3-D niche for in vitro chemosensitivity analysis against acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Nair MS

    2015-05-01

    Full Text Available Maya S Nair,1 Ullas Mony,1 Deepthy Menon,1 Manzoor Koyakutty,1 Neeraj Sidharthan,2 Keechilat Pavithran,2 Shantikumar V Nair,1 Krishnakumar N Menon11Amrita Centre for Nanosciences and Molecular Medicine, 2Department of Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kerala, IndiaAbstract: Standard in vitro drug testing employs 2-D tissue culture plate systems to test anti-leukemic drugs against cell adhesion-mediated drug-resistant leukemic cells that harbor in 3-D bone marrow microenvironments. This drawback necessitates the fabrication of 3-D scaffolds that have cell adhesion-mediated drug-resistant properties similar to in vivo niches. We therefore aimed at exploiting the known property of polyurethane (PU/poly-L-lactic acid (PLLA in forming a micro-nanofibrous structure to fabricate unique, not presented before, as far as we are aware, 3-D micro-nanofibrous scaffold composites using a thermally induced phase separation technique. Among the different combinations of PU/PLLA composites generated, the unique PU/PLLA 60:40 composite displayed micro-nanofibrous morphology similar to decellularized bone marrow with increased protein and fibronectin adsorption. Culturing of acute myeloid leukemia (AML KG1a cells in FN-coated PU/PLLA 60:40 shows increased cell adhesion and cell adhesion-mediated drug resistance to the drugs cytarabine and daunorubicin without changing the original CD34+/CD38-/CD33- phenotype for 168 hours compared to fibronectin tissue culture plate systems. Molecularly, as seen in vivo, increased chemoresistance is associated with the upregulation of anti-apoptotic Bcl2 and the cell cycle regulatory protein p27Kip1leading to cell growth arrest. Abrogation of Bcl2 activity by the Bcl2-specific inhibitor ABT 737 led to cell death in the presence of both cytarabine and daunorubicin, demonstrating that the cell adhesion-mediated drug resistance induced by Bcl2 and p27

  7. Reduced Latency in the Metastatic Niche Contributes to the More Aggressive Phenotype of LM8 Compared to Dunn Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Matthias J. E. Arlt

    2013-01-01

    Full Text Available Metastasis is the major cause of death of osteosarcoma patients and its diagnosis remains difficult. In preclinical studies, however, forced expression of reporter genes in osteosarcoma cells has remarkably improved the detection of micrometastases and, consequently, the quality of the studies. We recently showed that Dunn cells equipped with a lacZ reporter gene disseminated from subcutaneous primary tumors as frequently as their highly metastatic subline LM8, but only LM8 cells grew to macrometastases. In the present time-course study, tail-vein-injected Dunn and LM8 cells settled within 24 h at the same frequency in the lung, liver, and kidney of mice. Furthermore, Dunn cells also grew to macrometastases, but, compared to LM8, with a delay of two weeks in lung and one week in liver and kidney tissue, consistent with prolonged survival of the mice. Dunn- and LM8-cell-derived ovary and spine metastases occurred less frequently. In vitro, Dunn cells showed less invasiveness and stronger contact inhibition and intercellular adhesion than LM8 cells and several cancer- and dormancy-related genes were differentially expressed. In conclusion, Dunn cells, compared to LM8, have a similar capability but a longer latency to form macrometastases and provide an interesting new experimental system to study tumor cell dormancy.

  8. The Multidimensional Nutritional Niche.

    Science.gov (United States)

    Machovsky-Capuska, Gabriel E; Senior, Alistair M; Simpson, Stephen J; Raubenheimer, David

    2016-05-01

    The dietary generalist-specialist distinction plays a pivotal role in theoretical and applied ecology, conservation, invasion biology, and evolution and yet the concept remains poorly characterised. Diets, which are commonly used to define niche breadth, are almost exclusively considered in terms of foods, with little regard for the mixtures of nutrients and other compounds they contain. We use nutritional geometry (NG) to integrate nutrition with food-level approaches to the dietary niche and illustrate the application of our framework in the important context of invasion biology. We use an example that involves a model with four hypothetical nonexclusive scenarios. We additionally show how this approach can provide fresh theoretical insight into the ways nutrition and food choices impact trait evolution and trophic interactions.

  9. Niche Management and its Contribution to Regime Change: The Case of Innovation in Sanitation.

    NARCIS (Netherlands)

    Hegger, D.L.T.; Vliet, van J.M.; Vliet, van B.J.M.

    2007-01-01

    Strategic niche management (SNM) implies that new technologies are applied in so-called niches, in which they are protected against mainstream market selection. A major question currently subject to debate is through which processes niches can bring about any wider changes at the level of socio-tech

  10. The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches

    Directory of Open Access Journals (Sweden)

    Marco Mineo

    2016-06-01

    Full Text Available Long non-coding RNAs (lncRNAs have an undefined role in the pathobiology of glioblastoma multiforme (GBM. These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2 as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal, and hypoxia-dependent molecular reprogramming. Among the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Downregulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome and targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context.

  11. The long non-coding RNA – HIF1A-AS2 facilitates the maintenance of mesenchymal glioblastoma stem-like cells in hypoxic niches

    Science.gov (United States)

    Mineo, Marco; Ricklefs, Franz; Rooj, Arun K.; Lyons, Shawn M.; Ivanov, Pavel; Ansari, Khairul I.; Nakano, Ichiro; Chiocca, E. Antonio; Godlewski, Jakub; Bronisz, Agnieszka

    2016-01-01

    Long-non-coding RNAs (lncRNAs) have an undefined role in the pathobiology of glioblastoma multiforme (GBM). These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs) that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) as a subtype-specific hypoxia inducible lncRNA, up-regulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal and hypoxia-dependent molecular reprogramming. Amongst the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Down-regulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome/targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context. PMID:27264189

  12. Myogenic-specific ablation of Fgfr1 impairs FGF2-mediated proliferation of satellite cells at the myofiber niche but does not abolish the capacity for muscle regeneration

    Directory of Open Access Journals (Sweden)

    Zipora eYablonka-Reuveni

    2015-05-01

    Full Text Available Skeletal muscle satellite cells (SCs are Pax7+ myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury. SC transition through proliferation, differentiation and renewal is governed by the molecular blueprint of the cells as well as by the extracellular milieu at the SC niche. In particular, the role of the fibroblast growth factor (FGF family in regulating SCs during growth and aging is well recognized. Of the several FGFs shown to affect SCs, FGF1, FGF2 and FGF6 proteins have been documented in adult skeletal muscle. These prototypic paracrine FGFs transmit their mitogenic effect through the FGFRs, which are transmembrane tyrosine kinase receptors. Using the mouse model, we show here that of the four FGFRs, only Fgfr1 and Fgfr4 are expressed at relatively high levels in quiescent SCs and their proliferating progeny. To further investigate the role of FGFR1 in adult myogenesis, we have employed a genetic (Cre/loxP approach for myogenic-specific (MyoDCre-driven ablation of Fgfr1. Neither muscle histology nor muscle regeneration following cardiotoxin-induced injury were overtly affected in Fgfr1-ablated mice. This suggests that FGFR1 is not obligatory for SC performance in this acute muscle trauma model, where compensatory growth factor/cytokine regulatory cascades may exist. However, the SC mitogenic response to FGF2 is drastically repressed in isolated myofibers prepared from Fgfr1-ablated mice. Collectively, our study indicates that FGFR1 is important for FGF-mediated proliferation of SCs and its mitogenic role is not compensated by FGFR4 that is also highly expressed in SCs.

  13. Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity

    Directory of Open Access Journals (Sweden)

    Kameliya Vinketova

    2016-01-01

    Full Text Available The human decidua is a specialized tissue characterized by embryo-receptive properties. It is formed during the secretory phase of menstrual cycle from uterine mucosa termed endometrium. The decidua is composed of glands, immune cells, blood and lymph vessels, and decidual stromal cells (DSCs. In the process of decidualization, which is controlled by oestrogen and progesterone, DSCs acquire specific functions related to recognition, selection, and acceptance of the allogeneic embryo, as well as to development of maternal immune tolerance. In this review we discuss the relationship between the decidualization of DSCs and pathological obstetrical and gynaecological conditions. Moreover, the critical influence of DSCs on local immune cells populations as well as their relationship to the onset and maintenance of immune tolerance is described.

  14. Survivin is a guardian of the intestinal stem cell niche and its expression is regulated by TGF-β.

    Science.gov (United States)

    Martini, Eva; Schneider, Evelyn; Neufert, Clemens; Neurath, Markus F; Becker, Christoph

    2016-11-01

    As an inhibitor of apoptosis (IAP) family member, Survivin is known for its role during regulation of apoptosis. More recently its function as a cell cycle regulator has become evident. Survivin was shown to play a pivotal role during embryonic development and is highly expressed in regenerative tissue as well as in many cancer types. We examined the function of Survivin during mouse intestinal organogenesis and in gut pathophysiology. We found high expression of Survivin in experimentally induced colon cancer in mice but also in colon tumors of humans. Moreover, Survivin was regulated by TGF-β and was found to be highly expressed during mucosal healing following intestinal inflammation. We identified that expression of Survivin is essential early on in life, as specific deletion of Survivin in Villin expressing cells led to embryonic death around day 12 post coitum. Together with our recent study on the role of Survivin in the gut of adult mice our data demonstrate that Survivin is an essential guardian of embryonic gut development and adult gut homeostasis protecting the epithelium from cell death promoting the proliferation of intestinal stem and progenitor cells.

  15. Cell Secretion: Current Structural and Biochemical Insights

    Directory of Open Access Journals (Sweden)

    Saurabh Trikha

    2010-01-01

    Full Text Available Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150nm in diameter in acinar cells of the exocrine pancreas to 12nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

  16. Current Progress with Primate Embryonic Stem Cells

    OpenAIRE

    Byrne, James A.; Mitalipov, Shoukhrat M.; Wolf, Don P

    2006-01-01

    Embryonic stem cells (ESCs) can proliferate indefinitely, maintain an undifferentiated pluripotent state and differentiate into any cell type. Differentiation of ESCs into various specific cell-types may be able to cure or alleviate the symptoms of various degenerative diseases. Unresolved issues regarding maintaining function, possible apoptosis and tumor formation in vivo mean a prudent approach should be taken towards advancing ESCs into human clinical trials. Rhesus macaques provide the i...

  17. Circumbinary Habitability Niches

    CERN Document Server

    Mason, Paul A; Cuartas-Restrepo, Pablo A; Clark, Joni M

    2014-01-01

    Binaries could provide the best niches for life in the galaxy. Though counterintuitive, this assertion follows directly from stellar tidal interaction theory and the evolution of lower mass stars. There is strong evidence that chromospheric activity of rapidly rotating young stars may be high enough to cause mass loss from atmospheres of potentially habitable planets. The removal of atmospheric water is most critical. Tidal breaking in binaries could help reduce magnetic dynamo action and thereby chromospheric activity in favor of life. We call this the Binary Habitability Mechanism (BHM), that we suggest allows for water retention at levels comparable to or better than Earth. We discuss novel advantages that life may exploit, in these cases, and suggest that life may even thrive on some circumbinary planets. We find that while many binaries do not benefit from BHM, high quality niches do exist for various combinations of stars between 0.55 and 1.0 solar masses. For a given pair of stellar masses, BHM operate...

  18. Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis

    Science.gov (United States)

    Balandrán, Juan Carlos; Purizaca, Jessica; Enciso, Jennifer; Dozal, David; Sandoval, Antonio; Jiménez-Hernández, Elva; Alemán-Lazarini, Leticia; Perez-Koldenkova, Vadim; Quintela-Núñez del Prado, Henry; Rios de los Ríos, Jussara; Mayani, Héctor; Ortiz-Navarrete, Vianney; Guzman, Monica L.; Pelayo, Rosana

    2017-01-01

    Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis. PMID:28111575

  19. Stem cells in neurology - current perspectives

    Directory of Open Access Journals (Sweden)

    Chary Ely Marquez Batista

    2014-06-01

    Full Text Available Central nervous system (CNS restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective : The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method : Literature review of animal and human clinical experimental trials, using the following key words: “stem cell”, “neurogenesis”, “Parkinson”, “Huntington”, “amyotrophic lateral sclerosis”, “traumatic brain injury”, “spinal cord injury”, “ischemic stroke”, and “demyelinating diseases”. Conclusion : Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.

  20. Effects of cisplatin on potassium currents in CT26 cells

    Directory of Open Access Journals (Sweden)

    Naveen Sharma

    2016-01-01

    Conclusion: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM. Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.

  1. Fuel cells: a survey of current developments

    Science.gov (United States)

    Cropper, Mark A. J.; Geiger, Stefan; Jollie, David M.

    Since the first practical uses of fuel cells were developed, it has become clear that they could find use in many products over a wide power range of milliwatts to tens of megawatts. Throughout the 1990s, and later, there has been significant work carried out on adapting the various different fuel cell technologies for use in targetted consumer and industrial applications. This paper discusses these developments and gives details on the specific market segments for providing power to vehicles, portable devices and large- and small-scale stationary power generation.

  2. The prostate cancer bone marrow niche: more than just ‘fertile soil’

    Institute of Scientific and Technical Information of China (English)

    Elisabeth A Pedersen; Yusuke Shiozawa; Kenneth J Pienta; Russell S Taichman

    2012-01-01

    The hematopoietic stem cell (HSC) niche in the bone marrow has been studied extensively over the past few decades,yet the bone marrow micmenvironment that supports the growth of metastatic prostate cancer (PCa) has only been recently considered to be a specialized ‘niche' as well.New evidence supports the fact that disseminated tumor cells (DTCs) of PCa actually target the HSC niche,displace the occupant HSCs and take up residence in the pre-existing niche space.This review describes some of the evidence and mechanisms by which DTCs act as molecular parasites of the HSC niche.Furthermore,the interactions between DTCs,HSCs and the niche may provide new targets for niche-directed therapy,as well as insight into the perplexing clinical manifestations of metastatic PCa disease.

  3. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

    Sorensen, M; Lassen, U; Hansen, H H

    1998-01-01

    This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...

  4. Protozoan grazing reduces the current output of microbial fuel cells.

    Science.gov (United States)

    Holmes, Dawn E; Nevin, Kelly P; Snoeyenbos-West, Oona L; Woodard, Trevor L; Strickland, Justin N; Lovley, Derek R

    2015-10-01

    Several experiments were conducted to determine whether protozoan grazing can reduce current output from sediment microbial fuel cells. When marine sediments were amended with eukaryotic inhibitors, the power output from the fuel cells increased 2-5-fold. Quantitative PCR showed that Geobacteraceae sequences were 120 times more abundant on anodes from treated fuel cells compared to untreated fuel cells, and that Spirotrichea sequences in untreated fuel cells were 200 times more abundant on anode surfaces than in the surrounding sediments. Defined studies with current-producing biofilms of Geobacter sulfurreducens and pure cultures of protozoa demonstrated that protozoa that were effective in consuming G. sulfurreducens reduced current production up to 91% when added to G. sulfurreducens fuel cells. These results suggest that anode biofilms are an attractive food source for protozoa and that protozoan grazing can be an important factor limiting the current output of sediment microbial fuel cells.

  5. Hürthle cell carcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Ahmadi S

    2016-11-01

    Full Text Available Sara Ahmadi,1 Michael Stang,2 Xiaoyin “Sara” Jiang,3 Julie Ann Sosa2,4,5 1Division of Endocrinology, Department of Medicine, 2Section of Endocrine Surgery, Department of Surgery, 3Department of Pathology, Duke University Medical Center, 4Duke Cancer Institute, 5Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA Abstract: Hürthle cell carcinoma (HCC can present either as a minimally invasive or as a widely invasive tumor. HCC generally has a more aggressive clinical behavior compared with the other differentiated thyroid cancers, and it is associated with a higher rate of distant metastases. Minimally invasive HCC demonstrates much less aggressive behavior; lesions <4 cm can be treated with thyroid lobectomy alone, and without radioactive iodine (RAI. HCC has been observed to be less iodine-avid compared with other differentiated thyroid cancers; however, recent data have demonstrated improved survival with RAI use in patients with HCC >2 cm and those with nodal and distant metastases. Patients with localized iodine-resistant disease who are not candidates for a wait-and-watch approach can be treated with localized therapies. Systemic therapy is reserved for patients with progressive, widely metastatic HCC. Keywords: thyroid cancer, thyroid nodule, follicular cell carcinoma, Hurthle cell lesion, minimally invasive HCC

  6. Membrane currents of spiking cells isolated from turtle retina.

    Science.gov (United States)

    Lasater, E M; Witkovsky, P

    1990-05-01

    We examined the membrane properties of spiking neurons isolated from the turtle (Pseudemys scripta) retina. The cells were maintained in culture for 1-7 days and were studied with the whole cell patch clamp technique. We utilized cells whose perikaryal diameters were greater than 15 microns since Kolb (1982) reported that ganglion cell perikarya in Pseudemys retina are 13-25 microns, whereas amacrine perikarya are less than 14 microns in diameter. We identified 5 currents in the studied cells: (1) a transient sodium current (INa) blocked by TTX, (2) a sustained calcium current (ICa) blocked by cobalt and enhanced by Bay-K 8644, (3) a calcium-dependent potassium current (IK(Ca)), (4) an A-type transient potassium current (IA) somewhat more sensitive to 4-AP than TEA, (5) a sustained potassium current (IK) more sensitive to TEA than 4-AP. The estimated average input resistance of the cells at -70 mV was 720 +/- 440 M omega. When all active currents were blocked, the membrane resistance between -130 and +20 mV was 2.5 G omega. When examined under current clamp, some cells produced multiple spikes to depolarizing steps of 0.1-0.3 nA, whereas other cells produced only a single spike irrespective of the strength of the current pulse. Most single spikers had an outward current that rose to a peak relatively slowly, whereas multiple spikers tend to have a more rapidly activating outward current. Under current clamp, 4-AP slowed the repolarization phase of the spike thus broadening it, but did not always abolish the ability to produce multiple spikes. TEA induced a depolarized plateau following the initial spike which precluded further spikes. It thus appears that the spiking patterns of the retinal cells are shaped primarily by the kinetics of INa, IK and IA and to a lesser extent by IK(Ca).

  7. In search of a temporal niche: environmental factors.

    Science.gov (United States)

    Hut, Roelof A; Kronfeld-Schor, Noga; van der Vinne, Vincent; De la Iglesia, Horacio

    2012-01-01

    Time as an ecological niche variable or "temporal niche" can be defined in the context of the most prominent environmental cycles, including the tidal cycle, the lunar day and month, the solar day, and the earth year. For the current review, we focus on the 24-h domain generated through the earth's rotation around its axis (solar day). The daily environmental cycles of light and temperature are a dominant ecological factor generating a variety of adaptations among animals. In this review, we describe these adaptations with a special focus on the visual system and on the adaptive plasticity of activity patterns. Our goals are: (1) Underscore the importance of the 24-h time axis as critical variable in the ecological niche. (2) Highlight cases of temporal niche switches at the evolutionary timescale (phylogenetic level). (3) Review temporal niche switching within an individual's lifespan. (4) Evaluate possible underlying mechanisms for temporal niche switching. (5) Describe a new hypothesis of circadian thermoenergetics which may explain several cases of temporal niche switching in mammals. With this, we hope to inspire experiments under natural conditions or more complex laboratory environments, aimed to reveal environmental factors and mechanisms underlying specific temporal programs.

  8. Mammalian niche conservation through deep time.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

  9. Current MR imaging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sae Lin; Sung, Seuk Jae [Dept. of Radiology, Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2016-08-15

    Renal cell carcinoma (RCC) consists of approximately 85-90% of renal masses, and its incidence is increasing due to widespread use of modern imaging modalities such as ultrasonography or computed tomography. Computed tomography has served an important role in the diagnosis and staging of RCC; however, recent advances in magnetic resonance imaging (MRI) techniques have considerably improved our ability to predict tumor biology beyond the morphologic assessment. Multiparametric MRI protocols include standard sequences tailored for the morphologic evaluation and acquisitions that provide information about the tumor microenvironment such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. The role of multiparametric MRI in the evaluation of RCC now extends to preoperative characterization of RCC subtypes, histologic grade, and quantitative assessment of tumor response to targeted therapies in patients with metastatic disease. Herein, the clinical applications and recent advances in MRI applied to RCC are reviewed along with its merits and demerits. We aimed to review MRI techniques and image analysis that can improve the management of patients with RCC. Familiarity with the advanced MRI techniques and various imaging findings of RCC would also facilitate optimal clinical recommendations for patients.

  10. Ultra-Low Voltage Class AB Switched Current Memory Cell

    DEFF Research Database (Denmark)

    Igor, Mucha

    1996-01-01

    This paper presents the theoretical basis for the design of class AB switched current memory cells employing floating-gate MOS transistors, suitable for ultra-low-voltage applications. To support the theoretical assumptions circuits based on these cells were designed using a CMOS process with thr......This paper presents the theoretical basis for the design of class AB switched current memory cells employing floating-gate MOS transistors, suitable for ultra-low-voltage applications. To support the theoretical assumptions circuits based on these cells were designed using a CMOS process...... with threshold voltages of 0.9V. Both hand calculations and PSPICE simulations showed that the cells designed allowed a maximum signal range better than +/-13 micoamp, with a supply voltage down to 1V and a quiescent bias current of 1 microamp, resulting in a very high current efficiency and effective power...

  11. The pitfalls of niche marketing.

    Science.gov (United States)

    Raynor, M E

    1992-01-01

    Corporate marketers have jumped on the micromarketing bandwagon, but many have discovered that the path to profits contains a number of potholes. This article details three companies' niche marketing mistakes; the author suggests how to avoid them.

  12. Current interruption measurement and analysis for PEM fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Sun, J.C.; Yuan, X.; Wang, H. [National Research Council of Canada, Vancouver, BC (Canada). Inst. for Fuel Cell Innovation

    2007-07-01

    The ohmic resistance, charge transfer resistance and the capacity discharge limit of proton exchange membrane (PEM) fuel cells can be evaluated and characterized by a newly developed, low cost, current interruption measuring method. This paper presented the results of a study in which the current interruption measurement for a PEM fuel cell was set up and proven through measurements with a dummy cell. The current interruption characteristics of a 500 W PEM fuel cell stack with an active area of 280 cm{sup 2} was measured using the National Instrument PCI data acquisition unit combined with a TDI electronics load-bank and a FuelCon test station, at different load currents. The ohmic loss of the stack determined by current interruption measurements was in good agreement with that determined by AC impedance spectroscopy. The same setup was shown to be effective for single cell measurements of a small PEM fuel cell and for a PEM fuel cell stack with a load bank. It was concluded that the current interruption measurement is much faster than the AC impedance method, but has lower accuracy, particularly for a signal with high noise. 1 ref., 10 figs.

  13. Current distribution within parallel-connected battery cells

    Science.gov (United States)

    Brand, Martin J.; Hofmann, Markus H.; Steinhardt, Marco; Schuster, Simon F.; Jossen, Andreas

    2016-12-01

    Parallel connections can be found in many battery applications. Therefore, it is of high interest to understand how the current distributes within parallel battery cells. However, the number of publications on this topic is comparably low. Furthermore, the measurement set-ups are often not clearly defined in existing publications and it is likely that additional impedances distorted the measured current distributions. In this work, the principles of current distributions within parallel-connected battery cells are investigated theoretically, with an equivalent electric circuit model, and by measurements. A measurement set-up is developed that does not significantly influence the measurements, as proven by impedance spectroscopy. On this basis, two parameter scenarios are analyzed: the ΔR scenario stands for battery cells with differing impedances but similar capacities and the ΔC scenario for differing capacities and similar impedances. Out of 172 brand-new lithium-ion battery cells, pairs are built to practically represent the ΔR and ΔC scenarios. If a charging pulse is applied to the ΔR scenario, currents initially divide according to the current divider but equalize in constant current phases. The current divider has no effect on ΔC pairs but, as a rule of thumb for long-term loads, currents divide according to the battery cell capacities.

  14. Interdigitated back contact solar cell with high-current collection

    Science.gov (United States)

    Garner, C. M.; Nasby, R. D.; Sexton, F. W.; Rodriguez, J. L.; Norwood, D. P.

    Internal current collection efficiencies greater than 90% and energy conversion efficiencies of 18 % at 30 suns were measured on a laboratory version of the interdigitated back contact (IBC) solar cell. A phosphorous gettering diffusion was performed on the front surface and then etched off to achieve these high current collection efficiencies. Thermal oxides were grown on the front and back of the cell to passivate the silicon surfaces. Although the internal collection efficiencies of the cell were high, series resistance caused the fill factor (FF) to decrease at concentrations above 30 suns. Dark current measurements on cells with a new grid spacing indicate that the series resistance is much lower than in the previous cell design. It is suggested that this should result in higher efficiencies at high concentration.

  15. Whole-cell recordings of calcium and potassium currents in acutely isolated smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Qing Cai; Zhong-Liang Zhu; Xiao-Li Fan

    2006-01-01

    AIM: To record calcium and potassium currents in acutely isolated smooth muscle cells of mesenteric arterial branches in rats.METHODS: Smooth muscle cells were freshly isolated by collagenase digest and mechanical trituration with polished pipettes. Patch clamp technique in whole-cell mode was employed to record calcium and potassium currents.RESULTS: The procedure dissociated smooth muscle cells without impairing the electrophysiological characteristics of the cells. The voltage-gated Ca2+ and potassium currents were successfully recorded using whole-cell patch clamp configuration.CONCLUSION: The method dissociates smooth muscle cells from rat mesenteric arterial branches. Voltage-gated channel currents can be recorded in this preparation.

  16. Improved analytical current voltage characteristics of a solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Yli-Koski, M.; Tuominen, E.; Acerbis, M.; Sinkkonen, J.

    1997-12-31

    Application of the Green`s function method to the calculation of the current voltage characteristics of a pn-junction solar cell makes possible to extract more reliable and exact information about the behavior of the cell. With this method not only the minority carrier diffusion currents but also the drift currents in quasi- neutral regions of the solar cell can be taken into consideration. Furthermore, this approach is not limited to an exponentially decaying minority carrier generation function but is valid for any type of optical generation. In addition, the injection boundary condition is exploited with the result that not only the pn-diode current but also the current resulting from the optical generation depends on the voltage of the solar cell. Applying the method also gives the so called position dependent collection efficiency function which is defined as the probability that an electron-hole pair created at a certain point inside the solar cell will contribute to the current leaving the cell. (orig.) 15 refs.

  17. Three-dimensional co-culture of mesenchymal stromal cells and differentiated osteoblasts on human bio-derived bone scaffolds supports active multi-lineage hematopoiesis in vitro: Functional implication of the biomimetic HSC niche

    Science.gov (United States)

    Huang, Xiaobing; Zhu, Biao; Wang, Xiaodong; Xiao, Rong; Wang, Chunsen

    2016-01-01

    Recent studies have indicated that the hematopoietic stem/progenitor cell (HSPC) niche, consisting of two major crucial components, namely osteoblasts (OBs) and mesenchymal stromal cells (MSCs), is responsible for the fate of HSPCs. Thus, closely mimicking the HSPC niche ex vivo may be an efficient strategy with which to develop new culture strategies to specifically regulate the balance between HSPC self-renewal and proliferation. The aim of this study was to establish a novel HSPC three-dimensional culture system by co-culturing bone marrow-derived MSCs and OBs differentiated from MSCs without any cytokines as feeder cells and applying bio-derived bone from human femoral metaphyseal portion as the scaffold. Scanning electron microscopy revealed the excellent biocompatibility of bio-derived bone with bone marrow-derived MSCs and OBs differentiated from MSCs. Western blot analysis revealed that many cytokines, which play key roles in HSPC regulation, were comprehensively secreted, while ELISA revealed that extracellular matrix molecules were also highly expressed. Hoechst 33342/propidium iodide fluorescence staining proved that our system could be used to supply a long-term culture of HSPCs. Flow cytometric analysis and qPCR of p21 expression demonstrated that our system significantly promoted the self-renewal and ex vivo expansion of HSPCs. Colony-forming unit (CFU) and long-term culture-initiating cell (LTC-IC) assays confirmed that our system has the ability for both the expansion of CD34+ hematopoietic stem cells (HPCs) and the maintenance of a primitive cell subpopulation of HSCs. The severe-combined immunodeficient mouse repopulating cell assay revealed the promoting effects of our system on the expansion of long-term primitive transplantable HSCs. In conclusion, our system may be a more comprehensive and balanced system which not only promotes the self-renewal and ex vivo expansion of HSPCs, but also maintains primitive HPCs with superior phenotypic and

  18. Intensity modulated short circuit current spectroscopy for solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Kavasoglu, Nese; Sertap Kavasoglu, A.; Birgi, Ozcan; Oktik, Sener [Mugla University, Faculty of Arts and Sciences, Physics Department, TR-48000 Mugla (Turkey); Mugla University Clean Energy Research and Development Centre, TR-48000 Mugla (Turkey)

    2011-02-15

    Understanding charge separation and transport is momentously important for the rectification of solar cell performance. To probe photo-generated carrier dynamics, we implemented intensity modulated short circuit current spectroscopy (IMSCCS) on porous Si and Cu(In{sub x},Ga{sub 1-x})Se{sub 2} solar cells. In this experiment, the solar cells were lightened with sinusoidally modulated monochromatic light. The photocurrent response of the solar cell as a function of modulation frequency is measured as the optoelectronic transfer function of the system. The optoelectronic transfer function introduces the connection between the modulated light intensity and measured AC current of the solar cell. In this study, interaction of free carriers with the density of states of the porous Si and Cu(In{sub x}, Ga{sub 1-x})Se{sub 2} solar cells was studied on the basis of charge transport time by IMSCCS data. (author)

  19. Introducing BioSARN - an ecological niche model refinement tool.

    Science.gov (United States)

    Heap, Marshall J

    2016-08-01

    Environmental niche modeling outputs a biological species' potential distribution. Further work is needed to arrive at a species' realized distribution. The Biological Species Approximate Realized Niche (BioSARN) application provides the ecological modeler with a toolset to refine Environmental niche models (ENMs). These tools include soil and land class filtering, niche area quantification and novelties like enhanced temporal corridor definition, and output to a high spatial resolution land class model. BioSARN is exemplified with a study on Fraser fir, a tree species with strong land class and edaphic correlations. Soil and land class filtering caused the potential distribution area to decline 17%. Enhanced temporal corridor definition permitted distinction of current, continuing, and future niches, and thus niche change and movement. Tile quantification analysis provided further corroboration of these trends. BioSARN does not substitute other established ENM methods. Rather, it allows the experimenter to work with their preferred ENM, refining it using their knowledge and experience. Output from lower spatial resolution ENMs to a high spatial resolution land class model is a pseudo high-resolution result. Still, it maybe the best that can be achieved until wide range high spatial resolution environmental data and accurate high precision species occurrence data become generally available.

  20. Current blocking and current collection in CIGSe solar cells depending on sodium content

    Energy Technology Data Exchange (ETDEWEB)

    Puttnins, Stefan; Daume, Felix [Solarion AG, Leipzig (Germany); Institut fuer Experimentelle Physik II, Universitaet Leipzig (Germany); Zachmann, Hendrik; Rahm, Andreas [Solarion AG, Leipzig (Germany); Grundmann, Marius [Institut fuer Experimentelle Physik II, Universitaet Leipzig (Germany)

    2010-07-01

    IV-curves of thin film solar cells often show non-idealites like voltage dependent carrier collection and current blocking behaviour. Sodium is long known to improve the efficiency of Cu(In,Ga)Se{sub 2} solar cells by increasing V{sub OC} and FF. However, the way in which sodium influences the electrical properties is still under discussion. We investigated the influence of sodium on voltage dependent carrier collection and current blocking behaviour. Losses caused by incomplete photocurrent collection can be reduced by increased sodium content in the CIGSe layer. Current blocking behaviour like the rollover effect is less pronounced with increased sodium content. The influences were analyzed both in detailed illumination intensity and temperature dependent IV-measurements as well as by extensive statistical analysis over thousands of produced flexible CIGSe solar cells. Theoretical models for this dependency were simulated with SCAPS-1D and show good agreement with respective measurements.

  1. Blood cell manufacture: current methods and future challenges.

    Science.gov (United States)

    Timmins, Nicholas E; Nielsen, Lars K

    2009-07-01

    Blood transfusion depends on availability of donor material, and concerns over supply and safety have spurred development of methods to manufacture blood from stem cells. Current methods could theoretically yield therapeutic doses of red blood cells (RBCs) and platelets. However, due to the very large number of cells required to have any impact on supply (currently 10(19) RBC/year in the US), realization of routine manufacture faces significant challenges. Current yields are orders of magnitude too low for production of meaningful quantities, and the physical scale of the problem is a challenge in itself. We discuss these challenges in relation to current methods and how it might be possible to realize limited 'blood pharming' of neutrophils in the near future.

  2. Current Stem Cell Delivery Methods for Myocardial Repair

    Directory of Open Access Journals (Sweden)

    Calvin C. Sheng

    2013-01-01

    Full Text Available Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs, the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs, mesenchymal stem cells (MSCs, and cardiac stem cells (CSCs. To engraft these cells into patients’ damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration.

  3. Corneal stem cells and tissue engineering: Current advancesand future perspectives

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Major advances are currently being made in regenerativemedicine for cornea. Stem cell-based therapiesrepresent a novel strategy that may substituteconventional corneal transplantation, albeit there aremany challenges ahead given the singularities of eachcellular layer of the cornea. This review recapitulatesthe current data on corneal epithelial stem cells,corneal stromal stem cells and corneal endothelialcell progenitors. Corneal limbal autografts containingepithelial stem cells have been transplanted in humansfor more than 20 years with great successful rates,and researchers now focus on ex vivo cultures andother cell lineages to transplant to the ocular surface.A small population of cells in the corneal endotheliumwas recently reported to have self-renewal capacity,although they do not proliferate in vivo . Two mainobstacles have hindered endothelial cell transplantationto date culture protocols and cell delivery methods tothe posterior cornea in vivo . Human corneal stromalstem cells have been identified shortly after therecognition of precursors of endothelial cells. Stromalstem cells may have the potential to provide a directcell-based therapeutic approach when injected tocorneal scars. Furthermore, they exhibit the ability todeposit organized connective tissue in vitro and maybe useful in corneal stroma engineering in the future.Recent advances and future perspectives in the field arediscussed.

  4. Current stem cell delivery methods for myocardial repair.

    Science.gov (United States)

    Sheng, Calvin C; Zhou, Li; Hao, Jijun

    2013-01-01

    Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration.

  5. Current progress and prospects of induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Induced pluripotent stem(iPS) cells are derived from somatic cells by ectopic expression of few transcription factors.Like embryonic stem(ES) cells,iPS cells are able to self-renew indefinitely and to differentiate into all types of cells in the body.iPS cells hold great promise for regenerative medicine,because iPS cells circumvent not only immunological rejection but also ethical issues.Since the first report on the derivation of iPS cells in 2006,many laboratories all over the world started research on iPS cells and have made significant progress.This paper reviews recent progress in iPS cell research,including the methods to generate iPS cells,the molecular mechanism of reprogramming in the formation of iPS cells,and the potential applications of iPS cells in cell replacement therapy.Current problems that need to be addressed and the prospects for iPS research are also discussed.

  6. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  7. Fibrocytes and the tissue niche in lung repair

    Directory of Open Access Journals (Sweden)

    Bjermer Leif

    2011-06-01

    Full Text Available Abstract Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.

  8. Re-examining "temporal niche".

    Science.gov (United States)

    Smarr, Benjamin L; Schwartz, Michael D; Wotus, Cheryl; de la Iglesia, Horacio O

    2013-07-01

    The circadian system temporally organizes physiology and behavior throughout the 24-h day. At the core of this organization lies a network of multiple circadian oscillators located within the central nervous system as well as in virtually every peripheral organ. These oscillators define a 24-h temporal landscape of mutually interacting circadian rhythms that is known as the temporal niche of a species. This temporal niche is constituted by the collective phases of all biological rhythms emerging from this multi-oscillatory system. We review evidence showing that under different environmental conditions, this system can adopt different harmonic configurations. Thus, the classic chronobiological approach of searching for "the" circadian phase of an animal-typically by studying circadian rhythms of locomotor activity-represents a narrow look into the circadian system of an animal. We propose that the study of hormonal rhythms may lead to a more insightful assessment of a species' temporal niche.

  9. Niche conservatism and the future potential range of Epipactis helleborine (Orchidaceae.

    Directory of Open Access Journals (Sweden)

    Marta Kolanowska

    Full Text Available The aim of the present study was to evaluate the current distribution of suitable niches for the invasive orchid species, Epipactis helleborine, and to estimate the possibility of its further expansion. Moreover, niche modeling tools were used to explain its rapid expansion in North America and to test the niche conservatism of the species. The maximum entropy method was used to create models of the suitable niche distribution. A database of E. helleborine localities was prepared based on the examination of herbarium specimens, information from electronic databases as well as data gathered during field works. The differences between the niches occupied by native and invasive populations were evaluated using the niche overlap and niche identity test indexes. Moreover, the coverage of the most suitable habitats for the species was measured for three future scenarios as well as for the present time model. Populations of E. helleborine occupy North American west coast habitats very similar to those preferred by native, Eurasian populations, while the expansion in the east coast is related to the niche shift. The created models of suitable niche distribution indicate that the species does not realize its potential niche in the native range. The total surface of the habitats potentially available for E. helleborine will decrease in all climate change scenarios created for 2080.

  10. Current focus of stem cell application in retinal repair

    Institute of Scientific and Technical Information of China (English)

    Maria L Alonso-Alonso; Girish Kumar Srivastava

    2015-01-01

    The relevance of retinal diseases, both in society'seconomy and in the quality of people's life who suffer withthem, has made stem cell therapy an interesting topic forresearch. Embryonic stem cells (ESCs), induced pluripotentstem cells (iPSCs) and adipose derived mesenchymal stemcells (ADMSCs) are the focus in current endeavors as asource of different retinal cells, such as photoreceptorsand retinal pigment epithelial cells. The aim is to applythem for cell replacement as an option for treating retinaldiseases which so far are untreatable in their advancedstage. ESCs, despite the great potential for differentiation,have the dangerous risk of teratoma formation as wellas ethical issues, which must be resolved before startinga clinical trial. iPSCs, like ESCs, are able to differentiatein to several types of retinal cells. However, the processto get them for personalized cell therapy has a high costin terms of time and money. Researchers are working toresolve this since iPSCs seem to be a realistic option fortreating retinal diseases. ADMSCs have the advantagethat the procedures to obtain them are easier. Despiteadvancements in stem cell application, there are stillseveral challenges that need to be overcome beforetransferring the research results to clinical application.This paper reviews recent research achievements of theapplications of these three types of stem cells as well asclinical trials currently based on them.

  11. Ecological niche of plant pathogens

    Directory of Open Access Journals (Sweden)

    Ecaterina Fodor

    2011-02-01

    Full Text Available Disease ecology is a new approach to the understanding of the spread and dynamics of pathogens in natural and man-made environments. Defining and describing the ecological niche of the pathogens is one of the major tasks for ecological theory, as well as for practitioners preoccupied with the control and forecasting of established and emerging diseases. Niche theory has been periodically revised, not including in an explicit way the pathogens. However, many progresses have been achieved in niche modeling of disease spread, but few attempts were made to construct a theoretical frame for the ecological niche of pathogens. The paper is a review of the knowledge accumulated during last decades in the niche theory of pathogens and proposes an ecological approach in research. It quest for new control methods in what concerns forest plant pathogens, with a special emphasis on fungi like organisms of the genus Phytophthora. Species of Phytophthora are the most successful plant pathogens of the moment, affecting forest and agricultural systems worldwide, many of them being invasive alien organisms in many ecosystems. The hyperspace of their ecological niche is defined by hosts, environment and human interference, as main axes. To select most important variables within the hyperspace, is important for the understanding of the complex role of pathogens in the ecosystems as well as for control programs. Biotic relationships within ecosystem of host-pathogen couple are depicted by ecological network and specific metrics attached to this. The star shaped network is characterized by few high degree nodes, by short path lengths and relatively low connectivity, premises for a rapid disturbance spread.

  12. Current progress and prospects of induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    CHEN LingYi; Liu Lin

    2009-01-01

    Induced pluripotent stem (iPS) cells are derived from somatic cells by ectopic expression of few transcription factors. Like embryonic stem (ES) cells, iPS cells are able to self-renew indefinitely and to differentiate into all types of cells in the body. iPS cells hold great promise for regenerative medicine,because iPS ceils circumvent not only immunological rejection but also ethical issues. Since the first report on the derivation of iPS cells in 2006, many laboratories all over the world started research on iPS cells and have made significant progress. This paper reviews recent progress in iPS cell research,Including the methods to generate iPS cells, the molecular mechanism of reprogramming in the formation of iPS ceils, and the potential applications of iPS cells in cell replacement therapy. Current problems that need to be addressed and the prospects for iPS research are also discussed.

  13. Concise Review: Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology

    Science.gov (United States)

    Park, DoYeun; Lim, Jaeho; Park, Joong Yull

    2015-01-01

    Stem cells have huge potential in many therapeutic areas. With conventional cell culture methods, however, it is difficult to achieve in vivo-like microenvironments in which a number of well-controlled stimuli are provided for growing highly sensitive stem cells. In contrast, microtechnology-based platforms offer advantages of high precision, controllability, scalability, and reproducibility, enabling imitation of the complex physiological context of in vivo. This capability may fill the gap between the present knowledge about stem cells and that required for clinical stem cell-based therapies. We reviewed the various types of microplatforms on which stem cell microenvironments are mimicked. We have assigned the various microplatforms to four categories based on their practical uses to assist stem cell biologists in using them for research. In particular, many examples are given of microplatforms used for the production of embryoid bodies and aggregates of stem cells in vitro. We also categorized microplatforms based on the types of factors controlling the behaviors of stem cells. Finally, we outline possible future directions for microplatform-based stem cell research, such as research leading to the production of well-defined environments for stem cells to be used in scaled-up systems or organs-on-a-chip, the regulation of induced pluripotent stem cells, and the study of the genetic states of stem cells on microplatforms. Significance Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment; therefore, systematic analysis and discrimination of the extracellular signals and intracellular pathways controlling the fate of cells and experimental realization of sensitive and controllable niche environments are critical. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently

  14. Is sodium current present in human sinoatrial node cells?

    Directory of Open Access Journals (Sweden)

    Arie O. Verkerk, Ronald Wilders, Marcel M.G.J. van Borren, Hanno L. Tan

    2009-01-01

    Full Text Available Pacemaker activity of the sinoatrial node has been studied extensively in various animal species, but is virtually unexplored in man. As such, it is unknown whether the fast sodium current (INa plays a role in the pacemaker activity of the human sinoatrial node. Recently, we had the unique opportunity to perform patch-clamp experiments on single pacemaker cells isolated from a human sinoatrial node. In 2 out of the 3 cells measured, we observed large inward currents with characteristics of INa. Although we were unable to analyze the current in detail, our findings provide strong evidence that INa is present in human sinoatrial node pacemaker cells, and that this INa is functionally available at potentials negative to -60 mV.

  15. Erythroblastic Islands: Specialized Mircoenvironmental Niches forErythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Chasis, Joel Anne

    2006-01-06

    This review focuses on current understanding of molecular mechanisms operating within erythroblastic islands including cell-cell adhesion, regulatory feedback, and central macrophage function. RECENT FINDINGS: Erythroblasts express a variety of adhesion molecules and recently two interactions have been identified that appear to be critical for island integrity. Erythroblast macrophage protein, expressed on erythroblasts and macrophages, mediates cell-cell attachments via homophilic binding. Erythroblast intercellular adhesion molecule-4 links erythroblasts to macrophages through interaction with macrophage alphav integrin. In intercellular adhesion molecule-4 knockout mice, erythroblastic islands are markedly reduced, whereas the erythroblast macrophage protein null phenotype is severely anemic and embryonic lethal. Retinoblastoma tumor suppressor (Rb) protein stimulates macrophage differentiation by counteracting inhibition of Id2 on PU.1, a transcription factor that is a crucial regulator of macrophage differentiation. Rb-deficient macrophages do not bind Rb null erythroblasts and the Rb null phenotype is anemic and embryonic lethal. Lastly, extruded nuclei rapidly expose phosphatidylserine on their surface, providing a recognition signal similar to apoptotic cells. SUMMARY: Although understanding of molecular mechanisms operating within islands is at an early stage, tantalizing evidence suggests that erythroblastic islands are specialized niches where intercellular interactions in concert with cytokines play critical roles in regulating erythropoiesis.

  16. Nicotine inhibits potassium currents in Aplysia bag cell neurons.

    Science.gov (United States)

    White, Sean H; Sturgeon, Raymond M; Magoski, Neil S

    2016-06-01

    Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K(+) with Cs(+) Consistent with an underlying mechanism of direct inhibition of one or more K(+) channels, nicotine was found to rapidly reduce the fast-inactivating A-type K(+) current as well as both components of the delayed-rectifier K(+) current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K(+) channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time.

  17. Solid Oxide Electrolysis Cells: Degradation at High Current Densities

    DEFF Research Database (Denmark)

    Knibbe, Ruth; Traulsen, Marie Lund; Hauch, Anne;

    2010-01-01

    The degradation of Ni/yttria-stabilized zirconia (YSZ)-based solid oxide electrolysis cells operated at high current densities was studied. The degradation was examined at 850°C, at current densities of −1.0, −1.5, and −2.0 A/cm2, with a 50:50 (H2O:H2) gas supplied to the Ni/YSZ hydrogen electrode...

  18. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    Directory of Open Access Journals (Sweden)

    Tony DeFalco

    2015-08-01

    Full Text Available The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs. Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1 and enzymes involved in retinoic acid (RA biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  19. The bone marrow endosteal niche: how far from the surface?

    Science.gov (United States)

    Cordeiro-Spinetti, Eric; Taichman, Russell S; Balduino, Alex

    2015-01-01

    Hematopoietic stem cells (HSC) self-renewal takes place in the same microenvironment in which massive hematopoietic progenitor proliferation, commitment, and differentiation will occur. This is only made possible if the bone marrow microenvironment comprises different specific niches, composed by different stromal cells that work in harmony to regulate all the steps of the hematopoiesis cascade. Histological and functional assays indicated that HSC and multipotent progenitors preferentially colonize the endosteal and subendosteal regions, in close association with the bone surface. Conversely, committed progenitors and differentiated cells are distributed in the central and perisinusoidal regions, respectively. Over the last decade, many investigative teams sought to define which cell types regulate the HSC niche, how they are organized, and to what extent they interface with each other. System dynamics requires different stromal cells to operate distinct functions over similar HSC pools rather than a single stromal cell type controlling everything. Therefore, our focus herein is to depict the players in the endosteal and subendosteal regions, named the endosteal niche, a necessary step to better understand the interactions of the HSC within the niche and to identify potential targets to manipulate and/or modulate normal and malignant HSC behavior.

  20. A niche role for cancer exosomes in metastasis.

    Science.gov (United States)

    Zhang, Yun; Wang, Xiao-Fan

    2015-06-01

    Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-derived factors by liver Kupffer cells and hepatic stellate cell activation to generate a fibrotic microenvironment with immune cell infiltrates that favours metastasis.

  1. A new Zero-Current-Transition PWM switching cell

    Energy Technology Data Exchange (ETDEWEB)

    Grigore, V. [Electronics and Telecommunications Faculty, `Politechnica` University Bucharest (Romania); Kyyrae, J. [Helsinki University of Technology, Otaniemi (Finland): Institute of Intelligent Power Electronics

    1997-12-31

    In this paper a new Zero-Current-Transition (ZCT) PWM switching cell is presented. The proposed switching cell is composed of the normal hard-switched PWM cell (consisting of one active switch and one passive switch), plus as auxiliary circuit. The auxiliary circuit is inactive during the ON ad OFF intervals of the switches in the normal PWM switch. The transitions between the two states are controlled by the auxiliary circuit. Prior to turn-off, the current through the active switch in the PWM cell is forced to zero, thus the turn-off losses of the active switch are practically eliminated. At turn-on the auxiliary circuit slows down the growing rate of the current through the main switch. Thus, turn-on losses are also very much reduced. The active switch operates under ZCT conditions, the passive switch (diode) has a controlled reverse recovery, while the switch in the auxiliary circuit operates under Zero-Current-Switching (ZCS) conditions. (orig.) 3 refs.

  2. Current view of mesenchymal stem cells biology (brief review

    Directory of Open Access Journals (Sweden)

    Maslova O. A.

    2012-06-01

    Full Text Available Although mesenchymal stem cells (MSC are in a focus of attention, some aspects of their biology are still unclear. This paper is a review of current research on MSC biology. The use of MSC in regenerative medicine is also briefly discussed.

  3. Interdigitated back contact solar cell with high-current collection

    Energy Technology Data Exchange (ETDEWEB)

    Garner, C. M.; Nasby, R. D.; Sexton, F. W.; Rodriguez, J. L.; Norwood, D. P.

    1981-01-01

    Internal current-collection efficiencies greater than 90 percent and energy-conversion efficiencies of 18 percent at 30 suns have been measured on a laboratory version of the interdigitated back contact (IBC) solar cell. The quantum efficiency at 600 nm was greater than 90 percent which implies a minority carrier lifetime of greater than 350 ..mu..sec and a front surface recombination velocity of less than 30 cm/sec on the better devices. To achieve these high-current collection efficiencies, a phosphorous gettering diffusion was performed on the front surface and then etched off. Also, thermal oxides were grown on the front and back of the cell to passivate the silicon surfaces. Although the internal collection efficiencies of the cell were high, series resistance caused the fill factor (FF) to decrease at concentrations above 30 suns. Dark current measurements on cells with a new grid spacing indicate that the series resistance is much lower than in the previous cell design. This should result in higher efficiencies at high concentration.

  4. A perisinusoidal niche for extramedullary haematopoiesis in the spleen

    Science.gov (United States)

    Acar, Melih; Murphy, Malea M.; Richardson, James; Zhao, Zhiyu; Morrison, Sean J.

    2015-01-01

    Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here, we assessed the sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses. PMID:26570997

  5. A perisinusoidal niche for extramedullary haematopoiesis in the spleen.

    Science.gov (United States)

    Inra, Christopher N; Zhou, Bo O; Acar, Melih; Murphy, Malea M; Richardson, James; Zhao, Zhiyu; Morrison, Sean J

    2015-11-26

    Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.

  6. Breast cancer stem cells: current advances and clinical implications.

    Science.gov (United States)

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S

    2015-01-01

    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  7. Three-dimensional co-culture of mesenchymal stromal cells and differentiated osteoblasts on human bio-derived bone scaffolds supports active multi-lineage hematopoiesis in vitro: Functional implication of the biomimetic HSC niche.

    Science.gov (United States)

    Huang, Xiaobing; Zhu, Biao; Wang, Xiaodong; Xiao, Rong; Wang, Chunsen

    2016-10-01

    Recent studies have indicated that the hematopoietic stem/progenitor cell (HSPC) niche, consisting of two major crucial components, namely osteoblasts (OBs) and mesenchymal stromal cells (MSCs), is responsible for the fate of HSPCs. Thus, closely mimicking the HSPC niche ex vivo may be an efficient strategy with which to develop new culture strategies to specifically regulate the balance between HSPC self-renewal and proliferation. The aim of this study was to establish a novel HSPC three-dimensional culture system by co-culturing bone marrow-derived MSCs and OBs differentiated from MSCs without any cytokines as feeder cells and applying bio-derived bone from human femoral metaphyseal portion as the scaffold. Scanning electron microscopy revealed the excellent biocompatibility of bio-derived bone with bone marrow-derived MSCs and OBs differentiated from MSCs. Western blot analysis revealed that many cytokines, which play key roles in HSPC regulation, were comprehensively secreted, while ELISA revealed that extracellular matrix molecules were also highly expressed. Hoechst 33342/propidium iodide fluorescence staining proved that our system could be used to supply a long-term culture of HSPCs. Flow cytometric analysis and qPCR of p21 expression demonstrated that our system significantly promoted the self-renewal and ex vivo expansion of HSPCs. Colony-forming unit (CFU) and long-term culture-initiating cell (LTC-IC) assays confirmed that our system has the ability for both the expansion of CD34+ hematopoietic stem cells (HPCs) and the maintenance of a primitive cell subpopulation of HSCs. The severe-combined immunodeficient mouse repopulating cell assay revealed the promoting effects of our system on the expansion of long-term primitive transplantable HSCs. In conclusion, our system may be a more comprehensive and balanced system which not only promotes the self-renewal and ex vivo expansion of HSPCs, but also maintains primitive HPCs with superior

  8. Cell therapy for liver diseases: current medicine and future promises.

    Science.gov (United States)

    Alejandra, Meza-Ríos; Juan, Armendáriz-Borunda; Ana, Sandoval-Rodríguez

    2015-06-01

    Liver diseases are a major health problem worldwide since they usually represent the main causes of death in most countries, causing excessive costs to public health systems. Nowadays, there are no efficient current therapies for most hepatic diseases and liver transplant is infrequent due to the availability of organs, cost and risk of transplant rejection. Therefore, alternative therapies for liver diseases have been developed, including cell-based therapies. Stem cells (SCs) are characterized by their self-renewing capacity, unlimited proliferation and differentiation under certain conditions into tissue- or organ-specific cells with special functions. Cell-based therapies for liver diseases have been successful in experimental models, showing anti-inflammatory, antifibrogenic and regenerative effects. Nowadays, clinical trials using SCs for liver pathologies are increasing in number, and those that have reached publication have achieved favorable effects, encouraging us to think that SCs will have a potential clinical use in a short time.

  9. Structural ECM components in the premetastatic and metastatic niche

    DEFF Research Database (Denmark)

    Høye, Anette M; Erler, Janine T

    2016-01-01

    The aim of this review is to give an overview of the extracellular matrix (ECM) components that are important for creating structural changes in the premetastatic and metastatic niche. The successful arrival and survival of cancer cells that have left the primary tumor and colonized distant sites...

  10. Current Collecting Grids for ITO-Free Solar Cells

    DEFF Research Database (Denmark)

    Galagan, Yulia; Zimmermann, Birger; Coenen, Erica W. C.

    2012-01-01

    Indium-tin-oxide (ITO) free polymer solar cells prepared by ink jet printing a composite front electrode comprising silver grid lines and a semitransparent PEDOT:PSS conductor are demonstrated. The effect of grid line density is explored for a large series of devices and a careful modeling study...... enabling the identification of the most rational grid structure is presented. Both optical and light beam induced current (LBIC) mapping of the devices are used to support the power loss model and to follow the evolution of the performance over time. Current generation is found to be evenly distributed...

  11. Maximum Entropy-Based Ecological Niche Model and Bio-Climatic Determinants of Lone Star Tick (Amblyomma americanum) Niche.

    Science.gov (United States)

    Raghavan, Ram K; Goodin, Douglas G; Hanzlicek, Gregg A; Zolnerowich, Gregory; Dryden, Michael W; Anderson, Gary A; Ganta, Roman R

    2016-03-01

    The potential distribution of Amblyomma americanum ticks in Kansas was modeled using maximum entropy (MaxEnt) approaches based on museum and field-collected species occurrence data. Various bioclimatic variables were used in the model as potentially influential factors affecting the A. americanum niche. Following reduction of dimensionality among predictor variables using principal components analysis, which revealed that the first two principal axes explain over 87% of the variance, the model indicated that suitable conditions for this medically important tick species cover a larger area in Kansas than currently believed. Soil moisture, temperature, and precipitation were highly correlated with the first two principal components and were influential factors in the A. americanum ecological niche. Assuming that the niche estimated in this study covers the occupied distribution, which needs to be further confirmed by systematic surveys, human exposure to this known disease vector may be considerably under-appreciated in the state.

  12. Influence of in vitro biomimicked stem cell 'niche' for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontaneous stem cell transformation enhanced by the matrix environment.

    Science.gov (United States)

    Kim, Jae Hyung; Shin, Sang-Hyun; Li, Tian Zhu; Suh, Hwal

    2016-01-01

    Niche appears important for preventing the spontaneous differentiation or senescence that cells undergo during in vitro expansion. In the present study, it was revealed that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) undergo senescence-related differentiation into the myocardial lineage in vitro without any induction treatment. This phenomenon occurred over the whole population of MCSs, much different from conventional differentiation with limited frequency of occurrence, and was accompanied by a change of morphology into large, flat cells with impeded proliferation, which are the representative indications of MSC senescence. By culturing MSCs under several culture conditions, it was determined that induction treatment with 5-azacytidine was not associated with the phenomenon, but the serum-starvation condition, under which proliferation is severely hampered, caused senescence progression and upregulation of cardiac markers. Nevertheless, MSCs gradually developed a myocardial phenotype under normal culture conditions over a prolonged culture period and heterogeneous populations were formed. In perspectives of clinical applications, this must be prevented for fair and consistent outcomes. Hence, the biomimetic 'niche' was constituted for hBM-MSCs by cultivating on a conventionally available extracellular matrix (ECM). Consequently, cells on ECM regained a spindle-shape morphology, increased in proliferation rate by two-fold and showed decreased expression of cardiac markers at both the mRNA and protein levels. In conclusion, the outcome indicates that progression of MSC senescence may occur via myocardial differentiation during in vitro polystyrene culture, and this can be overcome by employing appropriate ECM culture techniques.

  13. Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Baldur Kristjánsson

    2014-01-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease most commonly occurring in the ageing population. It is a slow progressive condition resulting in the destruction of hyaline cartilage followed by pain and reduced activity. Conventional treatments have little effects on the progression of the condition often leaving surgery as the last option. In the last 10 years tissue engineering utilising mesenchymal stem cells has been emerging as an alternative method for treating OA. Mesenchymal stem cells (MSCs are multipotent progenitor cells found in various tissues, most commonly bone marrow and adipose tissue. MSCs are capable of differentiating into osteocytes, adipocytes, and chondrocytes. Autologous MSCs can be easily harvested and applied in treatment, but allogenic cells can also be employed. The early uses of MSCs focused on the implantations of cell rich matrixes during open surgeries, resulting in the formation of hyaline-like durable cartilage. More recently, the focus has completely shifted towards direct intra-articular injections where a great number of cells are suspended and injected into affected joints. In this review the history and early uses of MSCs in cartilage regeneration are reviewed and different approaches in current trends are explained and evaluated.

  14. Phylogenetic conservatism of environmental niches in mammals.

    Science.gov (United States)

    Cooper, Natalie; Freckleton, Rob P; Jetz, Walter

    2011-08-01

    Phylogenetic niche conservatism is the pattern where close relatives occupy similar niches, whereas distant relatives are more dissimilar. We suggest that niche conservatism will vary across clades in relation to their characteristics. Specifically, we investigate how conservatism of environmental niches varies among mammals according to their latitude, range size, body size and specialization. We use the Brownian rate parameter, σ(2), to measure the rate of evolution in key variables related to the ecological niche and define the more conserved group as the one with the slower rate of evolution. We find that tropical, small-ranged and specialized mammals have more conserved thermal niches than temperate, large-ranged or generalized mammals. Partitioning niche conservatism into its spatial and phylogenetic components, we find that spatial effects on niche variables are generally greater than phylogenetic effects. This suggests that recent evolution and dispersal have more influence on species' niches than more distant evolutionary events. These results have implications for our understanding of the role of niche conservatism in species richness patterns and for gauging the potential for species to adapt to global change.

  15. p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

    Directory of Open Access Journals (Sweden)

    Kyung Hee Chang

    2014-12-01

    Full Text Available In the bone marrow (BM, hematopoietic progenitors (HPs reside in specific anatomical niches near osteoblasts (Obs, macrophages (MΦs, and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling. Consequently, Ob p62-deficient mice lose bone, Ob Ccl4 expression, and HP chemotaxis toward Cxcl12, resulting in egress of short-term hematopoietic stem cells and myeloid progenitors. Finally, Ccl4 expression and myeloid progenitor egress are reversed by deficiency of the p62 PB1-binding partner Nbr1. A functional “MΦ-Ob niche” is required for myeloid progenitor/short-term stem cell retention, in which Ob p62 is required to maintain NF-κB signaling repression, osteogenesis, and BM progenitor retention.

  16. Current Developments in Prokaryotic Single Cell Whole Genome Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Goudeau, Danielle; Nath, Nandita; Ciobanu, Doina; Cheng, Jan-Fang; Malmstrom, Rex

    2014-03-14

    Our approach to prokaryotic single-cell Whole Genome Amplification at the JGI continues to evolve. To increase both the quality and number of single-cell genomes produced, we explore all aspects of the process from cell sorting to sequencing. For example, we now utilize specialized reagents, acoustic liquid handling, and reduced reaction volumes eliminate non-target DNA contamination in WGA reactions. More specifically, we use a cleaner commercial WGA kit from Qiagen that employs a UV decontamination procedure initially developed at the JGI, and we use the Labcyte Echo for tip-less liquid transfer to set up 2uL reactions. Acoustic liquid handling also dramatically reduces reagent costs. In addition, we are exploring new cell lysis methods including treatment with Proteinase K, lysozyme, and other detergents, in order to complement standard alkaline lysis and allow for more efficient disruption of a wider range of cells. Incomplete lysis represents a major hurdle for WGA on some environmental samples, especially rhizosphere, peatland, and other soils. Finding effective lysis strategies that are also compatible with WGA is challenging, and we are currently assessing the impact of various strategies on genome recovery.

  17. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  18. Developmental cues and persistent neurogenic potential within an in vitro neural niche

    Directory of Open Access Journals (Sweden)

    Fairchild Corinne L

    2010-01-01

    Full Text Available Abstract Background Neurogenesis, the production of neural cell-types from neural stem cells (NSCs, occurs during development as well as within select regions of the adult brain. NSCs in the adult subependymal zone (SEZ exist in a well-categorized niche microenvironment established by surrounding cells and their molecular products. The components of this niche maintain the NSCs and their definitive properties, including the ability to self-renew and multipotency (neuronal and glial differentiation. Results We describe a model in vitro NSC niche, derived from embryonic stem cells, that produces many of the cells and products of the developing subventricular zone (SVZ and adult SEZ NSC niche. We demonstrate a possible role for apoptosis and for components of the extracellular matrix in the maintenance of the NSC population within our niche cultures. We characterize expression of genes relevant to NSC self-renewal and the process of neurogenesis and compare these findings to gene expression produced by an established neural-induction protocol employing retinoic acid. Conclusions The in vitro NSC niche shows an identity that is distinct from the neurally induced embryonic cells that were used to derive it. Molecular and cellular components found in our in vitro NSC niche include NSCs, neural progeny, and ECM components and their receptors. Establishment of the in vitro NSC niche occurs in conjunction with apoptosis. Applications of this culture system range from studies of signaling events fundamental to niche formation and maintenance as well as development of unique NSC transplant platforms to treat disease or injury.

  19. Mesenchymal stem cell therapy for osteoarthritis: current perspectives.

    Science.gov (United States)

    Wyles, Cody C; Houdek, Matthew T; Behfar, Atta; Sierra, Rafael J

    2015-01-01

    Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

  20. Spatial distributions of niche-constructing populations

    Directory of Open Access Journals (Sweden)

    Xiaozhuo Han

    2015-12-01

    Full Text Available Niche construction theory regards organisms not only as the object of natural selection but also an active subject that can change their own selective pressure through eco-evolutionary feedbacks. Through reviewing the existing works on the theoretical models of niche construction, here we present the progress made on how niche construction influences genetic structure of spatially structured populations and the spatial-temporal dynamics of metapopulations, with special focuses on mathematical models and simulation methods. The majority of results confirmed that niche construction can significantly alter the evolutionary trajectories of structured populations. Organism-environmental interactions induced by niche construction can have profound influence on the dynamics, competition and diversity of metapopulations. It can affect fine-scale spatially distribution of species and spatial heterogeneity of the environment. We further propose a few research directions with potentials, such as applying adaptive dynamics or spatial game theory to explore the effect of niche construction on phenotypic evolution and diversification.

  1. Current collecting grids for ITO-free solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Galagan, Yulia; Gorter, Harrie; Sabik, Sami; Andriessen, Ronn [Holst Centre, High Tech Campus 31, Eindhoven (Netherlands); Zimmermann, Birger [Fraunhofer Institute for Solar Energy Systems ISE, Freiburg (Germany); Coenen, Erica W.C. [TNO Technical Sciences, Eindhoven (Netherlands); Joergensen, Mikkel; Krebs, Frederik C. [Risoe National Laboratory for Sustainable Energy, Technical University of Denmark, Roskilde (Denmark); Tanenbaum, David M. [Risoe National Laboratory for Sustainable Energy, Technical University of Denmark, Roskilde (Denmark); Department of Physics and Astronomy, Pomona College, Claremont, CA (United States); Slooff, Lenneke H.; Veenstra, Sjoerd C.; Kroon, Jan M. [Energy Research Centre of the Netherlands (ECN), Petten (Netherlands)

    2012-01-15

    Indium-tin-oxide (ITO) free polymer solar cells prepared by ink jet printing a composite front electrode comprising silver grid lines and a semitransparent PEDOT:PSS conductor are demonstrated. The effect of grid line density is explored for a large series of devices and a careful modeling study enabling the identification of the most rational grid structure is presented. Both optical and light beam induced current (LBIC) mapping of the devices are used to support the power loss model and to follow the evolution of the performance over time. Current generation is found to be evenly distributed over the active area initially progressing to a larger graduation in areas with different performance. Over time coating defects also become much more apparent in the LBIC images. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties.

    Directory of Open Access Journals (Sweden)

    Pegah Ghiabi

    Full Text Available Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.

  3. Current and emerging treatment options for hairy cell leukemia

    Directory of Open Access Journals (Sweden)

    López-Rubio M

    2015-08-01

    Full Text Available Montserrat López-Rubio,1 Jose Antonio Garcia-Marco2 1Department of Hematology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, 2Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain Abstract: Hairy cell leukemia (HCL is a lymphoproliferative B-cell disorder characterized by pancytopenia, splenomegaly, and characteristic cytoplasmic hairy projections. Precise diagnosis is essential in order to differentiate classic forms from HCL variants, such as the HCL-variant and VH4-34 molecular variant, which are more resistant to available treatments. The current standard of care is treatment with purine analogs (PAs, such as cladribine or pentostatin, which provide a high rate of long-lasting clinical remissions. Nevertheless, ~30%–40% of the patients relapse, and moreover, some of these are difficult-to-treat refractory cases. The use of the monoclonal antibody rituximab in combination with PA appears to produce even higher responses, and it is often employed to minimize or eliminate residual disease. Currently, research in the field of HCL is focused on identifying novel therapeutic targets and potential agents that are safe and can universally cure the disease. The discovery of the BRAF mutation and progress in understanding the biology of the disease has enabled the scientific community to explore new therapeutic targets. Ongoing clinical trials are assessing various treatment strategies such as the combination of PA and anti-CD20 monoclonal antibodies, recombinant immunotoxins targeting CD22, BRAF inhibitors, and B-cell receptor signal inhibitors. Keywords: hairy cell leukemia, purine analogs, rituximab, immunotoxins, vemurafenib, ibrutinib

  4. Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae)

    Science.gov (United States)

    Gómez, Camila; Tenorio, Elkin A.; Montoya, Paola; Cadena, Carlos Daniel

    2016-01-01

    Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour. PMID:26865303

  5. Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae).

    Science.gov (United States)

    Gómez, Camila; Tenorio, Elkin A; Montoya, Paola; Cadena, Carlos Daniel

    2016-02-10

    Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour.

  6. Study on Molecular Mechanisms of Anti-proliferation and Metastasis of Yiqi Bushen Formula by Regulating the Gastric Cancer Stem Cell Niche and Notch Signaling Pathway%益气补肾方调控胃癌干细胞 niche 及Notch 信号通路抗转移分子机制研究

    Institute of Scientific and Technical Information of China (English)

    刘云霞; 徐叶峰; 蒋沈君; 姚勇伟; 王娜

    2016-01-01

    [目的]探讨益气补肾方调控胃癌肿瘤干细胞(cancer stem cells, CSC)niche 及 Notch 信号通路抗胃癌增殖转移的分子机制,为临床应用提供实验依据。[方法]采用人胃癌细胞株 NCI-N87建立胃癌 CSC 富集裸鼠荷瘤模型。裸鼠随机分为阴性对照组、模型对照组、氟尿嘧啶组(5-Fu 组)、益气补肾方组(益气补肾组)及益气补肾方+氟尿嘧啶组(协同组)。每组药物干预6周,观察裸鼠体质量变化及瘤体生长情况,比较各组肿瘤增殖及远处转移情况;采用 ELISA 法检测瘤体血管内皮生长因子受体-1(vascular endothelial growth factor receptor-1, VEGFR-1)、骨桥蛋白(osteopontin, OPN)、缺氧诱导因子-1α(hypoxia-inducible factor-1α, HIF-1α)、CXC 趋化因子受体4(CXC chemokine receptor 4, CXCR4)表达;采用免疫组化法检测肿瘤组织中 CD24、CD44、上皮细胞粘附分子(epithelial cell adhesion molecule,EpCAM)的表达;采用 Western blot 检测肿瘤组织 Notch1、Jagged1蛋白表达。[结果]给药6周后,益气补肾组、协同组及阴性对照组裸鼠体质量均明显重于模型对照组、5-Fu 组,差异均有统计学意义(P<0.01);模型对照组与阴性对照组裸鼠的瘤体均重于5-Fu 组、益气补肾组及协同组,差异有统计学意义(P<0.01)。5-Fu 组、益气补肾组及协同组裸鼠的肝脏、腹壁、淋巴结及肺的总转移率明显少于模型对照组,差异有统计学意义(P<0.05)。与模型对照组比,5-Fu 组、益气补肾组及协同组瘤体内 VEGFR-1、OPN、HIF-1α、CXCR4的表达下调,差异有统计学意义(P<0.05,P<0.01)。益气补肾组与协同组 CD24、CD44的表达均低于模型对照组及5-Fu 组,差异有统计学意义(P<0.05)。益气补肾组 EpCAM 的表达低于模型对照组及5-Fu 组,差异有统计学意义(P<0.05)。益气补肾组及协同组瘤体组织中 Notch1

  7. Oligometastatic non-small-cell lung cancer: current treatment strategies

    Directory of Open Access Journals (Sweden)

    Richard PJ

    2016-11-01

    Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

  8. Influence of cell voltage and current on sulfur poisoning behavior of solid oxide fuel cells

    Science.gov (United States)

    Cheng, Zhe; Zha, Shaowu; Liu, Meilin

    The sulfur poisoning behavior of nickel-yttria stabilized zirconia (YSZ) cermet anodes in solid oxide fuel cells (SOFCs) was investigated under both potentiostatic and galvanostatic conditions. While the observed relative drop in cell power output caused by sulfur poisoning decreases as the cell-terminal voltage is lowered potentiostatically (thus more current passing through the cell), it increases as more current is drawn from the cell galvanostatically (thus leading to lower terminal voltage). The apparent contradictory trends in relative performance loss due to sulfur poisoning are explained using a simple equivalent circuit analysis, which was further validated by impedance measurements of cells before and after poisoning by trace amounts of hydrogen sulfide (H 2S) under different conditions. Results suggest that the relative increase in cell internal resistance caused by sulfur poisoning is smaller when more current is drawn from the cell (or the cell-terminal voltage is lowered) under either potentiostatic or galvanostatic conditions. Thus, the increase in anode polarization resistance, not the drop in cell power output, should be used to describe the degree of sulfur poisoning in order to avoid any confusion.

  9. Involvement of plant stem cells or stem cell-like cells in dedifferentiation

    Directory of Open Access Journals (Sweden)

    Fangwei eJiang

    2015-11-01

    Full Text Available Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation.

  10. Artificial three-dimensional niches deconstruct pancreas development in vitro.

    Science.gov (United States)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Manuel; Gobaa, Samy; Ranga, Adrian; Semb, Henrik; Lutolf, Matthias; Grapin-Botton, Anne

    2013-11-01

    In the context of a cellular therapy for diabetes, methods for pancreatic progenitor expansion and subsequent differentiation into insulin-producing beta cells would be extremely valuable. Here we establish three-dimensional culture conditions in Matrigel that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the medium composition we generate either hollow spheres, which are mainly composed of pancreatic progenitors, or complex organoids that spontaneously undergo pancreatic morphogenesis and differentiation. The in vitro maintenance and expansion of pancreatic progenitors require active Notch and FGF signaling, thus recapitulating in vivo niche signaling interactions. Our experiments reveal new aspects of pancreas development, such as a community effect by which small groups of cells better maintain progenitor properties and expand more efficiently than isolated cells, as well as the requirement for three-dimensionality. Finally, growth conditions in chemically defined biomaterials pave the way for testing the biophysical and biochemical properties of the niche that sustains pancreatic progenitors.

  11. Structural ECM components in the premetastatic and metastatic niche.

    Science.gov (United States)

    Høye, Anette M; Erler, Janine T

    2016-06-01

    The aim of this review is to give an overview of the extracellular matrix (ECM) components that are important for creating structural changes in the premetastatic and metastatic niche. The successful arrival and survival of cancer cells that have left the primary tumor and colonized distant sites depends on the new microenvironment they encounter. The primary tumor itself releases factors into the circulation that travel to distant organs and then initiate structural changes, both non-enzymatic and enzymatic, to create a favorable niche for the disseminating tumor cells. Therapeutic strategies aimed at targeting cell-ECM interactions may well be one of the best viable approaches to combat metastasis and thus improve patient care.

  12. A blueprint for engineering cell fate: current technologies to reprogram cell identity

    Institute of Scientific and Technical Information of China (English)

    Samantha A Morris; George Q Daley

    2013-01-01

    Human diseases such as heart failure,diabetes,neurodegenerative disorders,and many others result from the deficiency or dysfunction of critical cell types.Strategies for therapeutic tissue repair or regeneration require the in vitro manufacture of clinically relevant quantities of defined cell types.In addition to transplantation therapy,the generation of otherwise inaccessible cells also permits disease modeling,toxicology testing and drug discovery in vitro.In this review,we discuss current strategies to manipulate the identity of abundant and accessible cells by differentiation from an induced pluripotent state or direct conversion between differentiated states.We contrast these approaches with recent advances employing partial reprogramming to facilitate lineage switching,and discuss the mechanisms underlying the engineering of cell fate.Finally,we address the current limitations of the field and how the resulting cell types can be assessed to ensure the production of medically relevant populations.

  13. Mapping of potential neurogenic niche in the human temporal lobe

    Directory of Open Access Journals (Sweden)

    Adriano Barreto Nogueira

    2014-10-01

    Full Text Available The subgranular zone (SGZ of the dentate gyrus and the subventricular zone (SVZ are known neurogenic niches in adult mammals. Nonetheless, the existence of neurogenic niches in adult humans is controversial. We hypothesized that mapping neurogenic niches in the human temporal lobe could clarify this issue. Neurogenic niches and neurogenesis were investigated in 28 temporal lobes via immunostaining for nestin and doublecortin (DCX, respectively. Nestin was observed in a continuous layer formed by the SVZ, the subpial zone of the medial temporal lobe and the SGZ, terminating in the subiculum. In the subiculum, remarkable DCX expression was observed through the principal efferent pathway of the hippocampus to the fimbria. A possible explanation for the results is that the SVZ, the subpial zone of the medial temporal lobe and the SGZ form a unit containing neural stem cells that differentiate into neurons in the subiculum. Curiously, the area previously identified as the human rostral migratory stream may in truth be the fornix, which contains axons that originate in the subiculum. This study suggests that neurogenesis may occur in an orchestrated manner in a broad area of the human temporal lobe.

  14. Trophic niche shifts driven by phytoplankton in sandy beach ecosystems

    Science.gov (United States)

    Bergamino, Leandro; Martínez, Ana; Han, Eunah; Lercari, Diego; Defeo, Omar

    2016-10-01

    Stable isotopes (δ13C and δ15N) together with chlorophyll a and densities of surf diatoms were used to analyze changes in trophic niches of species in two sandy beaches of Uruguay with contrasting morphodynamics (i.e. dissipative vs. reflective). Consumers and food sources were collected over four seasons, including sediment organic matter (SOM), suspended particulate organic matter (POM) and the surf zone diatom Asterionellopsis guyunusae. Circular statistics and a Bayesian isotope mixing model were used to quantify food web differences between beaches. Consumers changed their trophic niche between beaches in the same direction of the food web space towards higher reliance on surf diatoms in the dissipative beach. Mixing models indicated that A. guyunusae was the primary nutrition source for suspension feeders in the dissipative beach, explaining their change in dietary niche compared to the reflective beach where the proportional contribution of surf diatoms was low. The high C/N ratios in A. guyunusae indicated its high nutritional value and N content, and may help to explain the high assimilation by suspension feeders at the dissipative beach. Furthermore, density of A. guyunusae was higher in the dissipative than in the reflective beach, and cell density was positively correlated with chlorophyll a only in the dissipative beach. Therefore, surf diatoms are important drivers in the dynamics of sandy beach food webs, determining the trophic niche space and productivity. Our study provides valuable insights on shifting foraging behavior by beach fauna in response to changes in resource availability.

  15. Platelet-Rich Plasma Favors Proliferation of Canine Adipose-Derived Mesenchymal Stem Cells in Methacrylate-Endcapped Caprolactone Porous Scaffold Niches

    Directory of Open Access Journals (Sweden)

    Victoria Moreno-Manzano

    2012-08-01

    Full Text Available Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy ethyl ester (CLMA scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration.

  16. Target Article with Commentaries: Developmental Niche Construction

    Science.gov (United States)

    Flynn, Emma G.; Laland, Kevin N.; Kendal, Rachel L.; Kendal, Jeremy R.

    2013-01-01

    Niche construction is the modification of components of the environment through an organism's activities. Humans modify their environments mainly through ontogenetic and cultural processes, and it is this reliance on learning, plasticity and culture that lends human niche construction a special potency. In this paper we aim to facilitate…

  17. A Niche Width Model of Optimal Specialization

    NARCIS (Netherlands)

    Bruggeman, Jeroen; Ó Nualláin, Breanndán

    2000-01-01

    Niche width theory, a part of organizational ecology, predicts whether “specialist” or “generalist” forms of organizations have higher “fitness,” in a continually changing environment. To this end, niche width theory uses a mathematical model borrowed from biology. In this paper, we first loosen th

  18. Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

    Institute of Scientific and Technical Information of China (English)

    RUAN Yanfei; LIU Nian; ZHOU Qiang; LI Yang; WANG Lin

    2005-01-01

    Summary: The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P0.05). The lower IK,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

  19. Current-Induced Transistor Sensorics with Electrogenic Cells.

    Science.gov (United States)

    Fromherz, Peter

    2016-04-25

    The concepts of transistor recording of electroactive cells are considered, when the response is determined by a current-induced voltage in the electrolyte due to cellular activity. The relationship to traditional transistor recording, with an interface-induced response due to interactions with the open gate oxide, is addressed. For the geometry of a cell-substrate junction, the theory of a planar core-coat conductor is described with a one-compartment approximation. The fast electrical relaxation of the junction and the slow change of ion concentrations are pointed out. On that basis, various recording situations are considered and documented by experiments. For voltage-gated ion channels under voltage clamp, the effects of a changing extracellular ion concentration and the enhancement/depletion of ion conductances in the adherent membrane are addressed. Inhomogeneous ion conductances are crucial for transistor recording of neuronal action potentials. For a propagating action potential, the effects of an axon-substrate junction and the surrounding volume conductor are distinguished. Finally, a receptor-transistor-sensor is described, where the inhomogeneity of a ligand-activated ion conductance is achieved by diffusion of the agonist and inactivation of the conductance. Problems with regard to a development of reliable biosensors are mentioned.

  20. Current status and perspectives of cell therapy in Chagas disease

    Directory of Open Access Journals (Sweden)

    Milena Botelho Pereira Soares

    2009-07-01

    Full Text Available One century after its discovery, Chagas disease, caused by the protozoan, Trypanosoma cruzi, remains a major health problem in Latin America. Mortality and morbidity are mainly due to chronic processes that lead to dysfunction of the cardiac and digestive systems. About one third of the chronic chagasic individuals have or will develop the symptomatic forms of the disease, with cardiomyopathy being the most common chronic form. This is a progressively debilitating disease for which there are no currently available effective treatments other than heart transplantation. Like in other cardiac diseases, tissue engineering and cell therapy have been investigated in the past few years as a means of recovering the heart function lost as a consequence of chronic damage caused by the immune-mediated pathogenic mechanisms elicited in individuals with chronic chagasic cardiomyopathy. Here we review the studies of cell therapy in animal models and patients with chronic Chagas disease and the perspectives of the recovery of the heart function lost due to infection with T. cruzi.

  1. WOX5-1AA17 Feedback Circuit-Mediated CellularAuxin Response Is Crucial for the Patterning ofRoot Stem Cell Niches in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    In plants, the patterning of stem cell-enriched meristems requires a graded auxin response maximum thatemerges from the concerted action of polar auxin transport, auxin biosynthesis, auxin metabolism, and cellular auxinresponse machinery. However, mechanisms underlying this auxin response maximum-mediated root stem cell mainte-nance are not fully understood. Here, we present unexpected evidence that WUSCHEL-RELATED HOMEOBOX 5 (WOX5)transcription factor modulates expression of auxin biosynthetic genes in the quiescent center (QC) of the root and thusprovides a robust mechanism for the maintenance of auxin response maximum in the root tip. This WOX5 action is bal-anced through the activity of indole-3-acetic acid 17 (IAA17) auxin response repressor. Our combined genetic, cell biol-ogy, and computational modeling studies revealed a previously uncharacterized feedback loop linking WOX5-mediatedauxin production to IAA17-dependent repression of auxin responses. This WOX5-1AA17 feedback circuit further assuresthe maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stemcell (DSC) populations. Our experimental studies and in silico computer simulations both demonstrate that the WOX5-iAA17 feedback circuit is essential for the maintenance of auxin gradient in the root tip and the auxin-mediated root DSCdifferentiation.

  2. Roles of metalloproteases in metastatic niche.

    Science.gov (United States)

    Rucci, N; Sanità, P; Angelucci, A

    2011-11-01

    Metalloproteinases (MMPs) are a cluster of at least 23 enzymes belonging to the more wide family of endopeptidases called Metzincins, whose structure is characterized by the presence of a zinc ion at the catalytic site. Although the general view of MMPs as physiologic scissors involved in extracellular matrix (ECM) degradation and tissue remodeling is still valid, additional functions have recently emerged, including the ability to cleave non ECM molecules such as growth factors, cytokines and chemokines from their membrane-anchored proforms. These functions are utilized by tumor cells and are fundamental in the determination of tumor progression and invasion. The effect of MMPs activity in cancer progression has been traditionally associated with the acquisition by tumor cells of an invasive phenotype, an indispensable requisite for the metastatic spreading of cancer cells. In addition to the traditional view, a new role for MMPs in creating a favourable microenvironment has been proposed, so that MMPs are not only involved in cell invasion, but also in signaling pathways that control cell growth, inflammation, or angiogenesis. Finally, recent evidence suggest a role of MMPs in the so called "pre-metastatic niche" that is the hypothesis of an early distant modification of the premetastatic site by primary cancer cells. This new hypothesis is changing our traditional view about MMPs and provides important insights into the effective time window for the therapeutic use of MMP inhibitors. In this review we provide the main available data about the ability of MMPs in creating a suitable microenvironment for tumor growth in metastatic sites and we indicate the implication of these data on the potential use of MMP inhibitors in the metastatic therapy.

  3. The probabilistic niche model reveals substantial variation in the niche structure of empirical food webs.

    Science.gov (United States)

    Williams, Richard J; Purves, Drew W

    2011-09-01

    The structure of food webs, complex networks of interspecies feeding interactions, plays a crucial role in ecosystem resilience and function, and understanding food web structure remains a central problem in ecology. Previous studies have shown that key features of empirical food webs can be reproduced by low-dimensional "niche" models. Here we examine the form and variability of food web niche structure by fitting a probabilistic niche model to 37 empirical food webs, a much larger number of food webs than used in previous studies. The model relaxes previous assumptions about parameter distributions and hierarchy and returns parameter estimates for each species in each web. The model significantly outperforms previous niche model variants and also performs well for several webs where a body-size-based niche model performs poorly, implying that traits other than body size are important in structuring these webs' niche space. Parameter estimates frequently violate previous models' assumptions: in 19 of 37 webs, parameter values are not significantly hierarchical, 32 of 37 webs have nonuniform niche value distributions, and 15 of 37 webs lack a correlation between niche width and niche position. Extending the model to a two-dimensional niche space yields networks with a mixture of one- and two-dimensional niches and provides a significantly better fit for webs with a large number of species and links. These results confirm that food webs are strongly niche-structured but reveal substantial variation in the form of the niche structuring, a result with fundamental implications for ecosystem resilience and function.

  4. Ecological niches of open ocean phytoplankton taxa

    DEFF Research Database (Denmark)

    Brun, Philipp Georg; Vogt, Meike; Payne, Mark;

    2015-01-01

    We characterize the realized ecological niches of 133 phytoplankton taxa in the open ocean based on observations from the MAREDAT initiative and a statistical species distribution model (MaxEnt). The models find that the physical conditions (mixed layer depth, temperature, light) govern large...... conditions in the open ocean. Our estimates of the realized niches roughly match the predictions of Reynolds' C-S-R model for the global ocean, namely that taxa classified as nutrient stress tolerant have niches at lower nutrient and higher irradiance conditions than light stress tolerant taxa. Yet...

  5. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential.

    Science.gov (United States)

    Ishii, Tetsuya

    2014-10-13

    Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS) cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART) that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  6. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  7. Niching method using clustering crowding

    Institute of Scientific and Technical Information of China (English)

    GUO Guan-qi; GUI Wei-hua; WU Min; YU Shou-yi

    2005-01-01

    This study analyzes drift phenomena of deterministic crowding and probabilistic crowding by using equivalence class model and expectation proportion equations. It is proved that the replacement errors of deterministic crowding cause the population converging to a single individual, thus resulting in premature stagnation or losing optional optima. And probabilistic crowding can maintain equilibrium multiple subpopulations as the population size is adequate large. An improved niching method using clustering crowding is proposed. By analyzing topology of fitness landscape using hill valley function and extending the search space for similarity analysis, clustering crowding determines the locality of search space more accurately, thus greatly decreasing replacement errors of crowding. The integration of deterministic and probabilistic replacement increases the capacity of both parallel local hill climbing and maintaining multiple subpopulations. The experimental results optimizing various multimodal functions show that,the performances of clustering crowding, such as the number of effective peaks maintained, average peak ratio and global optimum ratio are uniformly superior to those of the evolutionary algorithms using fitness sharing, simple deterministic crowding and probabilistic crowding.

  8. Periosteum derived stem cells for regenerative medicine proposals: boosting current knowledge

    Institute of Scientific and Technical Information of China (English)

    Concetta; Ferretti; Monica; Mattioli-Belmonte

    2014-01-01

    Periosteum is a thin fibrous layer that covers most bones. It resides in a dynamic mechanically loaded environment and provides a niche for pluripotent cells and a source for molecular factors that modulate cell behaviour. Elucidating periosteum regenerative poten-tial has become a hot topic in orthopaedics. This review discusses the state of the art of osteochondral tissue engineering rested on periosteum derived progenitor cells(PDPCs) and suggests upcoming research direc-tions. Periosteal cells isolation, characterization and migration in the site of injury, as well as their differen-tiation, are analysed. Moreover, the role of cell mecha-nosensing and its contribution to matrix organization, bone microarchitecture and bone stenght is examined. In this regard the role of periostin and its upregulation under mechanical stress in order to preserve PDPC sur-vival and bone tissue integrity is contemplated. The re-view also summarized the role of the periosteum in the field of dentistry and maxillofacial reconstruction. The involvement of microRNAs in osteoblast differentiation and in endogenous tissue repair is explored as well. Fi-nally the novel concept of a guided bone regenerationbased on the use of periosteum itself as a smart mate-rial and the realization of constructs able to mimic the extracellular matrix features is talked out. Additionally, since periosteum can differentiate into insulin produc-ing cells it could be a suitable source in allogenic trans-plantations. That innovative applications would takeadvantage from investigations aimed to assess PDPCimmune privilege.

  9. Investigation of the current break-down phenomena in solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, S.K.; Srinivasamurthy, N.; Agrawal, B.L. [Power Systems Group, ISRO Satellite Centre, Bangalore (India)

    1996-08-15

    Observed reverse current-voltage characteristics of the single crystal silicon and gallium arsenide solar cells have been analyzed. Physical mechanisms behind the junction break-down in silicon cells and current break-down in gallium arsenide cells have been identified. Preliminary estimates of the diffusion capacitance in GaAs cells have been presented

  10. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2009

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.; Gikakis, C.

    2009-10-01

    This report documents progress in meeting the technological challenges of fuel cell propulsion for transportation based on current fuel cell transit bus demonstrations and plans for more fuel cell transit buses and hydrogen infrastructure.

  11. CROSS DRIFT ALCOVE/NICHE UTILITIES ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    S. Goodin

    1999-07-08

    The purpose of this analysis is to provide the design basis and general arrangement requirements of the non-potable water, waste water, compressed air and ventilation (post excavation) utilities required in support of the Cross Drift alcoves and niches.

  12. Red blood cell transfusion in preterm neonates: current perspectives

    Directory of Open Access Journals (Sweden)

    Chirico G

    2014-06-01

    were evaluated, the girls in the liberal group had the most significant abnormalities. In conclusion, it would seem preferable to adopt restrictive criteria. Current recommendation on transfusion therapy should be revised to take into account this suggestion.Keywords: preterm neonates, red blood cells, transfusion, anemia

  13. CLIMBER: Climatic niche characteristics of the butterflies in Europe

    Science.gov (United States)

    Schweiger, Oliver; Harpke, Alexander; Wiemers, Martin; Settele, Josef

    2014-01-01

    Abstract Detailed information on species’ ecological niche characteristics that can be related to declines and extinctions is indispensable for a better understanding of the relationship between the occurrence and performance of wild species and their environment and, moreover, for an improved assessment of the impacts of global change. Knowledge on species characteristics such as habitat requirements is already available in the ecological literature for butterflies, but information about their climatic requirements is still lacking. Here we present a unique dataset on the climatic niche characteristics of 397 European butterflies representing 91% of the European species (see Appendix). These characteristics were obtained by combining detailed information on butterfly distributions in Europe (which also led to the ‘Distribution Atlas of Butterflies in Europe’) and the corresponding climatic conditions. The presented dataset comprises information for the position and breadth of the following climatic niche characteristics: mean annual temperature, range in annual temperature, growing degree days, annual precipitation sum, range in annual precipitation and soil water content. The climatic niche position is indicated by the median and mean value for each climate variable across a species’ range, accompanied by the 95% confidence interval for the mean and the number of grid cells used for calculations. Climatic niche breadth is indicated by the standard deviation and the minimum and maximum values for each climatic variable across a species’ range. Database compilation was based on high quality standards and the data are ready to use for a broad range of applications. It is already evident that the information provided in this dataset is of great relevance for basic and applied ecology. Based on the species temperature index (STI, i.e. the mean temperature value per species), the community temperature index (CTI, i.e. the average STI value across the species

  14. Myoepithelial cells: Current perspectives in salivary gland tumors

    Directory of Open Access Journals (Sweden)

    C Pramod Redder

    2013-01-01

    Full Text Available Myoepithelial cells are normal constituent of the salivary acini and smaller ducts, and are found between the epithelial cells and the basement membrane. Microscopic examination shows that myoepithelial cells are thin and spindle-shaped and situated between the basement membrane and epithelial cells. Ultrastructurally they possess a number of cytoplasmic processes that extend between and over the acinar and ductal-lining cells. They display features of both smooth muscle and epithelium, such as numerous microfilaments with focal densities in the cytoplasmic processes, and desmosomes which attach the myoepithelial to the epithelial cells. Neoplastic myoepithelial cells in both benign and malignant tumors can take several forms, including epithelioid, spindle, plasmacytoid, and clear, and this variability largely accounts for difficulties in histopathological diagnosis. This review article highlights the role of myoepithelial cells in salivary gland tumors.

  15. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    OpenAIRE

    2011-01-01

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cel...

  16. A threshold sodium current in pyramidal cells in rat hippocampus.

    Science.gov (United States)

    French, C R; Gage, P W

    1985-05-23

    Maintained, inward currents were activated by small depolarizations from the resting membrane potential (-50 to -60 mV) in voltage-clamped, pyramidal neurons in rat hippocampal slices. The currents were apparently Na currents as they were blocked by tetrodotoxin or removal of extracellular Na and were not affected by Cd. They showed little decrease in amplitude during prolonged depolarizations. The increase in Na conductance with depolarization was sigmoidal, with half-maximum conductance at about -50 mV, and saturated at -20 to -30 mV. This 'threshold' Na current may be involved in setting patterns of repetitive firing of action potentials.

  17. Biodiversity influences plant productivity through niche-efficiency.

    Science.gov (United States)

    Liang, Jingjing; Zhou, Mo; Tobin, Patrick C; McGuire, A David; Reich, Peter B

    2015-05-05

    The loss of biodiversity is threatening ecosystem productivity and services worldwide, spurring efforts to quantify its effects on the functioning of natural ecosystems. Previous research has focused on the positive role of biodiversity on resource acquisition (i.e., niche complementarity), but a lack of study on resource utilization efficiency, a link between resource and productivity, has rendered it difficult to quantify the biodiversity-ecosystem functioning relationship. Here we demonstrate that biodiversity loss reduces plant productivity, other things held constant, through theory, empirical evidence, and simulations under gradually relaxed assumptions. We developed a theoretical model named niche-efficiency to integrate niche complementarity and a heretofore-ignored mechanism of diminishing marginal productivity in quantifying the effects of biodiversity loss on plant productivity. Based on niche-efficiency, we created a relative productivity metric and a productivity impact index (PII) to assist in biological conservation and resource management. Relative productivity provides a standardized measure of the influence of biodiversity on individual productivity, and PII is a functionally based taxonomic index to assess individual species' inherent value in maintaining current ecosystem productivity. Empirical evidence from the Alaska boreal forest suggests that every 1% reduction in overall plant diversity could render an average of 0.23% decline in individual tree productivity. Out of the 283 plant species of the region, we found that large woody plants generally have greater PII values than other species. This theoretical model would facilitate the integration of biological conservation in the international campaign against several pressing global issues involving energy use, climate change, and poverty.

  18. Potassium currents in auditory hair cells of the frog basilar papilla.

    Science.gov (United States)

    Smotherman, M S; Narins, P M

    1999-06-01

    The whole-cell patch-clamp technique was used to identify and characterize ionic currents in isolated hair cells of the leopard frog basilar papilla (BP). This end organ is responsible for encoding the upper limits of a frog's spectral sensitivity (1.25-2.0 kHz in the leopard frog). Isolated BP hair cells are the smallest hair cells in the frog auditory system, with spherical cell bodies typically less than 20 microm in diameter and exhibiting whole-cell capacitances of 4-7 pF. Hair cell zero-current resting potentials (Vz) varied around a mean of -65 mV. All hair cells possessed a non-inactivating, voltage-dependent calcium current (I(Ca)) that activates above a threshold of -55 mV. Similarly all hair cells possessed a rapidly activating, outward, calcium-dependent potassium current (I(K)(Ca)). Most hair cells also possessed a slowly activating, outward, voltage-dependent potassium current (I(K)), which is approximately 80% inactive at the hair cell Vz, and a fast-activating, inward-rectifying potassium current (I(K1)) which actively contributes to setting Vz. In a small subset of cells I(K) was replaced by a fast-inactivating, voltage-dependent potassium current (I(A)), which strongly resembled the A-current observed in hair cells of the frog sacculus and amphibian papilla. Most cells have very similar ionic currents, suggesting that the BP consists largely of one homogeneous population of hair cells. The kinetic properties of the ionic currents present (in particular the very slow I(K)) argue against electrical tuning, a specialized spectral filtering mechanism reported in the hair cells of birds, reptiles, and amphibians, as a contributor to frequency selectivity of this organ. Instead BP hair cells reflect a generalized strategy for the encoding of high-frequency auditory information in a primitive, mechanically tuned, terrestrial vertebrate auditory organ.

  19. Hybrid Direct Carbon Fuel Cell Performance with Anode Current Collector Material

    DEFF Research Database (Denmark)

    Deleebeeck, Lisa; Kammer Hansen, Kent

    2015-01-01

    The influence of the current collector on the performance of a hybrid direct carbon fuel cell (HDCFC), consisting of solid oxide fuel cell (SOFC) with a molten carbonate-carbon slurry in contact with the anode, has been investigated using current-voltage curves. Four different anode current...

  20. Modeling and control of the output current of a Reformed Methanol Fuel Cell system

    DEFF Research Database (Denmark)

    Justesen, Kristian Kjær; Andreasen, Søren Juhl; Pasupathi, Sivakumar

    2015-01-01

    In this work, a dynamic Matlab SIMULINK model of the relationship between the fuel cell current set point of a Reformed Methanol Fuel Cell system and the output current of the system is developed. The model contains an estimated fuel cell model, based on a polarization curve and assumed first order...

  1. Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells.

    Science.gov (United States)

    Kramer, R H; Mokkapatti, R; Levitan, E S

    1994-01-01

    Caffeine elicits physiological responses in a variety of cell types by triggering the mobilization of Ca2+ from intracellular organelles. Here we investigate the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase superimposed upon a sustained inhibition. While the transient increase coincides with a rise in [Ca2+]i, the sustained inhibition of IK(Ca) is correlated with a sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine. Unlike the caffeine effect, the TRH-induced inhibition "washes-out" under whole-cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators. Likewise, the ryanodine-induced inhibition desensitizes while the caffeine-induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single-channel recordings show that caffeine reduces mean open time without affecting single-channel conductance of L-type channels. Hence the effects of caffeine on ion channels in GH3 cells are attributable both to mobilization of intracellular Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.

  2. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells fo

  3. Climatic niche divergence and habitat suitability of eight alien invasive weeds in China under climate change.

    Science.gov (United States)

    Wan, Ji-Zhong; Wang, Chun-Jing; Tan, Jing-Fang; Yu, Fei-Hai

    2017-03-01

    Testing climatic niche divergence and modeling habitat suitability under conditions of climate change are important for developing strategies to limit the introduction and expansion of alien invasive weeds (AIWs) and providing important ecological and evolutionary insights. We assessed climatic niches in both native and invasive ranges as well as habitat suitability under climate change for eight representative Chinese AIWs from the American continent. We used climatic variables associated with occurrence records and developed ecological niche models with Maxent. Interestingly, the climatic niches of all eight AIWs diverged significantly between the native and invasive ranges (the American continent and China). Furthermore, the AIWs showed larger climatic niche breadths in the invasive ranges than in the native ranges. Our results suggest that climatic niche shifts between native and invasive ranges occurred. Thus, the occurrence records of both native and invasive regions must be considered when modeling and predicting the spatial distributions of AIWs under current and future climate scenarios. Owing to high habitat suitability, AIWs were more likely to expand into regions of low latitude, and future climate change was predicted to result in a shift in the AIWs in Qinghai and Tibet (regions of higher altitude) as well as Heilongjiang, Jilin, Liaoning, Inner Mongolia, and Gansu (regions of higher latitude). Our results suggest that we need measures to prevent and control AIW expansion at the country-wide level.

  4. Expansion of hematopoietic stem cells for transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Schuster Jessica A

    2012-05-01

    Full Text Available Abstract Hematopoietic stem cells (HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The expansion of HSCs has remained an important goal to develop advanced cell therapies for bone marrow transplantation and many blood disorders. Over the last several decades, there have been numerous attempts to expand HSCs in vitro using purified growth factors that are known to regulate HSCs. However, these attempts have been met with limited success for clinical applications. New developments in the HSC expansion field coupled with gene therapy and stem cell transplant should encourage progression in attractive treatment options for many disorders including hematologic conditions, immunodeficiencies, and genetic disorders.

  5. Stable isotope evidence for trophic niche partitioning in a South African savanna rodent community

    Institute of Scientific and Technical Information of China (English)

    Jacqueline CODRON; Kevin J DUFFY; Nico L AVENANT; Matt SPONHEIMER; Jennifer LEICHLITER; Oliver PAINE; Paul SANDBERG; Daryl CODRON

    2015-01-01

    Species’ partitioning of resources remains one of the most integral components for understanding community assem-bly. Analysis of stable carbon and nitrogen isotopes in animal tissues has the potential to help resolve patterns of partitioning be-cause these proxies represent the individual’s diet and trophic niche, respectively. Using free-ranging rodents in a southern Afri-can savanna as a model community, we find that syntopic species within habitats occupy distinct isotope niches. Moreover, spe-cies with strongly overlapping isotope niches did not overlap in their spatial distribution patterns, suggesting an underlying effect of competitive exclusion. Niche conservatism appears to characterize the behaviour of most species in our sample – with little or no observed changes across habitats – with the exception of one species,Mastomys coucha. This species displayed a generalist distribution, being found in similar abundances across a variety of habitats. This spatial pattern was coupled with a generalist isotope niche that shifted across habitats, likely in response to changes in species composition over the same spatial gradient. The case forM. coucha supports contentions that past competition effects played a significant evolutionary role in shaping community structures of today, including the absence of strong interspecific niche overlaps within particular habitats. Our study highlights the value of stable isotope approaches to help resolve key questions in community ecology, and moreover introduces novel ana-lytical approaches to quantifying isotope niche breadths and niche overlaps that are easily comparable with traditional metrices [Current Zoology 61 (3): 397–441, 2015].

  6. Epigenetic regulation of stemness maintenance in theneurogenic niches

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In the adult mouse brain, the subventricular zonelining the lateral ventricles and the subgranular zonein the dentate gyrus of the hippocampus are twozones that contain neural stem cells (NSCs) withthe capacity to give rise to neurons and glia duringthe entire life of the animal. Spatial and temporalregulation of gene expression in the NSCs populationis established and maintained by the coordinatedinteraction between transcription factors and epigeneticregulators which control stem cell fate. Epigenetic mechanismsare heritable alterations in genome functionthat do not involve changes in DNA sequence itself butthat modulate gene expression, acting as mediatorsbetween the environment and the genome. At themolecular level, those epigenetic mechanisms comprisechemical modifications of DNA such as methylation,hydroxymethylation and histone modifications neededfor the maintenance of NSC identity. Genomic imprintingis another normal epigenetic process leading to parentalspecificexpression of a gene, known to be implicatedin the control of gene dosage in the neurogenic niches.The generation of induced pluripotent stem cells fromNSCs by expression of defined transcription factors,provide key insights into fundamental principles ofstem cell biology. Epigenetic modifications can alsooccur during reprogramming of NSCs to pluripotencyand a better understanding of this process will helpto elucidate the mechanisms required for stem cellmaintenance. This review takes advantage of recentstudies from the epigenetic field to report knowledgeregarding the mechanisms of stemness maintenance ofneural stem cells in the neurogenic niches.

  7. Investigation of In Vitro Bone Cell Adhesion and Proliferation on Ti Using Direct Current Stimulation.

    Science.gov (United States)

    Bodhak, Subhadip; Bose, Susmita; Kinsel, William C; Bandyopadhyay, Amit

    2012-12-01

    Our objective was to establish an in vitro cell culture protocol to improve bone cell attachment and proliferation on Ti substrate using direct current stimulation. For this purpose, a custom made electrical stimulator was developed and a varying range of direct currents, from 5 to 25 µA, were used to study the current stimulation effect on bone cells cultured on conducting Ti samples in vitro. Cell-materials interaction was studied for a maximum of 5 days by culturing with human fetal osteoblast cells (hFOB). The direct current was applied in every 8 h time interval and the duration of electrical stimulation was kept constant at 15 min for all cases. In vitro results showed that direct current stimulation significantly favored bone cell attachment and proliferation in comparison to nonstimulated Ti surface. Immunochemistry and confocal microscopy results confirmed that the cell adhesion was most pronounced on 25 µA direct current stimulated Ti surfaces as hFOB cells expressed higher vinculin protein with increasing amount of direct current. Furthermore, MTT assay results established that cells grew 30% higher in number under 25 µA electrical stimulation as compared to nonstimulated Ti surface after 5 days of culture period. In this work we have successfully established a simple and cost effective in vitro protocol offering easy and rapid analysis of bone cell-materials interaction which can be used in promotion of bone cell attachment and growth on Ti substrate using direct current electrical stimulation in an in vitro model.

  8. Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies

    Directory of Open Access Journals (Sweden)

    Michel Haagdorens

    2016-01-01

    Full Text Available Severe ocular surface disease can result in limbal stem cell deficiency (LSCD, a condition leading to decreased visual acuity, photophobia, and ocular pain. To restore the ocular surface in advanced stem cell deficient corneas, an autologous or allogenic limbal stem cell transplantation is performed. In recent years, the risk of secondary LSCD due to removal of large limbal grafts has been significantly reduced by the optimization of cultivated limbal epithelial transplantation (CLET. Despite the great successes of CLET, there still is room for improvement as overall success rate is 70% and visual acuity often remains suboptimal after successful transplantation. Simple limbal epithelial transplantation reports higher success rates but has not been performed in as many patients yet. This review focuses on limbal epithelial stem cells and the pathophysiology of LSCD. State-of-the-art therapeutic management of LSCD is described, and new and evolving techniques in ocular surface regeneration are being discussed, in particular, advantages and disadvantages of alternative cell scaffolds and cell sources for cell based ocular surface reconstruction.

  9. Immobilized cell technology in beer brewing: Current experience and results

    Directory of Open Access Journals (Sweden)

    Leskošek-Čukalov Ida J.

    2005-01-01

    Full Text Available Immobilized cell technology (ICT has been attracting continual attention in the brewing industry over the past 30 years. Some of the reasons are: faster fermentation rates and increased volumetric productivity, compared to those of traditional beer production based on freely suspended cells, as well as the possibility of continuous operation. Nowadays, ICT technology is well established in secondary fermentation and alcohol- free and low-alcohol beer production. In main fermentation, the situation is more complex and this process is still under scrutiny on both the lab and pilot levels. The paper outlines the most important ICT processes developed for beer brewing and provides an overview of carrier materials, bioreactor design and examples of their industrial applications, as well as some recent results obtained by our research group. We investigated the possible applications of polyvinyl alcohol in the form of LentiKats®, as a potential porous matrices carrier for beer fermentation. Given are the results of growth studies of immobilized brewer's yeast Saccharomyces uvarum and the kinetic parameters obtained by using alginate microbeads with immobilized yeast cells and suspension of yeast cells as controls. The results indicate that the immobilization procedure in LentiKat® carriers has a negligible effect on cell viability and growth. The apparent specific growth rate of cells released in medium was comparable to that of freely suspended cells, implying preserved cell vitality. A series of batch fermentations performed in shaken flasks and an air-lift bioreactor indicated that the immobilized cells retained high fermentation activity. The full attenuation in green beer was reached after 48 hours in shaken flasks and less than 24 hours of fermentation in gas-lift bioreactors.

  10. Classification and comparison of niche services for developing strategy of medical tourism in Asian countries.

    Science.gov (United States)

    Chen, Hung-chi; Kuo, Hsin-chih; Chung, Kuo-Piao; Chang, Sophia; Su, Syi; Yang, Ming-chin

    2010-01-01

    , and (3) banned procedures that are not allowed legally in home countries of foreign patients, such as stem cell therapy. In establishing a niche service, a high-quality, nonmedical segment should be integrated as well.

  11. Experiment research on PESV for inhibiting activation of leucemia stem cell in the niche%蝎毒多肽抑制白血病干细胞龛内活化的实验研究

    Institute of Scientific and Technical Information of China (English)

    杨向东; 杨文华; 史哲新; 刘宝山; 高宏; 张蕾; 陈艳鑫

    2011-01-01

    [Objective] To observe the effect of PESV (peptide extract from scorpion venom) for inhibiting the activation of leucemia stem cells (LSC) in the niche. [Methods] LSC were isolated from patients with AML/ALL and stored in the Trans well. Then they were divided into four groups: high-dose group, middle-dose group, low-dose group and the positive control group. After cultured with different concentrations of PESV, the transport ratios of LSC in various concentration groups were computed at different time. [Results] The transport ratios cultured with different concentrations of PESV were (25.01 ±6.83)%, (36.85±3.83)%, (50.73±7.15)%, and there was a significant difference compared with that of the positive control group (49.10±6.12)% (P<0.05). The transport ratio in the high-dose group is more than that of the middle and lose-dose groups. [Conclusion] All different concentrations of PESV have the inhibiting effects against the activation of LSC with a inhibiting intensity depending on the concentrations of PESV.%[目的]观察蝎毒多肽(PESV)抑制白血病干细胞(LSC)在骨髓龛内的活化效应.[方法]分离白血病/急性淋巴细胞白血病(AMUALL)患者LSC,置于Transwell小室中,分为高中低剂量组及对照组,分别加入不同浓度蝎毒多肽后培养,计算不同浓度组及不同时间段的ISC迁移率.[结果]PESV组迁移率分别为(25.01±6.83)%,(36.85±3.83)%,(50.73±7.15)%,与对照组(49.10±6.12)%比较差异具有显著性(P<0.05),高剂量组迁移率高于中低剂量组.[结论]不同浓度PESV均有抑制白血病干细胞活化作用,抑制强度呈浓度依赖.

  12. Current status of Westinghouse tubular solid oxide fuel cell program

    Energy Technology Data Exchange (ETDEWEB)

    Parker, W.G. [Westinghouse Science and Technology Center, Pittsburgh, PA (United States)

    1996-04-01

    In the last ten years the solid oxide fuel cell (SOFC) development program at Westinghouse has evolved from a focus on basic material science to the engineering of fully integrated electric power systems. Our endurance for this cell is 5 to 10 years. To date we have successfully operated at power for over six years. For power plants it is our goal to have operated before the end of this decade a MW class power plant. Progress toward these goals is described.

  13. Langerhans cell histiocytosis: Current concepts in dentistry and case report

    OpenAIRE

    Ramos-Gutierrez, Efraín; Alejo-Gonzalez, Francisco; Ruiz Rodríguez, Socorro; Garrocho Rangel, Arturo; Pozos Guillén, Amaury de Jesús

    2016-01-01

    Langerhans cell histiocytosis (LCH), which is a rare granulomatous pediatric disease of unknown etiology, is characterized by the idiopathic proliferation and accumulation of abnormal and clonal Langerhans cells or their marrow precursors, resulting in localized, solitary or multiple destructive lesions. These lesions are most commonly eosinophilic granuloma, which are found in craniofacial bone structures such as the skull and mandible, skin and other organs. In children, the disease has a v...

  14. Two dimensional simulation of direct methanol fuel cell : a new (embedded) type of current collectors

    OpenAIRE

    Kulikovsky, A. A.; Divisek, J.; Kornyshev, Yu. M.

    2000-01-01

    A two-dimensional numerical model of the direct methanol fuel cell with gas fuel is developed. Simulation of the cell with current collectors of conventional geometry reveal the formation of fuel-depleted, "shaded" regions in the cathode and anode catalyst layers. These regions are positioned in front of current collectors, farther from the gas channel windows. Another disadvantage of the conventional geometry is the concentration of electron current at the edges of current collectors. Based ...

  15. Effect of operating current dependent series resistance on the fill factor of a solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Dadu, Meena; Kapoor, A.; Tripathi, K.N. [Department of Electronic Science, University of Delhi, South Campus, Benito Juarez road, -110 021 New Delhi (India)

    2002-02-01

    The fill factor of a solar cell depends upon the series resistance, reverse saturation current, diode quality factor, operating current and voltage. Since the series resistance itself depends upon the operating current (or voltage), it makes the evaluation of fill factor very complicated. In this paper, we have evaluated the fill factor of a solar cell, taking into account operating current dependence of the series resistance.

  16. Niche Formation in the Mashup Ecosystem

    Directory of Open Access Journals (Sweden)

    Michael Weiss

    2013-05-01

    Full Text Available Mashups enable end-users to "mix and match" data and services available on the web to create applications. Their creation is supported by a complex ecosystem of i data providers who offer open APIs to users, ii users who combine APIs into mashups, and iii platforms, such as the ProgrammableWeb or Mashape, that facilitate the construction and publication of mashups. In this article, we argue that the evolution of the mashup ecosystem can be explained in terms of ecosystem niches anchored around hub or keystone APIs. The members of a niche are focused on an area of specialization (e.g., mapping applications and contribute their knowledge to the value proposition of the ecosystem as a whole. To demonstrate the formation of niches in the mashup ecosystem, we model groups of related mashups as species, and we reconstruct the evolution of mashup species through phylogenetic analysis.

  17. Effects of constant voltage and constant current stress in PCBM:P3HT solar cells

    DEFF Research Database (Denmark)

    Cester, Andrea; Rizzo, Aldo; Bazzega, A.

    2015-01-01

    The aimof this work is the investigation of forward and reverse bias stress effects, cell self-heating and annealing in roll coated organic solar cells with PCBM:P3HT active layer. In reverse bias stress cells show a constant degradation over time. In forward current stress cells alternate degrad...

  18. The Current Immune Function of Hepatic Dendritic Cells

    Institute of Scientific and Technical Information of China (English)

    Willy Hsu; Shang-An Shu; Eric Gershwin; Zhe-Xiong Lian

    2007-01-01

    While only a small percentage of the liver as dendritic cells, they play a major role in the regulation of liver immunity. Four major types of dendritic cell subsets include myeloid CD8α-B220-, lymphoid CD8α+B220-,plasmacytoid CD8α-B220+, and natural killer dendritic cell with CD8α-B220-NK1.1+ phenotype. Although these subsets have slightly different characteristics, they are all poor na(i)ve T cell stimulators. In exchange for their reduced capacity for allostimulation, hepatic DCs are equipped with an enhanced ability to secrete cytokines in response to TLR stimulation. In addition, they have increased level of phagocytosis. Both of these traits suggest hepatic DC as part of the innate immune system. With such a high rate of exposure to the dietary and commensal antigens, it is important for the hepatic DCs to have an enhanced innate response while maintaining a tolerogenic state to avoid chronic inflammation. Only upon secondary infectivity does the hepatic DC activate memory T cells for rapid eradication of recurring pathogen. On the other hand, overly tolerogenic characteristics of hepatic DC may be responsible for the increase prevalence of autoimmunity or liver malignancies.

  19. Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle

    2007-01-01

    Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

  20. Langerhans cell histiocytosis: Current concepts in dentistry and case report

    Science.gov (United States)

    Ramos-Gutiérrez, Efraín; Alejo-González, Francisco; Ruiz-Rodríguez, Socorro; Garrocho-Rangel, José-Arturo

    2016-01-01

    Langerhans cell histiocytosis (LCH), which is a rare granulomatous pediatric disease of unknown etiology, is characterized by the idiopathic proliferation and accumulation of abnormal and clonal Langerhans cells or their marrow precursors, resulting in localized, solitary or multiple destructive lesions. These lesions are most commonly eosinophilic granuloma, which are found in craniofacial bone structures such as the skull and mandible, skin and other organs. In children, the disease has a variable initial presentation, and the clinical course, prognosis and survival are unpredictable. The aims of this report were to present an LCH case in a girl aged 2 years, 8 months and her clinicopathological features, to describe the bucodental management provided, and to discuss special dental considerations of this disease. Key words:Children, dental management, histiocytosis, Langerhans cells. PMID:26855698

  1. Is sodium current present in human sinoatrial node cells?

    NARCIS (Netherlands)

    Verkerk, A.O.; Wilders, R.; van Borren, M.M.G.J.; Tan, H.L.

    2009-01-01

    Pacemaker activity of the sinoatrial node has been studied extensively in various animal species, but is virtually unexplored in man. As such, it is unknown whether the fast sodium current (I-Na) plays a role in the pacemaker activity of the human sinoatrial node. Recently, we had the unique opportu

  2. Characterization of a direct methanol fuel cell using Hilbert curve fractal current collectors

    Energy Technology Data Exchange (ETDEWEB)

    Kuan, Yean-Der [Department of Refrigeration, Air-Conditioning and Energy Engineering, National Chun-Yi University of Technology, NO 35, Lane 215, Section 1, Chung-Shan Road, Taiping City, 411 Taichung County (China); Chang, Jing-Yi [Department of Mechanical and Electro-Mechanical Engineering, Tamkang University, Tamsui, 251 Taipei County (China); Lee, Shi-Min [Department of Aerospace Engineering, Tamkang University, Tamsui, 251 Taipei County (China); Lee, Shah-Rong [Department of Mechanical Engineering, Technology and Science Institute of Northern Taiwan, Peitou, 112 Taipei (China)

    2009-02-01

    The current collector or bi-polar plate is a key component in direct methanol fuel cells (DMFCs). Current collector geometric designs have significant influence on cell performance. This paper presents a continuous type fractal geometry using the Hilbert curve applied to current collector design in a direct methanol fuel cell. The Hilbert curve fractal geometry current collector is named HFCC (Hilbert curve fractal current collector). This research designs the current collector using a first, second and third order open carved HFCC shape. The cell performances of the different current collector geometries were measured and compared. Two important factors, the free open ratio and total perimeter length of the open carved design are discussed. The results show that both the larger free open ratio and longer carved open perimeter length present higher performance. (author)

  3. Characterization of a direct methanol fuel cell using Hilbert curve fractal current collectors

    Science.gov (United States)

    Kuan, Yean-Der; Chang, Jing-Yi; Lee, Shi-Min; Lee, Shah-Rong

    The current collector or bi-polar plate is a key component in direct methanol fuel cells (DMFCs). Current collector geometric designs have significant influence on cell performance. This paper presents a continuous type fractal geometry using the Hilbert curve applied to current collector design in a direct methanol fuel cell. The Hilbert curve fractal geometry current collector is named HFCC (Hilbert curve fractal current collector). This research designs the current collector using a first, second and third order open carved HFCC shape. The cell performances of the different current collector geometries were measured and compared. Two important factors, the free open ratio and total perimeter length of the open carved design are discussed. The results show that both the larger free open ratio and longer carved open perimeter length present higher performance.

  4. Current advances in T-cell-based cancer immunotherapy.

    Science.gov (United States)

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

    2014-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

  5. Electrochemical cells: linking fields and currents with products and reactants

    Science.gov (United States)

    Hutchison, Douglas

    2016-11-01

    The interplay between the electromagnetism and chemistry within an electrochemical cell (a ‘battery’) is modelled in such a way so as to describe both open and closed circuit conditions. It is found that a classical field theory coupled with a generic model of the chemistry can consistently explain the behaviour of the cell and reproduce standard results. But this model also reveals an interesting interplay between time scales (field and chemical) that leads to a capacitive impedance within the cell. The assumption that the stasis associated with the emf results from the inability of ions to overcome the potential barriers near each electrode is abandoned. Rather, the equilibrium is viewed as dynamic and results from a balance between forward and reverse chemical reactions. Ions are able borrow enough energy to overcome the barriers as predicted by quantum theory to fuel the forward reactions. The probability of transmission (i.e. ‘tunnelling’) is calculated using a method based on the energy-time uncertainty principle.

  6. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  7. The pre-metastatic niche: is metastasis random?

    Science.gov (United States)

    Cox, Thomas R; Gartland, Alison; Erler, Janine T

    2012-01-01

    The metastasis of solid tumours is a vastly complex, dynamic and systemic process involving both primary tumour cells as well as a wide array of stromal and vascular cells. The recruitment and activation of host cells by tumours at both the primary and metastatic sites is crucial for successful metastatic dissemination highlighting the systemic nature of disease progression. The appropriation of distant metastatic sites by primary tumours and the generation of so-called pre-metastatic niches have gained much interest in the last decade complementing the century old 'seed and soil' hypothesis. The idea that tumours are capable of pre-defining future sites of metastasis is both exciting and terrifying as we try to understand the dynamic networks associated with solid tumour metastasis. Exactly how a tumour cell can alter the distant metastatic microenvironment is of great importance and will unlock novel strategies for successfully targeting these processes.

  8. The pre-metastatic niche: is metastasis random?

    Science.gov (United States)

    Cox, Thomas R; Gartland, Alison; Erler, Janine T

    2012-01-01

    The metastasis of solid tumours is a vastly complex, dynamic and systemic process involving both primary tumour cells as well as a wide array of stromal and vascular cells. The recruitment and activation of host cells by tumours at both the primary and metastatic sites is crucial for successful metastatic dissemination highlighting the systemic nature of disease progression. The appropriation of distant metastatic sites by primary tumours and the generation of so-called pre-metastatic niches have gained much interest in the last decade complementing the century old 'seed and soil' hypothesis. The idea that tumours are capable of pre-defining future sites of metastasis is both exciting and terrifying as we try to understand the dynamic networks associated with solid tumour metastasis. Exactly how a tumour cell can alter the distant metastatic microenvironment is of great importance and will unlock novel strategies for successfully targeting these processes. PMID:27127624

  9. Short circuit current in indium tin oxide/silicon solar cells

    Science.gov (United States)

    Singh, R.

    1980-09-01

    The short-circuit current density of indium tin oxide/single and polycrystalline silicon solar cells reported by Schunck and Coche (1979) is much higher than other silicon solar cells. It is shown that the short-circuit current density reported in the above reference does not represent the true value of these devices.

  10. UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties.

    Science.gov (United States)

    Wang, Ruihua; MoYung, K C; Zhang, M H; Poon, Karen

    2015-12-01

    Using live eukaryotic cells, including cancer cells, MCF-7 and HCT-116, normal hepatocytes and red blood cells in anode and potassium ferricyanide in cathode of MFC could generate bio-based electric current. Electrons and protons generated from the metabolic reaction in both cytosol and mitochondria contributing to the leaking would mediate the generation of electric current. Both resveratrol (RVT) and 2,4-dinitrophenol (DNP) used to induce proton leak in mitochondria were found to promote electric current production in all cells except red blood cells without mitochondria. Proton leak might be important for electric current production by bringing the charge balance in cells to enhance the further electron leak. The induced electric current by RVT can be blocked by Genipin, an inhibitor of UCP2-mediated proton leak, while that induced by DNP cannot. RVT could reduce reactive oxygen species (ROS) level in cells better than that of DNP. In addition, RVT increased mitochondrial membrane potential (MMP), while DNP decreased it. Results highly suggested the existence of at least two types of electric current that showed different properties. They included UCP2-mediated and non-UCP2-mediated electric current. UCP2-mediated electric current exhibited higher reactive oxygen species (ROS) reduction effect per unit electric current production than that of non-UCP2-mediated electric current. Higher UCP2-mediated electric current observed in cancer cells might contribute to the mechanism of drug resistence. Correlation could not be established between electric current production with either ROS and MMP without distinguishing the types of electric current.

  11. ECRB ALCOVE AND NICHE GROUND SUPPORT ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    J.W. Keifer

    1999-05-09

    The purpose of the analysis is to provide design bases for Enhanced Characterization of the Repository Block (ECRB) alcove and niche ground support drawings. The objective is to evaluate the ESF Alcove Ground Support Analysis (Ref 5.1) to determine if the calculations technically bound the ECRB alcoves and to address specific differences in the conditions and constraints.

  12. Graphene as transparent and current spreading electrode in silicon solar cell

    Directory of Open Access Journals (Sweden)

    Sanjay K. Behura

    2014-11-01

    Full Text Available Fabricated bi-layer graphene (BLG has been studied as transparent and current spreading electrode (TCSE for silicon solar cell, using TCAD-Silvaco 2D simulation. We have carried out comparative study using both Ag grids and BLG as current spreading electrode (CSE and TCSE, respectively. Our study reveals that BLG based solar cell shows better efficiency of 24.85% than Ag-based cell (21.44%, in all of the critical aspects, including generation rate, recombination rate, electric field, potential and quantum efficiency. Further BLG based cell exhibits pronounce rectifying behavior, low saturation current, and good turn-on voltage while studying in dark.

  13. Estimation of current density distribution of PAFC by analysis of cell exhaust gas

    Energy Technology Data Exchange (ETDEWEB)

    Kato, S.; Seya, A. [Fuji Electric Co., Ltd., Ichihara-shi (Japan); Asano, A. [Fuji Electric Corporate, Ltd., Yokosuka-shi (Japan)

    1996-12-31

    To estimate distributions of Current densities, voltages, gas concentrations, etc., in phosphoric acid fuel cell (PAFC) stacks, is very important for getting fuel cells with higher quality. In this work, we leave developed a numerical simulation tool to map out the distribution in a PAFC stack. And especially to Study Current density distribution in the reaction area of the cell, we analyzed gas composition in several positions inside a gas outlet manifold of the PAFC stack. Comparing these measured data with calculated data, the current density distribution in a cell plane calculated by the simulation, was certified.

  14. Efficiency of cellular growth when creating small pockets of electric current along the walls of cells.

    Science.gov (United States)

    Kletetschka, Gunther; Zila, Vojtech; Klimova, Lucie

    2014-04-01

    Pulses up to 11 Tesla magnetic fields may generate pockets of currents along the walls of cellular material and may interfere with the overall ability of cell division. We used prokaryotic cells (Escherichia coli) and eukaryotic cells (murine fibroblasts) and exposed them to magnetic pulses of intensities ranging from 1 millitesla (mT) to 11,000 mT. We found prokaryotic cells to be more sensitive to magnetic field pulses than eukaryotic cells.

  15. Efficiency of Cellular Growth When Creating Small Pockets of Electric Current Along the Walls of Cells

    OpenAIRE

    Kletetschka, Gunther; Zila, Vojtech; Klimova, Lucie

    2014-01-01

    Pulses up to 11 Tesla magnetic fields may generate pockets of currents along the walls of cellular material and may interfere with the overall ability of cell division. We used prokaryotic cells (Escherichia coli) and eukaryotic cells (murine fibroblasts) and exposed them to magnetic pulses of intensities ranging from 1 millitesla (mT) to 11,000 mT. We found prokaryotic cells to be more sensitive to magnetic field pulses than eukaryotic cells.

  16. [Prostate cancer stem cells: advances in current research].

    Science.gov (United States)

    Wu, Gang; Wu, Deng-long

    2015-02-01

    Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.

  17. Sperm cell biology: current perspectives and future prospects

    Institute of Scientific and Technical Information of China (English)

    R John Aitken; Ralf R Henkel

    2011-01-01

    @@ Major advances in biomolecular techniques as well as in the sensitivity and accuracy of mass spectrometers are transform-ing the scientific landscape by fueling unprecedented advances in ana-lytical biochemistry-the 'omics revolution, which refers to the study of genes (genomics), transcripts (transcriptomics), proteins (proteo-mics) and the various metabolites (metabolomics). It is now possible to secure inventories of lipids, proteins, metabolites and RNA species in purified cell populations and to determine how these entities change in relation to cellular function.

  18. The probabilistic niche model reveals the niche structure and role of body size in a complex food web.

    Directory of Open Access Journals (Sweden)

    Richard J Williams

    Full Text Available The niche model has been widely used to model the structure of complex food webs, and yet the ecological meaning of the single niche dimension has not been explored. In the niche model, each species has three traits, niche position, diet position and feeding range. Here, a new probabilistic niche model, which allows the maximum likelihood set of trait values to be estimated for each species, is applied to the food web of the Benguela fishery. We also developed the allometric niche model, in which body size is used as the niche dimension. About 80% of the links in the empirical data are predicted by the probabilistic niche model, a significant improvement over recent models. As in the niche model, species are uniformly distributed on the niche axis. Feeding ranges are exponentially distributed, but diet positions are not uniformly distributed below the predator. Species traits are strongly correlated with body size, but the allometric niche model performs significantly worse than the probabilistic niche model. The best-fit parameter set provides a significantly better model of the structure of the Benguela food web than was previously available. The methodology allows the identification of a number of taxa that stand out as outliers either in the model's poor performance at predicting their predators or prey or in their parameter values. While important, body size alone does not explain the structure of the one-dimensional niche.

  19. Somatic cell nuclear transfer cloning: practical applications and current legislation.

    Science.gov (United States)

    Niemann, H; Lucas-Hahn, A

    2012-08-01

    Somatic cloning is emerging as a new biotechnology by which the opportunities arising from the advances in molecular genetics and genome analysis can be implemented in animal breeding. Significant improvements have been made in SCNT protocols in the past years which now allow to embarking on practical applications. The main areas of application of SCNT are: Reproductive cloning, therapeutic cloning and basic research. A great application potential of SCNT based cloning is the production of genetically modified (transgenic) animals. Somatic cell nuclear transfer based transgenic animal production has significant advances over the previously employed microinjection of foreign DNA into pronuclei of zygotes. This cell based transgenesis is compatible with gene targeting and allows both, the addition of a specific gene and the deletion of an endogenous gene. Efficient transgenic animal production provides numerous opportunities for agriculture and biomedicine. Regulatory agencies around the world have agreed that food derived from cloned animals and their offspring is safe and there is no scientific basis for questioning this. Commercial application of somatic cloning within the EU is via the Novel Food regulation EC No. 258/97. Somatic cloning raises novel questions regarding the ethical and moral status of animals and their welfare which has prompted a controversial discussion in Europe which has not yet been resolved.

  20. Ten Niche Strategies To Commercialize New High-Tech Products

    NARCIS (Netherlands)

    Ortt, J.R.; Langley, D.J.; Pals, N.

    2013-01-01

    There are serious gaps in the scientific literature relating to niche strategies as a means for commercializing new high-tech products. In particular, there is no clarity about what types of niche strategies can be distinguished, or how a niche strategy can be selected to suit a certain ituation. In

  1. Market positioning: the shifting effects of niche overlap

    NARCIS (Netherlands)

    Bruggeman, J.; Grunow, D.; Leenders, M.A.A.M.; Vermeulen, I.; Kuilman, J.G.

    2012-01-01

    Organizational ecology models of market dynamics emphasize the competition-inducing role of inter-organizational niche overlap—targeting similar market niches increases competitive pressure and thus reduces organizations’ fitness. Recent studies, however, have suggested that moderate niche overlap m

  2. Niching genetic algorithms for optimization in electromagnetics - I. Fundamentals

    OpenAIRE

    Sareni, Bruno; Krähenbühl, Laurent; Nicolas, Alain

    1998-01-01

    Niching methods extend genetic algorithms and permit the investigation of multiple optimal solutions in the search space. In this paper, we review and discuss various strategies of niching for optimization in electromagnetics. Traditional mathematical problems and an electromagnetic benchmark are solved using niching genetic algorithms to show their interest in real world optimization.

  3. Functional traits, convergent evolution, and periodic tables of niches.

    Science.gov (United States)

    Winemiller, Kirk O; Fitzgerald, Daniel B; Bower, Luke M; Pianka, Eric R

    2015-08-01

    Ecology is often said to lack general theories sufficiently predictive for applications. Here, we examine the concept of a periodic table of niches and feasibility of niche classification schemes from functional trait and performance data. Niche differences and their influence on ecological patterns and processes could be revealed effectively by first performing data reduction/ordination analyses separately on matrices of trait and performance data compiled according to logical associations with five basic niche 'dimensions', or aspects: habitat, life history, trophic, defence and metabolic. Resultant patterns then are integrated to produce interpretable niche gradients, ordinations and classifications. Degree of scheme periodicity would depend on degrees of niche conservatism and convergence causing species clustering across multiple niche dimensions. We analysed a sample data set containing trait and performance data to contrast two approaches for producing niche schemes: species ordination within niche gradient space, and niche categorisation according to trait-value thresholds. Creation of niche schemes useful for advancing ecological knowledge and its applications will depend on research that produces functional trait and performance datasets directly related to niche dimensions along with criteria for data standardisation and quality. As larger databases are compiled, opportunities will emerge to explore new methods for data reduction, ordination and classification.

  4. Closed-form expression for the current/ voltage characteristics of pin solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Taretto, K.; Rau, U.; Werner, J.H. [Institut fuer Physikalische Elektronik, Pfaffenwaldring 47, 70569, Stuttgart (Germany)

    2003-12-01

    A closed-form expression for the current-voltage relationship of pin diodes and pin solar cells is obtained. The model considers drift and diffusion currents, and assumes a uniform electric field in the intrinsic layer, equal diffusion lengths for electrons and holes and a homogeneous generation rate. We show that both drift and diffusion currents must be taken into account to describe the current over a wide range of applied voltage. The inclusion of both transport mechanisms results in diode ideality factors between 1.8 at low, and 1.2 at high applied voltages. Comparisons of current/voltage characteristics and solar cell output parameters obtained from our model with experimental data of thin-film silicon solar cells show that our model accurately explains the output characteristics of pin solar cells. (orig.)

  5. Ultra Low Voltage Class AB Switched Current Memory Cells Based on Floating Gate Transistors

    DEFF Research Database (Denmark)

    Mucha, Igor

    1999-01-01

    A proposal for a class AB switched current memory cell, suitable for ultra-low-voltage applications is presented. The proposal employs transistors with floating gates, allowing to build analog building blocks for ultralow supply voltage operation also in CMOS processes with high threshold voltages....... This paper presents the theoretical basis for the design of "floating-gate'' switched current memory cells by giving a detailed description and analysis of the most important impacts degrading the performance of the cells. To support the theoretical assumptions circuits based on "floating-gate'' switched...... current memory cells were designed using a CMOS process with threshold voltages V-T0n = \\V-T0p\\ = 0.9 V for the n- and p-channel devices. Both hand calculations and PSPICE simulations showed that the designed example switched current memory cell allowed a maximum signal range better than +/-18 mu...

  6. Population genetics and ecological niche of invasive Aedes albopictus in Mexico.

    Science.gov (United States)

    Pech-May, Angélica; Moo-Llanes, David A; Puerto-Avila, María Belem; Casas, Mauricio; Danis-Lozano, Rogelio; Ponce, Gustavo; Tun-Ku, Ezequiel; Pinto-Castillo, José Francisco; Villegas, Alejandro; Ibáñez-Piñon, Clemente R; González, Cassandra; Ramsey, Janine M

    2016-05-01

    The Asian tiger mosquito Aedes albopictus (Skuse), is one of the most invasive mosquito species worldwide. In Mexico it is now recorded in 12 states and represents a serious public health problem, given the recent introduction of Chikungunya on the southern border. The aim of this study was to analyze the population genetics of A. albopictus from all major recorded foci, and model its ecological niche. Niche similarity with that from its autochthonous distribution in Asia and other invaded countries were analyzed and its potential future expansion and potential human exposure in climate change scenarios measured. We analyzed 125 sequences of a 317 bp fragment of the cyt b gene from seven A. albopictus populations across Mexico. The samples belong to 25 haplotypes with moderate population structuring (Fst=0.081, pMexico. Both Neotropical and Nearctic regions are included in the Mexican niche model. Currently in Mexico, 38.6 million inhabitants are exposed to A. albopictus, which is expected to increase to 45.6 million by 2070. Genetic evidence supports collection information that A. albopictus was introduced to Mexico principally by land from the USA and Central and South America. Prevalent haplotypes from Mexico are shared with most invasive regions across the world, just as there was high niche similarity with both natural and invaded regions. The important overlap with the Asian niche model suggests a high potential for the species to disperse to sylvatic regions in Mexico.

  7. Incremental by Design? On the Role of Incumbents in Technology Niches

    DEFF Research Database (Denmark)

    Hain, Daniel S.; Jurowetzki, Roman

    endowment and experience enables them to stem large research projects and bring them all the way to the market. However, the involvement of incumbents might alter niche dynamics, making technology outcomes more incremental and adapted to the current unsustainable sociotechnical regime. The incumbents...

  8. Assessing niche development of Net Zero Energy Buildings (NZEBs) in India

    NARCIS (Netherlands)

    Jain, Mansi; Hoppe, Thomas; Bressers, Hans

    2015-01-01

    Large scale development of Net Zero Energy Buildings (NZEBs) is seen as a potential solution to deal with future energy challenges of the Indian building sector. This paper aims to assess the current status of NZEB niche development in India and identifies barriers that obstruct wide scale uptake of

  9. Voltage-dependent K+ currents contribute to heterogeneity of olfactory ensheathing cells

    Science.gov (United States)

    Rela, Lorena; Piantanida, Ana Paula; Bordey, Angelique; Greer, Charles A.

    2015-01-01

    The olfactory nerve is permissive for axon growth throughout life. This has been attributed in part to the olfactory ensheathing glial cells that encompass the olfactory sensory neuron fascicles. Olfactory ensheathing cells also promote axon growth in vitro and when transplanted in vivo to sites of injury. The mechanisms involved remain largely unidentified owing in part to the limited knowledge of the physiological properties of ensheathing cells. Glial cells rely for many functions on the properties of the potassium channels expressed; however, those expressed in ensheathing cells are unknown. Here we show that olfactory ensheathing cells express voltage-dependent potassium currents compatible with inward rectifier (Kir) and delayed rectifier (KDR) channels. Together with gap junction coupling, these contribute to the heterogeneity of membrane properties observed in olfactory ensheathing cells. The relevance of K+ currents expressed by ensheathing cells is discussed in relation to plasticity of the olfactory nerve. PMID:25856239

  10. Potassium currents in human myogenic cells from healthy and congenital myotonic dystrophy foetuses.

    Science.gov (United States)

    Nurowska, Ewa; Constanti, Andrew; Dworakowska, Beata; Mouly, Vincent; Furling, Denis; Lorenzon, Paola; Pietrangelo, Tiziana; Dołowy, Krzysztof; Ruzzier, Fabio

    2009-01-01

    The whole-cell patch clamp technique was used to record potassium currents in in vitro differentiating myoblasts isolated from healthy and myotonic dystrophy type 1 (DM1) foetuses carrying 2000 CTG repeats. The fusion of the DM1 myoblasts was reduced in comparison to that of the control cells. The dystrophic muscle cells expressed less voltage-activated K(+) (delayed rectifier and non-inactivating delayed rectifier) and inward rectifier channels than the age-matched control cells. However, the resting membrane potential was not significantly different between the control and the DM1 cells. After four days in a differentiation medium, the dystrophic cells expressed the fast-inactivating transient outward K(+) channels, which were not observed in healthy cells. We suggest that the low level of potassium currents measured in differentiated DM1 cells could be related to their impaired fusion.

  11. Current protocols in the generation of pluripotent stem cells: theoretical, methodological and clinical considerations

    Directory of Open Access Journals (Sweden)

    Brad B Swelstad

    2009-12-01

    Full Text Available Brad B Swelstad, Candace L KerrInstitute for Cell Engineering, Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, MA, USAAbstract: Pluripotent stem cells have been derived from various embryonic, fetal and adult sources. Embryonic stem cells (ESCs and parthenogenic ESCs (pESCs are derived from the embryo proper while embryonic germ cells (EGCs, embryonal carcinoma cells (ECCs, and germ-line stem cells (GSC are produced from germ cells. ECCs were the first pluripotent stem cell lines established from adult testicular tumors while EGCs are generated in vitro from primordial germ cells (PGCs isolated in late embryonic development. More recently, studies have also demonstrated the ability to produce GSCs from adult germ cells, known as spermatogonial stem cells. Unlike ECCs, the source of GSCs are normal, non-cancerous adult tissue. The study of these unique cell lines has provided information that has led to the ability to reprogram somatic cells into an ESC-like state. These cells, called induced pluripotent stem cells (iPSCs, have been derived from a number of human fetal and adult origins. With the promises pluripotent stem cells bring to cell-based therapies there remain several considerations that need to be carefully studied prior to their clinical use. Many of these issues involve understanding key factors regulating their generation, including those which define pluripotency. In this regard, the following article discusses critical aspects of pluripotent stem cell derivation and current issues about their therapeutic potential.Keywords: pluripotency, stem cells, derivation, human

  12. Move two: establishing a niche

    Directory of Open Access Journals (Sweden)

    Wasima Shehzad

    2008-04-01

    Full Text Available The significant purpose of the author in the Introduction of a research article is to convince the reader about the importance of the work to be presented. To achieve this end, a convincing “niche” needs to be built by evaluating, rejecting or indicating gaps in previous related work. The purpose of “establishing a niche” is to emphasize the current research project presented by the author. The present paper investigates how Computer scientists use this obligatory step of “Create a Research Space” (CARS model (Swales & Feak, 1994 & 2004 to highlight their own research work. This paper not only compares the results with other similar studies but also presents an in-depth analysis of various types of gap statements used in Computer Science research article Introductions. The issue of cyclicity of this step and the linguistic indicators used for the establishment of “niche” (the gap statements are both discussed.

  13. The use of climatic niches in screening procedures for introduced species to evaluate risk of spread: a case with the American Eastern grey squirrel.

    Science.gov (United States)

    Di Febbraro, Mirko; Lurz, Peter W W; Genovesi, Piero; Maiorano, Luigi; Girardello, Marco; Bertolino, Sandro

    2013-01-01

    Species introduction represents one of the most serious threats for biodiversity. The realized climatic niche of an invasive species can be used to predict its potential distribution in new areas, providing a basis for screening procedures in the compilation of black and white lists to prevent new introductions. We tested this assertion by modeling the realized climatic niche of the Eastern grey squirrel Sciurus carolinensis. Maxent was used to develop three models: one considering only records from the native range (NRM), a second including records from native and invasive range (NIRM), a third calibrated with invasive occurrences and projected in the native range (RCM). Niche conservatism was tested considering both a niche equivalency and a niche similarity test. NRM failed to predict suitable parts of the currently invaded range in Europe, while RCM underestimated the suitability in the native range. NIRM accurately predicted both the native and invasive range. The niche equivalency hypothesis was rejected due to a significant difference between the grey squirrel's niche in native and invasive ranges. The niche similarity test yielded no significant results. Our analyses support the hypothesis of a shift in the species' climatic niche in the area of introductions. Species Distribution Models (SDMs) appear to be a useful tool in the compilation of black lists, allowing identifying areas vulnerable to invasions. We advise caution in the use of SDMs based only on the native range of a species for the compilation of white lists for other geographic areas, due to the significant risk of underestimating its potential invasive range.

  14. Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells.

    Directory of Open Access Journals (Sweden)

    Keun-A Chang

    Full Text Available The use of non-chemical methods to differentiate stem cells has attracted researchers from multiple disciplines, including the engineering and the biomedical fields. No doubt, growth factor based methods are still the most dominant of achieving some level of proliferation and differentiation control--however, chemical based methods are still limited by the quality, source, and amount of the utilized reagents. Well-defined non-chemical methods to differentiate stem cells allow stem cell scientists to control stem cell biology by precisely administering the pre-defined parameters, whether they are structural cues, substrate stiffness, or in the form of current flow. We have developed a culture system that allows normal stem cell growth and the option of applying continuous and defined levels of electric current to alter the cell biology of growing cells. This biphasic current stimulator chip employing ITO electrodes generates both positive and negative currents in the same culture chamber without affecting surface chemistry. We found that biphasic electrical currents (BECs significantly increased the proliferation of fetal neural stem cells (NSCs. Furthermore, BECs also promoted the differentiation of fetal NSCs into neuronal cells, as assessed using immunocytochemistry. Our results clearly show that BECs promote both the proliferation and neuronal differentiation of fetal NSCs. It may apply to the development of strategies that employ NSCs in the treatment of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases.

  15. Potassium currents in human myogenic cells from donors of different ages.

    Science.gov (United States)

    Nurowska, Ewa; Dworakowska, Beata; Kloch, Monika; Sobol, Maria; Dołowy, Krzysztof; Wernig, Anton; Ruzzier, Fabio

    2006-06-01

    Ageing in humans is accompanied by a reduction in the capacity of satellite cells to proliferate and the forming myoblasts to fuse. The processes of myoblast differentiation and fusion are associated with specific changes in the cells electrical properties. We wanted to elucidate the possible effects of ageing on these parameters and performed whole-cell patch-clamp recordings on human myoblasts obtained from biopsies of skeletal muscles from 2-, 48- and 76-year-old donors. First, we found that resting membrane potential on the 4th day of differentiation in vitro is less negative in the older than in the younger cells. Moreover, the oldest cells showed a smaller density of outward and inward potassium currents. More cells from the old and middle-age donors have a low (less than -40 mV) potential of activation for the outward potassium current. We conclude that in human myoblasts biophysical properties of potassium currents change with donor age.

  16. Diabetes treatment: A rapid review of the current and future scope of stem cell research

    OpenAIRE

    Sheik Abdulazeez, Sheriff

    2013-01-01

    Diabetes mellitus is a major health concern of the developing and developed nations across the globe. This devastating disease accounts for the 5% deaths around the world annually. The current treatment methods do not address the underlying causes of the disease and have severe limitations. Stem cells are unique cells with the potential to differentiate into any type of specialized cells. This feature of both adult and embryonic stem cells was explored in great detail by the scientists around...

  17. Study of the Logistics Enterprise Development Path based on Niche Theory

    Institute of Scientific and Technical Information of China (English)

    Sun Wenxia

    2013-01-01

    This paper refers evolutionary ecology of niche theory,analyzes logistics enterprises niche,as well as niche overlapping,niche separation,niche compression,niche expansionetc.And on this basis,this paper proposes,the development path of the logistics enterprise “co-operation,with in the horizontal,external vertical cooperation”,hoping advancing further of logisticsenterprises.

  18. Identificação do nicho de progenitores mesenquimais no fígado de embriões e fetos caninos: uma fonte de células-tronco para terapia celular Identification of mesenchymal progenitor niches from liver of embryo and fetuses of canines: a source of stem cells for cell therapy

    Directory of Open Access Journals (Sweden)

    Daniele S. Martins

    2012-12-01

    potential. This organ during the fetal period in mammals acts as a transient hematopoietic niche, being the main organ responsible for hematopoiesis in the fetus, and contribute to the formation of permanent niche in the adult bone marrow, thus can be considered a niche for mesenchymal stem cells (MSC and parents. However, little is known about the location of these cells in FF, so the present study aims to identify the niche of mesenchymal progenitors in FF and dogs in order to contribute to the techniques of cell isolation and extraction. Together was performed to verify the expression of the transcription factor Oct-3/4 of the protein and DNA polymerase delta (PCNA. For the analysis of five embryos were used and 11 canine fetuses with gestational ages ranging from 25-60 days. The results elucidated from 25 days of gestation showed the FF is bulky and composed of all the typical structures, among them the portal triad, bile ducts and hepatic artery branches. With 30 days of gestation were identified the first requirements of mesenchymal progenitors (MP at 60 days while the niches were completely formed with location similar to adult liver (AL. However, cells immunoreactives for Oct-3/4 were not identified, therefore, point out that the FL is a source of PM, presenting as an alternative for therapeutic purposes as well as for studying the developmental biology of MSC and parents.

  19. The pharmacological properties of K+ currents from rabbit isolated aortic smooth muscle cells.

    OpenAIRE

    Halliday, F. C.; Aaronson, P. I.; Evans, A. M.; Gurney, A M

    1995-01-01

    1. Using the whole-cell patch-clamp technique, the effects of several K+ channel blocking drugs on K+ current recorded from rabbit isolated aortic smooth muscle cells were investigated. 2. Upon depolarization from -80 mV, outward K+ current composed of several distinct components were observed: a transient, 4-aminopyridine (4-AP)-sensitive component (I1) and a sustained component (Isus), comprising a 4-AP-sensitive delayed rectifier current (IK(V)), and a noisy current which was sensitive to ...

  20. Stem cell sources for tooth regeneration: current status and future prospects.

    Science.gov (United States)

    Otsu, Keishi; Kumakami-Sakano, Mika; Fujiwara, Naoki; Kikuchi, Kazuko; Keller, Laetitia; Lesot, Hervé; Harada, Hidemitsu

    2014-01-01

    Stem cells are capable of renewing themselves through cell division and have the remarkable ability to differentiate into many different types of cells. They therefore have the potential to become a central tool in regenerative medicine. During the last decade, advances in tissue engineering and stem cell-based tooth regeneration have provided realistic and attractive means of replacing lost or damaged teeth. Investigation of embryonic and adult (tissue) stem cells as potential cell sources for tooth regeneration has led to many promising results. However, technical and ethical issues have hindered the availability of these cells for clinical application. The recent discovery of induced pluripotent stem (iPS) cells has provided the possibility to revolutionize the field of regenerative medicine (dentistry) by offering the option of autologous transplantation. In this article, we review the current progress in the field of stem cell-based tooth regeneration and discuss the possibility of using iPS cells for this purpose.

  1. Stem cell sources for tooth regeneration: current status and future prospects

    Directory of Open Access Journals (Sweden)

    Keishi eOtsu

    2014-02-01

    Full Text Available Stem cells are capable of renewing themselves through cell division and have the remarkable ability to differentiate into many different types of cells. They therefore have the potential to become a central tool in regenerative medicine. During the last decade, advances in tissue engineering and stem cell-based tooth regeneration have provided realistic and attractive means of replacing lost or damaged teeth. Investigation of embryonic and adult (tissue stem cells as potential cell sources for tooth regeneration has led to many promising results. However, technical and ethical issues have hindered the availability of these cells for clinical application. The recent discovery of induced pluripotent stem (iPS cells has provided the possibility to revolutionize the field of regenerative medicine (dentistry by offering the option of autologous transplantation. In this article, we review the current progress in the field of stem cell-based tooth regeneration and discuss the possibility of using iPS cells for this purpose.

  2. Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Vladislav Volarevic

    2014-01-01

    Full Text Available Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

  3. Evidence of niche shift and global invasion potential of the Tawny Crazy ant, Nylanderia fulva.

    Science.gov (United States)

    Kumar, Sunil; LeBrun, Edward G; Stohlgren, Thomas J; Stabach, Jared A; McDonald, Danny L; Oi, David H; LaPolla, John S

    2015-10-01

    Analysis of an invasive species' niche shift between native and introduced ranges, along with potential distribution maps, can provide valuable information about its invasive potential. The tawny crazy ant, Nylanderia fulva, is a rapidly emerging and economically important invasive species in the southern United States. It is originally from east-central South America and has also invaded Colombia and the Caribbean Islands. Our objectives were to generate a global potential distribution map for N. fulva, identify important climatic drivers associated with its current distribution, and test whether N. fulva's realized climatic niche has shifted across its invasive range. We used MaxEnt niche model to map the potential distribution of N. fulva using its native and invaded range occurrences and climatic variables. We used principal component analysis methods for investigating potential shifts in the realized climatic niche of N. fulva during invasion. We found strong evidence for a shift in the realized climatic niche of N. fulva across its invasive range. Our models predicted potentially suitable habitat for N. fulva in the United States and other parts of the world. Our analyses suggest that the majority of observed occurrences of N. fulva in the United States represent stabilizing populations. Mean diurnal range in temperature, degree days at ≥10°C, and precipitation of driest quarter were the most important variables associated with N. fulva distribution. The climatic niche expansion demonstrated in our study may suggest significant plasticity in the ability of N. fulva to survive in areas with diverse temperature ranges shown by its tolerance for environmental conditions in the southern United States, Caribbean Islands, and Colombia. The risk maps produced in this study can be useful in preventing N. fulva's future spread, and in managing and monitoring currently infested areas.

  4. Doctoral education in a successful ecological niche

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh; Lund, Ole

    2014-01-01

    explore the microclimate in an ecological niche of doctoral education. Based on a theoretical definition of microclimate as the emotional atmosphere that ties group members together and affects their actions, we conducted a case study that aimed to describe the key features of the microclimate...... in a successful ecological niche of doctoral education, and the ways in which the microclimate support the doctoral students’ learning. The methods we applied in the case study were based on short-term ethnographic fieldwork. The results reveal four key features of the emotional atmosphere in the microclimate...... successful doctoral education because it: 1) fleshes out the professional attitude that is necessary for becoming a successful researcher in the department, 2) shapes and adapts the doctoral students’ desires to grasp and identify with the department’s practices, and 3) provides the doctoral students...

  5. [Niche comparison of dominant entomopathogenic fungi in three forest ecosystems].

    Science.gov (United States)

    Chen, Ming-Jun; Huang, Bo; Li, Zeng-Zhi

    2011-05-01

    An investigation was made on the quantitative composition, niche width, and niche overlap of dominant entomopathogenic fungi in three different forest ecosystems, i.e., natural broad-leaved forest, natural secondary broad-leaved forest, and pure Masson' s pine plantation. In the three forest ecosystems, Beauveria bassiana was the first dominant species in natural secondary broad-leaved forest, the second in pure Masson's pine plantation, and the third in natural broad-leaved forest. B. bassiana had the broadest temporal niche width and nutritional niche width, whereas the dominant species Isaria cateinannulata, L. farinose, and I. tenuipes had much smaller niche widths. Meanwhile, B. bassiana had larger temporal niche overlaps but smaller nutritional niche overlaps with other dominant entomopathogenic fungi. It was suggested that in the three forest ecosystems, B. bassiana had the longest occurrence duration, widest host range, and strongest environmental adaptability.

  6. Evolution of lactase persistence: an example of human niche construction.

    Science.gov (United States)

    Gerbault, Pascale; Liebert, Anke; Itan, Yuval; Powell, Adam; Currat, Mathias; Burger, Joachim; Swallow, Dallas M; Thomas, Mark G

    2011-03-27

    Niche construction is the process by which organisms construct important components of their local environment in ways that introduce novel selection pressures. Lactase persistence is one of the clearest examples of niche construction in humans. Lactase is the enzyme responsible for the digestion of the milk sugar lactose and its production decreases after the weaning phase in most mammals, including most humans. Some humans, however, continue to produce lactase throughout adulthood, a trait known as lactase persistence. In European populations, a single mutation (-13910*T) explains the distribution of the phenotype, whereas several mutations are associated with it in Africa and the Middle East. Current estimates for the age of lactase persistence-associated alleles bracket those for the origins of animal domestication and the culturally transmitted practice of dairying. We report new data on the distribution of -13910*T and summarize genetic studies on the diversity of lactase persistence worldwide. We review relevant archaeological data and describe three simulation studies that have shed light on the evolution of this trait in Europe. These studies illustrate how genetic and archaeological information can be integrated to bring new insights to the origins and spread of lactase persistence. Finally, we discuss possible improvements to these models.

  7. Niche Markets: Filling Gaps with Expertise, Ingenuity.

    Science.gov (United States)

    Kaldy, Joanne

    2015-08-01

    Niche markets present opportunities for pharmacists to expand their presence and increase the demand for their services. These practitioners have clinical skills that they can use to improve medication management, reduce medication-related problems and hospitalizations, and enhance the quality of life for patients in specialty areas such as menopause management and women's health, hospice and palliative care, and pediatric long-term care.

  8. Current protocols in the generation of pluripotent stem cells: theoretical, methodological and clinical considerations.

    Science.gov (United States)

    Swelstad, Brad B; Kerr, Candace L

    2009-12-22

    Pluripotent stem cells have been derived from various embryonic, fetal and adult sources. Embryonic stem cells (ESCs) and parthenogenic ESCs (pESCs) are derived from the embryo proper while embryonic germ cells (EGCs), embryonal carcinoma cells (ECCs), and germ-line stem cells (GSC) are produced from germ cells. ECCs were the first pluripotent stem cell lines established from adult testicular tumors while EGCs are generated in vitro from primordial germ cells (PGCs) isolated in late embryonic development. More recently, studies have also demonstrated the ability to produce GSCs from adult germ cells, known as spermatogonial stem cells. Unlike ECCs, the source of GSCs are normal, non-cancerous adult tissue. The study of these unique cell lines has provided information that has led to the ability to reprogram somatic cells into an ESC-like state. These cells, called induced pluripotent stem cells (iPSCs), have been derived from a number of human fetal and adult origins. With the promises pluripotent stem cells bring to cell-based therapies there remain several considerations that need to be carefully studied prior to their clinical use. Many of these issues involve understanding key factors regulating their generation, including those which define pluripotency. In this regard, the following article discusses critical aspects of pluripotent stem cell derivation and current issues about their therapeutic potential.

  9. Chemotransduction in the Carotid Body: K+ Current Modulated by Po2 in Type I Chemoreceptor Cells

    Science.gov (United States)

    Lopez-Barneo, Jose; Lopez-Lopez, Jose R.; Urena, Juan; Gonzalez, Constancio

    1988-07-01

    The ionic currents of carotid body type I cells and their possible involvement in the detection of oxygen tension (Po2) in arterial blood are unknown. The electrical properties of these cells were studied with the whole-cell patch clamp technique, and the hypothesis that ionic conductances can be altered by changes in Po2 was tested. The results show that type I cells have voltage-dependent sodium, calcium, and potassium channels. Sodium and calcium currents were unaffected by a decrease in Po2 from 150 to 10 millimeters of mercury, whereas, with the same experimental protocol, potassium currents were reversibly reduced by 25 to 50 percent. The effect of hypoxia was independent of internal adenosine triphosphate and calcium. Thus, ionic conductances, and particularly the O2-sensitive potassium current, play a key role in the transduction mechanism of arterial chemoreceptors.

  10. Balance Trees Reveal Microbial Niche Differentiation.

    Science.gov (United States)

    Morton, James T; Sanders, Jon; Quinn, Robert A; McDonald, Daniel; Gonzalez, Antonio; Vázquez-Baeza, Yoshiki; Navas-Molina, Jose A; Song, Se Jin; Metcalf, Jessica L; Hyde, Embriette R; Lladser, Manuel; Dorrestein, Pieter C; Knight, Rob

    2017-01-01

    Advances in sequencing technologies have enabled novel insights into microbial niche differentiation, from analyzing environmental samples to understanding human diseases and informing dietary studies. However, identifying the microbial taxa that differentiate these samples can be challenging. These issues stem from the compositional nature of 16S rRNA gene data (or, more generally, taxon or functional gene data); the changes in the relative abundance of one taxon influence the apparent abundances of the others. Here we acknowledge that inferring properties of individual bacteria is a difficult problem and instead introduce the concept of balances to infer meaningful properties of subcommunities, rather than properties of individual species. We show that balances can yield insights about niche differentiation across multiple microbial environments, including soil environments and lung sputum. These techniques have the potential to reshape how we carry out future ecological analyses aimed at revealing differences in relative taxonomic abundances across different samples. IMPORTANCE By explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss. Author Video: An author video summary of this article is available.

  11. Balance Trees Reveal Microbial Niche Differentiation

    Science.gov (United States)

    Morton, James T.; Sanders, Jon; Quinn, Robert A.; McDonald, Daniel; Gonzalez, Antonio; Vázquez-Baeza, Yoshiki; Navas-Molina, Jose A.; Metcalf, Jessica L.; Hyde, Embriette R.; Lladser, Manuel; Dorrestein, Pieter C.

    2017-01-01

    ABSTRACT Advances in sequencing technologies have enabled novel insights into microbial niche differentiation, from analyzing environmental samples to understanding human diseases and informing dietary studies. However, identifying the microbial taxa that differentiate these samples can be challenging. These issues stem from the compositional nature of 16S rRNA gene data (or, more generally, taxon or functional gene data); the changes in the relative abundance of one taxon influence the apparent abundances of the others. Here we acknowledge that inferring properties of individual bacteria is a difficult problem and instead introduce the concept of balances to infer meaningful properties of subcommunities, rather than properties of individual species. We show that balances can yield insights about niche differentiation across multiple microbial environments, including soil environments and lung sputum. These techniques have the potential to reshape how we carry out future ecological analyses aimed at revealing differences in relative taxonomic abundances across different samples. IMPORTANCE By explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss. Author Video: An author video summary of this article is available. PMID:28144630

  12. Stem cells for liver tissue repair:Current knowledge and perspectives

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Stem cells from extra- or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated.Therefore,they are being increasingly considered for future applications in liver cell therapy.In that field,liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation,while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures.However,the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype,both in vitro and in vivo.Furthermore,the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures.The present review focuses on the current knowledge of the stern cell potential for liver therapy.We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo.We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

  13. A mathematical model of the current density distribution in electrochemical cells - AUTHORS’ REVIEW

    Directory of Open Access Journals (Sweden)

    PREDRAG M. ŽIVKOVIĆ

    2011-06-01

    Full Text Available An approach based on the equations of electrochemical kinetics for the estimation of the current density distribution in electrochemical cells is presented. This approach was employed for a theoretical explanation of the phenomena of the edge and corner effects. The effects of the geometry of the system, the kinetic parameters of the cathode reactions and the resistivity of the solution are also discussed. A procedure for a complete analysis of the current distribution in electrochemical cells is presented.

  14. Pulsed Direct Current Electric Fields Enhance Osteogenesis in Adipose-Derived Stromal Cells

    OpenAIRE

    Hammerick, Kyle E.; James, Aaron W.; Huang, Zubin; Prinz, Fritz B.; Michael T. Longaker

    2009-01-01

    Adipose-derived stromal cells (ASCs) constitute a promising source of cells for regenerative medicine applications. Previous studies of osteogenic potential in ASCs have focused on chemicals, growth factors, and mechanical stimuli. Citing the demonstrated role electric fields play in enhancing healing in bone fractures and defects, we investigated the ability of pulsed direct current electric fields to drive osteogenic differentiation in mouse ASCs. Employing 50 Hz direct current electric fie...

  15. Effect of Direct Electric Current on the Cell Surface Properties of Phenol-Degrading Bacteria

    OpenAIRE

    Luo, Qishi; Wang, Hui; Zhang, Xihui; Qian, Yi

    2005-01-01

    The change in cell surface properties in the presence of electric currents is of critical concern when the potential to manipulate bacterial movement with electric fields is evaluated. In this study, the effects of different direct electric currents on the cell surface properties involved in bacterial adhesion were investigated by using a mixed phenol-degrading bacterial culture in the exponential growth phase. The traits investigated were surface hydrophobicity (measured by adherence to n-oc...

  16. Numerical study on short-circuit current of single layer organic solar cells with Schottkey contacts

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The influence of the cathode work function,carriers mobilities and temperature on the short-circuit current of single layer organic solar cells with Schottkey contacts was numerically studied,and the quantitative dependences of the short-circuit current on these quantities were obtained.The results provide the theoretical foundation for experimental study of single layer organic solar cells with Schottkey contacts.

  17. Extracellular stimulation of nerve cells with electric current spikes induced by voltage steps

    OpenAIRE

    2016-01-01

    A new stimulation paradigm is presented for the stimulation of nerve cells by extracellular electric currents. In the new paradigm stimulation is achieved with the current spike induced by a voltage step whenever the voltage step is applied to a live biological tissue. By experimental evidence and theoretical arguments, it is shown that this spike is well suited for the stimulation of nerve cells. Stimulation of the human tongue is used for proof of principle. Charge injection thresholds are ...

  18. Corneal stem cells and tissue engineering: Current advances and future perspectives.

    Science.gov (United States)

    de Araujo, Aline Lütz; Gomes, José Álvaro Pereira

    2015-06-26

    Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there are many challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

  19. Development of a Direct Methanol Fuel Cell with Lightweight Disc Type Current Collectors

    Directory of Open Access Journals (Sweden)

    Yean-Der Kuan

    2014-05-01

    Full Text Available The direct methanol fuel cell (DMFC adopts methanol solution as a fuel suitable for low power portable applications. A miniature, lightweight, passive air-breathing design is therefore desired. This paper presents a novel planar disc-type DMFC with multiple cells containing a novel developed lightweight current collector at both the anode and cathode sides. The present lightweight current collector adopts FR4 Glass/Epoxy as the substrate with the current collecting areas located at the corresponding membrane electrolyte assembly (MEA areas. The current collecting areas are fabricated by sequentially coating a corrosion resistant layer and electrical conduction layer via the thermal evaporation technique. The anode current collector has carved flow channels for fuel transport and production. The cathode current collector has drilled holes for passive air breathing. In order to ensure feasibility in the present concept a 3-cell prototype DMFC module with lightweight disc type current collectors is designed and constructed. Experiments were conducted to measure the cell performance. The results show that the highest cell power output is 54.88 mW·cm−2 and successfully demonstrate the feasibility of this novel design.

  20. Two outward potassium current types are expressed during the neural differentiation of neural stem cells**

    Institute of Scientific and Technical Information of China (English)

    Ruiying Bai; Guowei Gao; Ying Xing; Hong Xue

    2013-01-01

    The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S + G2/M phase was high. However, the ratio of cells in the S + G2/M phase decreased obviously as differentiation proceeded. Whole-cellpatch-clamp re-cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo-campus could be cultured and induced to differentiate into functional neurons under defined condi-tions in vitro. The differentiated neurons expressed two types of outward potassium ion currents similar to those of mature neurons in vivo.

  1. Application of isothermal current deep level transient spectroscopy to solar cells

    Science.gov (United States)

    Rancour, D. P.; Pierret, R. F.; Lundstrom, M. S.; Melloch, M. R.

    1989-03-01

    The utility of isothermal current deep level transient spectroscopy (DLTS) techniques in directly probing solar cells is described and illustrated. A modified approach to processing the isothermal DLTS data is also presented. Specifically, it is pointed out that properly normalized isothermal data, whether derived from a current or capacitance transient, should conform to a single, temperature-independent curve.

  2. Stem cells for clinical use in cardiovascular medicine: current limitations and future perspectives.

    Science.gov (United States)

    Menasché, Philippe

    2005-10-01

    Cell transplantation is currently gaining a growing interest as a potential new means of improving the prognosis of patients with cardiac failure. The basic assumption is that left ventricular dysfunction is largely due to the loss of a critical number of cardiomyocytes and that it can be partly reversed by implantation of new contractile cells into the postinfarction scars. Primarily for practical reasons, autologous skeletal myoblasts have been the first to undergo clinical trials and now that the feasibility of the procedure is well established, efficacy data are expected from the ongoing randomized studies. Bone marrow stem cells are also generating a great deal of interest, particularly in patients with acute myocardial infarction, and are currently undergoing extensive clinical testing although recent data have raised a cautionary note about the transdifferentiation potential of these cells. While experimental studies and early-phase clinical trials tend to support the concept that cell therapy may enhance cardiac repair, several key issues still need to be addressed including (1) the optimal type of donor cells in relation to the clinical profile of the patients, (2) the mechanism by which cell engraftment improves cardiac function, (3) the optimization of cell survival, (4) the development of less invasive cell delivery techniques and (5) the potential benefits of cell transplantation in nonischemic heart failure. Current evidence suggests, however, that adult stem cells (myogenic or marrow-derived) fail to electromechanically integrate within the recipient heart, thereby mandating the search for second generation cell types able to achieve this goal which is the prerequisite for an effective enhancement of contractile function. Preliminary data suggest that cells that feature a true cardiomyogenic phenotype such as cardiac stem cells and cardiac-precommitted embryonic stem cells may fall in this category and carry the potential for ensuring a true

  3. Current concepts of hair cell differentiation and planar cell polarity in inner ear sensory organs.

    Science.gov (United States)

    Sienknecht, Ulrike J

    2015-07-01

    Phylogenetically and ontogenetically, vertebrate development led to the generation of several inner ear sensory organs. During embryogenesis, cell fate specification determines whether each progenitor cell differentiates into a sensory hair cell or a supporting cell within the common sensory primordium. Finally, all sensory epithelia of the inner ear consist of a hair cell/supporting cell mosaic, albeit with anatomical differences depending on the sensory organ type. Hair cells develop a polarized bundle of stereovilli that is of functional importance for mechanotransduction. After initiating stereovillar development, hair cells align their bundles in a coordinated fashion, generating a characteristic hair cell orientation pattern, a process referred to as planar cell polarity (PCP). The pathway that controls PCP in the inner ear needs both to establish the development of a polarized morphology of the stereovillar bundle of the hair cell and to organize a systematic hair cell alignment. Because the hair cell orientation patterns of the various inner ear organs and vertebrate species differ fundamentally, it becomes apparent that in vertebrates, different aspects of PCP need to be independently controlled. In spite of important progress recently gained in the field of PCP research, we still need to identify the mechanisms (1) that initiate molecular asymmetries in cells, (2) that guide the transmission of polarity information from cell to cell, and (3) that consistently translate such polarity information into morphological asymmetries of hair cells.

  4. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2012

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Chandler, Kevin [Battelle, Columbus, OH (United States); Gikakis, Christina [Federal Transit Administration, Washington, DC (United States)

    2012-11-01

    This report is the sixth in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The report also provides a snapshot of current FCEB performance results over the last year.

  5. On the surface recombination current of metal-insulator semiconductor inversion layer solar cells

    DEFF Research Database (Denmark)

    Nielsen, Otto M.

    1981-01-01

    voltages Voc were found to be lower than for ~ cells. The measured differences in Voc were higher than expected from the dark characteristics which is explained as a difference in the surface recombination current due to a higher interface state density Nss of ~ cells. Journal of Applied Physics...

  6. Degradation of Solid Oxide Electrolysis Cells Operated at High Current Densities

    DEFF Research Database (Denmark)

    Tao, Youkun; Ebbesen, Sune Dalgaard; Mogensen, Mogens Bjerg

    2014-01-01

    In this work the durability of solid oxide cells for co-electrolysis of steam and carbon dioxide (45 % H2O + 45 % CO2 + 10 % H2) at high current densities was investigated. The tested cells are Ni-YSZ electrode supported, with a YSZ electrolyte and either a LSM-YSZ or LSCF-CGO oxygen electrode...

  7. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2013

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Gikakis, C.

    2013-12-01

    This report is the seventh in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The report also provides a snapshot of current FCEB performance results from August 2012 through July 2013 for five FCEB demonstrations at four transit agencies.

  8. AM-1 short circuit currents in small area PIN a-SiH(x) solar cells

    Science.gov (United States)

    Weinberger, B. R.; Deckman, H. W.; Wronski, C. R.; Witzke, H.

    The potential pitfalls which may lead to an overestimation of AM-1 short-circuit current densities have been investigated for 0.02 sq cm a-SiH(x) solar cell structures. The investigators have spatially profiled carrier collection in a-Si PIN solar cells, using a scanned 10 micron diameter laser beam. The small beam size yields not only microscopic information about carrier collection efficiency spectra, but permits study of carrier collection at high light intensity without significantly heating the cell. Laser scans at low illumination levels were employed to determine the true active area of PIN solar cells, and these are compared to cell collection efficiency spectra.

  9. Potassium currents in type II vestibular hair cells isolated from the guinea-pig's crista ampullaris.

    Science.gov (United States)

    Griguer, C; Kros, C J; Sans, A; Lehouelleur, J

    1993-11-01

    Type II vestibular hair cells were isolated from cristae ampullares of guinea-pig and maintained in vitro for 2-3 h. Outward membrane currents were studied under whole-cell voltage-clamp conditions. Type II hair cells had resting potentials of about -45 mV. Depolarizing voltage steps from a holding potential of -80 or -90 mV induced time- and voltage-dependent outward currents which slowly decayed to a sustained level. Tail currents reversed at about -70 mV, indicating that the outward currents were mainly carried by potassium ions. The currents had an activation threshold around -50 mV. The transient component was completely removed by a depolarizing pre-pulse positive to -10 mV. While bath application of 4-aminopyridine (5 mM) reduced both components, extracellular tetraethylammonium (10 mM) or zero calcium preferentially diminished the sustained current. We conclude that at least two potassium conductances are present, a delayed rectifier with a relatively fast inactivation and a calcium-dependent potassium current. Depolarizing current injections induced an electrical resonance in the voltage responses, with a frequency of 25-100 Hz, larger currents causing higher frequencies.

  10. Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

    Science.gov (United States)

    Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

    2017-02-01

    Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords.NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a

  11. Evolution of pollination niches in a generalist plant clade.

    Science.gov (United States)

    Gómez, José María; Perfectti, Francisco; Abdelaziz, Mohamed; Lorite, Juan; Muñoz-Pajares, Antonio Jesús; Valverde, Javier

    2015-01-01

    It is widely assumed that floral diversification occurs by adaptive shifts between pollination niches. In contrast to specialized flowers, identifying pollination niches of generalist flowers is a challenge. Consequently, how generalist pollination niches evolve is largely unknown. We apply tools from network theory and comparative methods to investigate the evolution of pollination niches among generalist species belonging to the genus Erysimum. These species have similar flowers. We found that the studied species may be grouped in several multidimensional niches separated not by a shift of pollinators, but instead by quantitative variation in the relative abundance of pollinator functional groups. These pollination niches did not vary in generalization degree; we did not find any evolutionary trend toward specialization within the studied clade. Furthermore, the evolution of pollination niche fitted to a Brownian motion model without phylogenetic signal, and was characterized by frequent events of niche convergences and divergences. We presume that the evolution of Erysimum pollination niches has occurred mostly by recurrent shifts between slightly different generalized pollinator assemblages varying spatially as a mosaic and without any change in specialization degree. Most changes in pollination niches do not prompt floral divergence, a reason why adaptation to pollinators is uncommon in generalist plants.

  12. Current-voltage characteristics of bulk heterojunction organic solar cells: connection between light and dark curves

    Energy Technology Data Exchange (ETDEWEB)

    Boix, Pablo P.; Guerrero, Antonio; Garcia-Belmonte, Germa; Bisquert, Juan [Photovoltaic and Optoelectronic Devices Group, Departament de Fisica, Universitat Jaume I, ES-12071 Castello (Spain); Marchesi, Luis F. [Laboratorio Interdisciplinar de, Eletroquimica e Ceramica (LIEC), Universidade Federal de Sao Carlos (Brazil); Photovoltaic and Optoelectronic Devices Group, Departament de Fisica, Universitat Jaume I, ES-12071 Castello (Spain)

    2011-11-15

    A connection is established between recombination and series resistances extracted from impedance spectroscopy and current-voltage curves of polythiophene:fullerene organic solar cells. Recombination is shown to depend exclusively on the (Fermi level) voltage, which allows construction of the current-voltage characteristics in any required conditions based on a restricted set of measurements. The analysis highlights carrier recombination current as the determining mechanism of organic solar cell performance. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. A New High-Speed Low Distortion Switched-Current Cell

    DEFF Research Database (Denmark)

    Shah, Peter Jivan; Toumazou, Christofer

    1996-01-01

    A new switched-current cell is presented which simultaneously offers high speed, low distortion, low gain error, and a virtual ground input. In a simulation example 0.01% distortion was achieved at 50MHz sampling rate which makes the cell very well suited for high accuracy high speed filtering...... applications. It is outlined how the cell can be used in FIR filtering and to form integrators with high DC gain and low distortion....

  14. A Metabolic Biofuel Cell: Conversion of Human Leukocyte Metabolic Activity to Electrical Currents

    Directory of Open Access Journals (Sweden)

    Cui X Tracy

    2011-05-01

    Full Text Available Abstract An investigation of the electrochemical activity of human white blood cells (WBC for biofuel cell (BFC applications is described. WBCs isolated from whole human blood were suspended in PBS and introduced into the anode compartment of a proton exchange membrane (PEM fuel cell. The cathode compartment contained a 50 mM potassium ferricyanide solution. Average current densities between 0.9 and 1.6 μA cm-2 and open circuit potentials (Voc between 83 and 102 mV were obtained, which were both higher than control values. Cyclic voltammetry was used to investigate the electrochemical activity of the activated WBCs in an attempt to elucidate the mechanism of electron transfer between the cells and electrode. Voltammograms were obtained for the WBCs, including peripheral blood mononuclear cells (PBMCs - a lymphocyte-monocyte mixture isolated on a Ficoll gradient, a B lymphoblastoid cell line (BLCL, and two leukemia cell lines, namely K562 and Jurkat. An oxidation peak at about 363 mV vs. SCE for the PMA (phorbol ester activated primary cells, with a notable absence of a reduction peak was observed. Oxidation peaks were not observed for the BLCL, K562 or Jurkat cell lines. HPLC confirmed the release of serotonin (5-HT from the PMA activated primary cells. It is believed that serotonin, among other biochemical species released by the activated cells, contributes to the observed BFC currents.

  15. Stem cell therapy for Alzheimer's disease and related disorders: current status and future perspectives.

    Science.gov (United States)

    Tong, Leslie M; Fong, Helen; Huang, Yadong

    2015-03-13

    Underlying cognitive declines in Alzheimer's disease (AD) are the result of neuron and neuronal process losses due to a wide range of factors. To date, all efforts to develop therapies that target specific AD-related pathways have failed in late-stage human trials. As a result, an emerging consensus in the field is that treatment of AD patients with currently available drug candidates might come too late, likely as a result of significant neuronal loss in the brain. In this regard, cell-replacement therapies, such as human embryonic stem cell- or induced pluripotent stem cell-derived neural cells, hold potential for treating AD patients. With the advent of stem cell technologies and the ability to transform these cells into different types of central nervous system neurons and glial cells, some success in stem cell therapy has been reported in animal models of AD. However, many more steps remain before stem cell therapies will be clinically feasible for AD and related disorders in humans. In this review, we will discuss current research advances in AD pathogenesis and stem cell technologies; additionally, the potential challenges and strategies for using cell-based therapies for AD and related disorders will be discussed.

  16. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    Directory of Open Access Journals (Sweden)

    Alison Gartland

    2016-09-01

    Full Text Available Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

  17. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    DEFF Research Database (Denmark)

    Gartland, Alison; Erler, Janine Terra; Cox, Thomas Robert

    2016-01-01

    and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview......Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating...... of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis....

  18. Neuropeptide FF receptor modulates potassium currents in a dorsal root ganglion cell line.

    Science.gov (United States)

    Mollereau, Catherine; Roumy, Michel; Zajac, Jean-Marie

    2011-01-01

    This study investigated the presence of neuropeptide FF (NPFF) receptors on F-11 cells, a hybridoma derived from rat dorsal root ganglia (DRG) and mouse neuroblastoma. Binding experiments revealed a low density (4 fmol/mg) of high affinity (0.5 nM) [(3)H]-EYF binding sites in these cells. The whole-cell planar patch-clamp technique showed that dNPA, a selective NPFF(2) agonist, increased the voltage-dependent potassium outward currents (about 30 pA/pF) by 21%; this reversible effect on sustained delayed potassium currents is blocked by tetraethylammonium. The similar effects of NPFF and opioid agonists on K(+) currents in this cell line may explain their similar antinociceptive actions at the spinal level.

  19. Electrolytic/fuel cell bundles and systems including a current collector in communication with an electrode thereof

    Science.gov (United States)

    Hawkes, Grant L.; Herring, James S.; Stoots, Carl M.; O& #x27; Brien, James E.

    2013-03-05

    Electrolytic/fuel cell bundles and systems including such bundles include an electrically conductive current collector in communication with an anode or a cathode of each of a plurality of cells. A cross-sectional area of the current collector may vary in a direction generally parallel to a general direction of current flow through the current collector. The current collector may include a porous monolithic structure. At least one cell of the plurality of cells may include a current collector that surrounds an outer electrode of the cell and has at least six substantially planar exterior surfaces. The planar surfaces may extend along a length of the cell, and may abut against a substantially planar surface of a current collector of an adjacent cell. Methods for generating electricity and for performing electrolysis include flowing current through a conductive current collector having a varying cross-sectional area.

  20. The Morphological and Molecular Changes of Brain Cells Exposed to Direct Current Electric Field Stimulation

    Science.gov (United States)

    Pelletier, Simon J.; Lagacé, Marie; St-Amour, Isabelle; Arsenault, Dany; Cisbani, Giulia; Chabrat, Audrey; Fecteau, Shirley; Lévesque, Martin

    2015-01-01

    Background: The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Methods: Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. Results: In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. Conclusion: We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field. PMID:25522422

  1. Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology

    Science.gov (United States)

    Der Sarkissian, Shant; Lévesque, Thierry; Noiseux, Nicolas

    2017-01-01

    Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the post-ischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring

  2. A rapidly inactivating Ca2(+)-dependent K+ current in pheochromocytoma cells (PC12) of the rat.

    Science.gov (United States)

    Pun, R Y; Behbehani, M M

    1990-01-01

    The membrane electrical properties of undifferentiated pheochromocytoma cells of the rat (PC12) were studied using both current- and voltage-clamp techniques with the use of low-resistance blunt-tipped micropipettes (patch electrodes). In the presence of tetrodotoxin (TTX, 2-3 microM), a spike-like wave form with a prominent after-hyperpolarization (AHP) was recorded following brief (less than 10 ms) depolarizing current pulses. The inorganic divalent cations, Cd2+ (0.5 mM), Mn2+ (4 mM), and 0 mM Ca2+/4 mM Mg2+ solution prolonged the duration, attenuated the AHP, slowed the rate of repolarization, and slightly enhanced the amplitude of this wave form. A rapidly inactivating outward current was recorded in over 70% of the cells under voltage-clamp conditions. This transient current was elicited at about -30 mV, and was blocked by tetraethylammonium (5 mM), inorganic divalent cations (Cd2+, 0.5 mM; Mn2+, 4 mM; Ba2+, 3 mM), and removal of Ca2+ (0 mM Ca2+/4 mM Mg2+) from the local perfusion medium. In addition, 4-aminopyridine (5 mM), which blocks the transient outward K+ current IA in a variety of excitable cells, did not have any appreciable effect on this rapidly inactivating current. Moreover, it was possible to elicit the current at a holding potential of -40 mV. The reversal potential of this current was -90 mV, and shifted positively when extracellular K+ concentrations were elevated. It is concluded that PC12 cells have a rapidly inactivating Ca2(+)-dependent K+ current. A possible explanation for the transient nature of this current may be the presence of an effective intracellular Ca2+ buffering (uptake or extrusion) system.

  3. Analysis of leakage current in GaAs micro-solar cell arrays

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The output characteristics of micro-solar cell arrays are analyzed on the basis of a modified model in which the shunt resistance between cell lines results in current leakage.The modification mainly consists of adding a shunt resistor network to the traditional model.The obtained results agree well with the reported experimental results.The calculation results demonstrate that leakage current in substrate affects seriously the performance of GaAs micro-solar cell arrays.The performance of arrays can be improved by reducing the number of cells per line.In addition,at a certain level of integration,an appropriate space occupancy rate of the single cell is recommended for ensuring high open circuit voltages,and it is more appropriate to set the rates at 80%-90% through the calculation.

  4. Nanoscale bio-platforms for living cell interrogation: current status and future perspectives

    Science.gov (United States)

    Chang, Lingqian; Hu, Jiaming; Chen, Feng; Chen, Zhou; Shi, Junfeng; Yang, Zhaogang; Li, Yiwen; Lee, Ly James

    2016-02-01

    The living cell is a complex entity that dynamically responds to both intracellular and extracellular environments. Extensive efforts have been devoted to the understanding intracellular functions orchestrated with mRNAs and proteins in investigation of the fate of a single-cell, including proliferation, apoptosis, motility, differentiation and mutations. The rapid development of modern cellular analysis techniques (e.g. PCR, western blotting, immunochemistry, etc.) offers new opportunities in quantitative analysis of RNA/protein expression up to a single cell level. The recent entries of nanoscale platforms that include kinds of methodologies with high spatial and temporal resolution have been widely employed to probe the living cells. In this tutorial review paper, we give insight into background introduction and technical innovation of currently reported nanoscale platforms for living cell interrogation. These highlighted technologies are documented in details within four categories, including nano-biosensors for label-free detection of living cells, nanodevices for living cell probing by intracellular marker delivery, high-throughput platforms towards clinical current, and the progress of microscopic imaging platforms for cell/tissue tracking in vitro and in vivo. Perspectives for system improvement were also discussed to solve the limitations remains in current techniques, for the purpose of clinical use in future.

  5. Nanoscale bio-platforms for living cell interrogation: current status and future perspectives.

    Science.gov (United States)

    Chang, Lingqian; Hu, Jiaming; Chen, Feng; Chen, Zhou; Shi, Junfeng; Yang, Zhaogang; Li, Yiwen; Lee, Ly James

    2016-02-14

    The living cell is a complex entity that dynamically responds to both intracellular and extracellular environments. Extensive efforts have been devoted to the understanding intracellular functions orchestrated with mRNAs and proteins in investigation of the fate of a single-cell, including proliferation, apoptosis, motility, differentiation and mutations. The rapid development of modern cellular analysis techniques (e.g. PCR, western blotting, immunochemistry, etc.) offers new opportunities in quantitative analysis of RNA/protein expression up to a single cell level. The recent entries of nanoscale platforms that include kinds of methodologies with high spatial and temporal resolution have been widely employed to probe the living cells. In this tutorial review paper, we give insight into background introduction and technical innovation of currently reported nanoscale platforms for living cell interrogation. These highlighted technologies are documented in details within four categories, including nano-biosensors for label-free detection of living cells, nanodevices for living cell probing by intracellular marker delivery, high-throughput platforms towards clinical current, and the progress of microscopic imaging platforms for cell/tissue tracking in vitro and in vivo. Perspectives for system improvement were also discussed to solve the limitations remains in current techniques, for the purpose of clinical use in future.

  6. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities

    Directory of Open Access Journals (Sweden)

    Liangfu Jiang

    2017-01-01

    Full Text Available Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration.

  7. Niche Genetic Algorithm with Accurate Optimization Performance

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-hua; YAN De-kun

    2005-01-01

    Based on crowding mechanism, a novel niche genetic algorithm was proposed which can record evolutionary direction dynamically during evolution. After evolution, the solutions's precision can be greatly improved by means of the local searching along the recorded direction. Simulation shows that this algorithm can not only keep population diversity but also find accurate solutions. Although using this method has to take more time compared with the standard GA, it is really worth applying to some cases that have to meet a demand for high solution precision.

  8. Current Approach in Surface Plasmons for Thin Film and Wire Array Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Keya Zhou

    2015-07-01

    Full Text Available Surface plasmons, which exist along the interface of a metal and a dielectric, have been proposed as an efficient alternative method for light trapping in solar cells during the past ten years. With unique properties such as superior light scattering, optical trapping, guide mode coupling, near field concentration, and hot-electron generation, metallic nanoparticles or nanostructures can be tailored to a certain geometric design to enhance solar cell conversion efficiency and to reduce the material costs. In this article, we review current approaches on different kinds of solar cells, such as crystalline silicon (c-Si and amorphous silicon (a-Si thin film solar cells, organic solar cells, nanowire array solar cells, and single nanowire solar cells.

  9. Experimental and numerical studies of local current mapping on a PEM fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Hwnag, J.J. [Department of Environment and Energy, National University of Tainan, Tainan 700 (China); Chang, W.R. [Department of Landscape Architecture, Chung-Hua University, Hsinchu 300 (China); Peng, R.G. [Department of Mechanical Engineering, National Chiao Tong University, Hsinchu 300 (China); Chen, P.Y. [Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 300 (China); Su, A. [Department of Mechanical Engineering and Fuel Cell Center, Yuan Ze University, Taoyuan (China)

    2008-10-15

    Local current distribution on a PEM fuel cell has been mapped experimentally by using a special-designed single cell fixture. It is composed of a composite cathodic flow-field plate, a membrane electrode assembly (MEA) and a stainless-steel anodic flow-field plate. An array of 16 individual conductive segments was distributed on the composite plate. A self-made MEA is in direct contact with the segmented current collectors. Regional-averaged current through each segment is determined by using the Hall-effect sensor. To ensure the data reliability, a comparison of polarization curves was made between the composite flow-field plate and the conventional flow-field plate. Then, the effects of flow-field patterns, dew points of the cathodic feedings and cathodic stoichiometrics on the local current distribution were examined. The transient variation of the local current distribution on the cathode under supersaturated conditions was further visualized to illustrate the flooding phenomena in different flow patterns. This technique developed by the present work has contributed to knowledge and understanding the local current distributions in a PEM fuel cell that is helpful in designing the fuel-cell components. (author)

  10. Sodium and calcium currents shape action potentials in immature mouse inner hair cells.

    Science.gov (United States)

    Marcotti, Walter; Johnson, Stuart L; Rusch, Alfons; Kros, Corne J

    2003-11-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at -71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.

  11. Beyond climate: disturbance niche shifts in invasive species

    OpenAIRE

    González-Moreno, Pablo; Diez, Jeffrey M.; Richardson, David M.; Vilà, Montserrat

    2015-01-01

    Analysing how species niches shift between native and introduced ranges is a powerful tool for understanding the determinants of species distributions and for anticipating range expansions by invasive species. Most studies only consider the climatic niche, by correlating widely available presence-only data with regional climate. However, habitat characteristics and disturbance also shape species niches, thereby potentially confounding shifts attributed only to differences in climate. Here we ...

  12. Central nervous system myeloid cells as drug targets: current status and translational challenges.

    Science.gov (United States)

    Biber, Knut; Möller, Thomas; Boddeke, Erik; Prinz, Marco

    2016-02-01

    Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic.

  13. The Niche Hiker's Guide to Population Ecology : A logical reconstruction of organization ecology's niche theory

    NARCIS (Netherlands)

    Peli, G; Raftery, AE

    1997-01-01

    Logical formalization is a formal method for the analysis of theoretical arguments in the social sciences. Hannan and Freeman's organizational niche theory (1989) is rebuilt by means of First-Order Logic, and its predictions are derived as theorems. Translation into a formal language makes the theor

  14. Ecological niche transferability using invasive species as a case study.

    Directory of Open Access Journals (Sweden)

    Miguel Fernández

    Full Text Available Species distribution modeling is widely applied to predict invasive species distributions and species range shifts under climate change. Accurate predictions depend upon meeting the assumption that ecological niches are conserved, i.e., spatially or temporally transferable. Here we present a multi-taxon comparative analysis of niche conservatism using biological invasion events well documented in natural history museum collections. Our goal is to assess spatial transferability of the climatic niche of a range of noxious terrestrial invasive species using two complementary approaches. First we compare species' native versus invasive ranges in environmental space using two distinct methods, Principal Components Analysis and Mahalanobis distance. Second we compare species' native versus invaded ranges in geographic space as estimated using the species distribution modeling technique Maxent and the comparative index Hellinger's I. We find that species exhibit a range of responses, from almost complete transferability, in which the invaded niches completely overlap with the native niches, to a complete dissociation between native and invaded ranges. Intermediate responses included expansion of dimension attributable to either temperature or precipitation derived variables, as well as niche expansion in multiple dimensions. We conclude that the ecological niche in the native range is generally a poor predictor of invaded range and, by analogy, the ecological niche may be a poor predictor of range shifts under climate change. We suggest that assessing dimensions of niche transferability prior to standard species distribution modeling may improve the understanding of species' dynamics in the invaded range.

  15. Ecological niche modeling and its applications in biodiversity conservation

    Directory of Open Access Journals (Sweden)

    Gengping Zhu

    2013-01-01

    Full Text Available Based on the environmental variables that associated with species’ occurrence records, ecological niche modeling (ENM seeks to characterize environmental conditions suitable for a particular species and then identify where suitable environmental habitats are distributed in the space. Recently, ENM has been used increasingly in biological invasion, conservation biology, biological responses toclimate change, disease spatial transmission, and variety aspects of ecology and evolutionary biology research. However, the theoretical background of these applications is generally poorly understood, leading to artifactual conclusions in some studies (e.g. niche differentiation during species’ invasion. In this paper we discuss the relationship between niche and geographic distribution and introduce the theoretical basis of ENM, along with relationships between the niche and ENM. Abiotic/biotic, historical and dispersal factors are three key elements that determine species’ geographic distributions at different scales. By using environmental variables derived from distributional records, ENM is based on observations that already include effects of biotic interactions, therefore ENM is used to characterize somewhere between the realized niche and potential niche, not the fundamental niche. Grinnellian and Eltonian niches are both manifested in ENM calibration, depending on the types of variables used to fit model, the natural spatial scale at which they can be measured, and the dispersal of individuals throughout the environment. Applications of ENM in understanding ecological requirements of species, discovery of new species or populations, nature reserve design, predicting potential invasion, modeling biological responses to climate change, niche conservatism, and pecies delimitation are discussed in this paper.

  16. Evolution of climatic niche specialization: a phylogenetic analysis in amphibians.

    Science.gov (United States)

    Bonetti, Maria Fernanda; Wiens, John J

    2014-11-22

    The evolution of climatic niche specialization has important implications for many topics in ecology, evolution and conservation. The climatic niche reflects the set of temperature and precipitation conditions where a species can occur. Thus, specialization to a limited set of climatic conditions can be important for understanding patterns of biogeography, species richness, community structure, allopatric speciation, spread of invasive species and responses to climate change. Nevertheless, the factors that determine climatic niche width (level of specialization) remain poorly explored. Here, we test whether species that occur in more extreme climates are more highly specialized for those conditions, and whether there are trade-offs between niche widths on different climatic niche axes (e.g. do species that tolerate a broad range of temperatures tolerate only a limited range of precipitation regimes?). We test these hypotheses in amphibians, using phylogenetic comparative methods and global-scale datasets, including 2712 species with both climatic and phylogenetic data. Our results do not support either hypothesis. Rather than finding narrower niches in more extreme environments, niches tend to be narrower on one end of a climatic gradient but wider on the other. We also find that temperature and precipitation niche breadths are positively related, rather than showing trade-offs. Finally, our results suggest that most amphibian species occur in relatively warm and dry environments and have relatively narrow climatic niche widths on both of these axes. Thus, they may be especially imperilled by anthropogenic climate change.

  17. Current perspectives on natural killer cell education and tolerance: emerging roles for inhibitory receptors

    Directory of Open Access Journals (Sweden)

    Thomas LM

    2015-03-01

    Full Text Available L Michael Thomas Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA Abstract: Natural killer (NK cells are regulated through the coordinated functions of activating and inhibitory receptors. These receptors can act during the initial engagement of an NK cell with a target cell, or in subsequent NK cell engagements to maintain tolerance. Notably, each individual possesses a sizable minority-population of NK cells that are devoid of inhibitory receptors that recognize the surrounding MHC class I (ie, self-MHC. Since these NK cells cannot perform conventional inhibition, they are rendered less responsive through the process of NK cell education (also known as licensing in order to reduce the likelihood of auto-reactivity. This review will delineate current views on NK cell education, clarify various misconceptions about NK cell education, and, lastly, discuss the relevance of NK cell education in anti-cancer therapies. Keywords: natural killer cell education, natural killer cell inhibitory receptors, immunotherapy, cancer

  18. Microstructure characterisation of solid oxide electrolysis cells operated at high current density

    DEFF Research Database (Denmark)

    Bowen, Jacob R.; Bentzen, Janet Jonna; Chen, Ming;

    High temperature solid oxide cells can be operated either as fuel cells or electrolysis cells for efficient power generation or production of hydrogen from steam or synthesis gas (H2 + CO) from steam and CO2 respectively. When operated under harsh conditions, they often exhibit microstructural......, microstructure evolution of the Ni-yttria stabilized zirconia (YSZ) is followed as a function of galvanostatic steam electrolysis testing at current densities between -0.5 and -1.0 A cm-2 for periods of up to 750 hours at 800 °C. The volume fraction and size of the percolating Ni particles was statistically...... quantified using the mean linear intercept method as a function of current density and correlated to increases in serial resistance. The above structural changes are then compared in terms of electrode degradation observed during the co-electrolysis of steam and CO2 at current densities up to -1.5 A cm-2...

  19. Master Equation Approach to Current-Voltage Characteristics of Solar Cells

    Science.gov (United States)

    Oh, Sangchul; Zhang, Yiteng; Alharbi, Fahhad; Kais, Sabre

    2015-03-01

    The current-voltage characteristics of solar cells is obtained using quantum master equations for electrons, holes, and excitons, in which generation, recombination, and transport processes are taken into account. As a first example, we simulate a photocell with a molecular aggregate donor to investigate whether a delocalized quantum state could enhance the efficiency. As a second example, we calculate the current-voltage characteristics of conventional p-n junction solar cells and perovskite solar cells using the master equation. The connection between the drift-diffusion model and the master equation method is established. The short-circuit current and the open-circuit voltage are calculated numerically as a function of the intensity of the sunlight and material properties such as energy gaps, diffusion constants, etc.

  20. Ryanodine prolongs Ca-currents while suppressing contraction in rat ventricular muscle cells.

    OpenAIRE

    Mitchell, M. R.; Powell, T; Terrar, D. A.; Twist, V. W.

    1984-01-01

    Ryanodine (1 microM) suppressed or abolished contraction in response to step depolarization in voltage-clamped cells isolated from adult rat ventricular myocardium. The step depolarizations evoked the second inward current, which is carried largely by Ca ions under these conditions, and there was little or no change in the amplitude of this current when contraction was reduced or abolished by ryanodine. The effects of ryanodine on contraction were, however, accompanied by a prolongation of th...

  1. Current progress and future perspectives for organic/inorganic perovskite solar cells

    Directory of Open Access Journals (Sweden)

    Pablo P. Boix

    2014-01-01

    Full Text Available The recent emergence of efficient solar cells based on organic/inorganic lead halide perovskite absorbers promises to transform the fields of dye-sensitized, organic, and thin film solar cells. Solution processed photovoltaics incorporating perovskite absorbers have achieved efficiencies of 15% [1] in solid-state device configurations, superseding liquid dye sensitized solar cell (DSC, evaporated and tandem organic solar cells, as well as various thin film photovoltaics; thus establishing perovskite solar cells as a robust candidate for commercialization. Since the first reports in late 2012, interest has soared in the innovative device structures as well as new materials, promising further improvements. However, identifying the basic working mechanisms, which are still being debated, will be crucial to design the optimum device configuration and maximize solar cell efficiencies. Here we distill the current state-of-the-art and highlight the guidelines to ascertain the scientific challenges as well as the requisites to make this technology market-viable.

  2. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2011

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.; Gikakis, C.

    2011-11-01

    This status report, fifth in a series of annual status reports from the U.S. Department of Energy's National Renewable Energy Laboratory (NREL), discusses the achievements and challenges of fuel cell propulsion for transit and summarizes the introduction of fuel cell transit buses in the United States. Progress this year includes an increase in the number of fuel cell electric buses (FCEBs), from 15 to 25, operating at eight transit agencies, as well as increased diversity of the fuel cell design options for transit buses. The report also provides an analysis of the combined results from fuel cell transit bus demonstrations evaluated by NREL with a focus on the most recent data through July 2011 including fuel cell power system reliability and durability; fuel economy; roadcall; and hydrogen fueling results. These evaluations cover 22 of the 25 FCEBs currently operating.

  3. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies.

    Science.gov (United States)

    Wang, S Z; Rui, Y F; Lu, J; Wang, C

    2014-10-01

    Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

  4. Current applications of adipose-derived stem cells and their future perspectives.

    Science.gov (United States)

    Kim, Eun-Hee; Heo, Chan Yeong

    2014-01-26

    Adult stem cells have a great potential to treat various diseases. For these cell-based therapies, adipose-derived stem cells (ADSCs) are one of the most promising stem cell types, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs and iPSCs have taken center stage due to their pluripotency. However, ESCs and iPSCs have limitations in ethical issues and in identification of characteristics, respectively. Unlike ESCs and iPSCs, ADSCs do not have such limitations and are not only easily obtained but also uniquely expandable. ADSCs can differentiate into adipocytes, osteoblasts, chondrocytes, myocytes and neurons under specific differentiation conditions, and these kinds of differentiation potential of ADSCs could be applied in regenerative medicine e.g., skin reconstruction, bone and cartilage formation, etc. In this review, the current status of ADSC isolation, differentiation and their therapeutic applications are discussed.

  5. Calcium Transient and Sodium-Calcium Exchange Current in Human versus Rabbit Sinoatrial Node Pacemaker Cells

    OpenAIRE

    Verkerk, Arie O.; Marcel M. G. J. van Borren; Ronald Wilders

    2013-01-01

    There is an ongoing debate on the mechanism underlying the pacemaker activity of sinoatrial node (SAN) cells, focusing on the relative importance of the “membrane clock” and the “Ca2+ clock” in the generation of the small net membrane current that depolarizes the cell towards the action potential threshold. Specifically, the debate centers around the question whether the membrane clock-driven hyperpolarization-activated current, I f , which is also known as the “funny current” or “pacemaker c...

  6. On Calculating the Current-Voltage Characteristic of Multi-Diode Models for Organic Solar Cells

    CERN Document Server

    Roberts, Ken

    2016-01-01

    We provide an alternative formulation of the exact calculation of the current-voltage characteristic of solar cells which have been modeled with a lumped parameters equivalent circuit with one or two diodes. Such models, for instance, are suitable for describing organic solar cells whose current-voltage characteristic curve has an inflection point, also known as an S-shaped anomaly. Our formulation avoids the risk of numerical overflow in the calculation. It is suitable for implementation in Fortran, C or on micro-controllers.

  7. Effect of decreasing electrical resistance in Characeae cell membranes caused by the flow of alternating current

    Directory of Open Access Journals (Sweden)

    Edward Śpiewla

    2014-02-01

    Full Text Available By means of the techniques of external electrodes and microelectrodes, it was found that evanescent flow of an alternating current through plasmalemma of Characeae cells neutralises oscillatory change in their electrical resistance and reversibly diminishes its value. This effect is particularly significant in the case of "high resistance cells", but it weakens with increasing temperature. The value of the estimated activation energy indicates that, after flow of the alternating current through the membrane, a rapid increase in the conductivity may be caused by an increase in conductivity of potassium channels. This result seems to support the hypothesis of electroconformational feedback.

  8. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

    Directory of Open Access Journals (Sweden)

    Marc Amoyel

    2016-01-01

    Full Text Available The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs, which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs, which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.

  9. Solar cell evaluation using electron beam induced current with the large chamber scanning electron microscope

    Science.gov (United States)

    Wink, Tara; Kintzel, Edward; Marienhoff, Peter; Klein, Martin

    2012-02-01

    An initial study using electron beam induced current (EBIC) to evaluate solar cells has been carried out with the large chamber scanning electron microscope (LC-SEM) at the Western Kentucky University Nondestructive Analysis Center. EBIC is a scanning electron microscope technique used for the characterization of semiconductors. To facilitate our studies, we developed a Solar Amplification System (SASY) for analyzing current distribution and defects within a solar cell module. Preliminary qualitative results will be shown for a solar cell module that demonstrates the viability of the technique using the LC-SEM. Quantitative EBIC experiments will be carried out to analyze defects and minority carrier properties. Additionally, a well-focused spot of light from an LED mounted at the side of the SEM column will scan the same area of the solar cell using the LC-SEM positioning system. SASY will then output the solar efficiency to be compared with the minority carrier properties found using EBIC.

  10. Cell-balancing currents in parallel strings of a battery system

    Science.gov (United States)

    Dubarry, Matthieu; Devie, Arnaud; Liaw, Bor Yann

    2016-07-01

    Lithium-ion batteries are attractive for vehicle electrification or grid modernization applications. In these applications, battery packs are required to have multiple-cell configurations and battery management system to operate properly and safely. Here, a useful equivalent circuit model was developed to simulate the spontaneous transient balancing currents among parallel strings in a battery system. The simulation results were validated with experimental data to illustrate the accuracy and validity of the model predictions. Understanding the transient behavior of such cell and string balancing in a parallel circuit configuration is very important to assess the impacts of current fluctuation and cell variability on a battery system's performance, regarding durability, reliability, safety, abuse tolerance and failure prevention, including possible short circuit or open circuit conditions. Additional features and advantages, including the ability to assessing impacts on the performance of the string assemblies from string swapping or cell/module replacement in the strings, could be realized to aid battery management, maintenance and repair.

  11. Thermal niche estimators and the capability of poor dispersal species to cope with climate change

    Science.gov (United States)

    Sánchez-Fernández, David; Rizzo, Valeria; Cieslak, Alexandra; Faille, Arnaud; Fresneda, Javier; Ribera, Ignacio

    2016-03-01

    For management strategies in the context of global warming, accurate predictions of species response are mandatory. However, to date most predictions are based on niche (bioclimatic) models that usually overlook biotic interactions, behavioral adjustments or adaptive evolution, and assume that species can disperse freely without constraints. The deep subterranean environment minimises these uncertainties, as it is simple, homogeneous and with constant environmental conditions. It is thus an ideal model system to study the effect of global change in species with poor dispersal capabilities. We assess the potential fate of a lineage of troglobitic beetles under global change predictions using different approaches to estimate their thermal niche: bioclimatic models, rates of thermal niche change estimated from a molecular phylogeny, and data from physiological studies. Using bioclimatic models, at most 60% of the species were predicted to have suitable conditions in 2080. Considering the rates of thermal niche change did not improve this prediction. However, physiological data suggest that subterranean species have a broad thermal tolerance, allowing them to stand temperatures never experienced through their evolutionary history. These results stress the need of experimental approaches to assess the capability of poor dispersal species to cope with temperatures outside those they currently experience.

  12. Lateral current effects on the voltage distribution in the emitter of solar cells under concentrated sunlight

    Energy Technology Data Exchange (ETDEWEB)

    Morales-Acevedo, Arturo [CINVESTAV-IPN, Electrical Engineering Department, Avenida IPN No. 2508, 07360 Mexico, DF (Mexico)

    2009-04-15

    The design of the grid contact in silicon solar cells is one of the most important steps for the optimization and fabrication of these energy conversion devices. The voltage drop due to the lateral flow of current towards the grid fingers can be a limiting factor causing the reduction of conversion efficiency. For low current levels this voltage drop can be made small, for typical values of sheet resistance in the emitter, but for solar cells made to operate at high sun concentrations this efficiency loss can be important, unless there is a clear vision of the current and voltage distribution so that the emitter and grid design can be improved. Hence, it is important to establish and solve the current and voltage distribution equations for solar cells with a grid contact. In this work, first these equations are established and then they are solved in order to show the effects that the lateral current flow in the emitter cause on the voltage distribution, particularly at high illumination levels. In addition, it will be shown that the open circuit voltage is significantly reduced due to the lateral current flow as compared to the value predicted from a simple equivalent circuit with a lumped resistance model. (author)

  13. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2012

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chander, K.; Gikakis, C.

    2012-11-01

    This report is the sixth in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The report also provides a snapshot of current FCEB performance results over the last year. There are 25 active FCEBs in demonstrations this year at eight locations.

  14. Analytical Model for Voltage-Dependent Photo and Dark Currents in Bulk Heterojunction Organic Solar Cells

    OpenAIRE

    2016-01-01

    A physics-based explicit mathematical model for the external voltage-dependent forward dark current in bulk heterojunction (BHJ) organic solar cells is developed by considering Shockley-Read-Hall (SRH) recombination and solving the continuity equations for both electrons and holes. An analytical model for the external voltage-dependent photocurrent in BHJ organic solar cells is also proposed by incorporating exponential photon absorption, dissociation efficiency of bound electron-hole pairs (...

  15. Characteristics of chloride currents activated by noradrenaline in rabbit ear artery cells.

    Science.gov (United States)

    Amédée, T; Large, W A; Wang, Q

    1990-09-01

    1. Responses to noradrenaline were studied in isolated rabbit ear artery cells with the nystatin method of whole-cell patch-clamp recording. With this technique it was possible to obtain reproducible responses to noradrenaline which was not possible with traditional whole-cell recording. 2. With NaCl as the major constituent of the bathing solution (potassium-free pipette and external solutions) the reversal potential (Er) of the noradrenaline-evoked current was about 0 mV. When external chloride was replaced by thiocyanate, iodide, nitrate and bromide, Er was shifted to more negative potentials which indicates that a chloride conductance increase contributes to the current activated by noradrenaline. 3. When sodium was substituted by Tris, N-methyl-D-glucamine, choline or barium, Er of the noradrenaline-evoked current did not alter. This result suggests that a cation conductance is not implicated in the response to noradrenaline recorded with the nystatin method of whole-cell recording. 4. The chloride current activated by noradrenaline was blocked by the selective alpha 1-adrenoceptor antagonist prazosin but was not affected by the alpha 2-adrenoceptor antagonist yohimbine. 5. When cells were exposed to zero calcium bathing solutions the amplitude of the current elicited by noradrenaline was unaffected when measured within 1-2 min in zero calcium conditions. Continued exposure to 0 Ca + 1 mM-EGTA solution reversibly abolished the chloride current to noradrenaline. 6. In the presence of caffeine, which releases Ca2+ from internal stores and itself induced an inward current (at a holding potential of -50 mV), noradrenaline did not elicit a current. These data suggest that the chloride current evoked by noradrenaline results from an increase in intracellular concentration of calcium derived from internal stores. 7. The chloride channel blocking agents 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS; 0.5 mM) and furosemide (0.5 mM) produced partial