WorldWideScience

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. Hepatic stem cell niches

    OpenAIRE

    Kordes, Claus; Häussinger, Dieter

    2013-01-01

    Stem cell niches are special microenvironments that maintain stem cells and control their behavior to ensure tissue homeostasis and regeneration throughout life. The liver has a high regenerative capacity that involves stem/progenitor cells when the proliferation of hepatocytes is impaired. In recent years progress has been made in the identification of potential hepatic stem cell niches. There is evidence that hepatic progenitor cells can originate from niches in the canals...

  3. Artificial Stem Cell Niches

    OpenAIRE

    Lutolf, Matthias P.; Blau, Helen M.

    2009-01-01

    Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-...

  4. Niche construction game cancer cells play*

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2016-01-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  5. Niche construction game cancer cells play

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  6. 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.

  7. Adhesion in the stem cell niche: biological roles and regulation

    OpenAIRE

    Chen, Shuyi; Lewallen, Michelle; Xie, Ting

    2013-01-01

    Stem cell self-renewal is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles for adhe...

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

    OpenAIRE

    Ningning He; Lu Zhang; Jian Cui; Zongjin Li

    2014-01-01

    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 rev...

  9. The Cell as the First Niche Construction.

    Science.gov (United States)

    Torday, John S

    2016-01-01

    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. PMID:27136594

  10. 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.

  11. 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.

  12. 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

  13. Mimicking Stem Cell Niches to Increase Stem Cell Expansion

    OpenAIRE

    Dellatore, Shara M.; Garcia, A. Sofia; Miller, William M.

    2008-01-01

    Niches regulate lineage-specific stem cell self-renewal vs. differentiation in vivo and are comprised of supportive cells and extracellular matrix components arranged in a 3-dimensional topography of controlled stiffness in the presence of oxygen and growth factor gradients. Mimicking stem cell niches in a defined manner will facilitate production of the large numbers of stem cells needed to realize the promise of regenerative medicine and gene therapy. Progress has been made in mimicking com...

  14. Niche

    OpenAIRE

    O'Donovan, Danielle

    2001-01-01

    Capital of middle niche/sedilia of south nave wall, moulding from top down comprises: chamfer, fillet, hollow, stiff-leaf foliage, bell, necking roll-and-fillet. Here again Early English characteristics are manifest but the niche may date from the later middle ages.

  15. A stem cell niche dominance theorem

    Directory of Open Access Journals (Sweden)

    Shibata Darryl K

    2011-01-01

    Full Text Available Abstract Background Multilevelness is a defining characteristic of complex systems. For example, in the intestinal tissue the epithelial lining is organized into crypts that are maintained by a niche of stem cells. The behavior of the system 'as a whole' is considered to emerge from the functioning and interactions of its parts. What we are seeking here is a conceptual framework to demonstrate how the "fate" of intestinal crypts is an emergent property that inherently arises from the complex yet robust underlying biology of stem cells. Results We establish a conceptual framework in which to formalize cross-level principles in the context of tissue organization. To this end we provide a definition for stemness, which is the propensity of a cell lineage to contribute to a tissue fate. We do not consider stemness a property of a cell but link it to the process in which a cell lineage contributes towards tissue (malfunction. We furthermore show that the only logically feasible relationship between the stemness of cell lineages and the emergent fate of their tissue, which satisfies the given criteria, is one of dominance from a particular lineage. Conclusions The dominance theorem, conceived and proven in this paper, provides support for the concepts of niche succession and monoclonal conversion in intestinal crypts as bottom-up relations, while crypt fission is postulated to be a top-down principle.

  16. 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.

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

    International Nuclear Information System (INIS)

    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

  18. 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 ].

  19. Niche

    OpenAIRE

    O'Donovan, Danielle

    2001-01-01

    Arch and hood moulding of westernmost niche of south nave wall. Arch moulding from inner surface comprises: chamfer, flat surface, hollow, roll-and-fillet, roll, hollow, chamfer, flat surface of wall. The hood, from outside face to inner comprises: roll-and-fillet, hollow, chamfer. The style of this moulding can best be described as debased Early English. The roll-and-fillet is particularly deformed.

  20. 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.

  1. Stem cell autotomy and niche interaction in different systems

    OpenAIRE

    Dorn, David C.; Dorn, August

    2015-01-01

    The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form ...

  2. Stem cell autotomy and niche interaction in different systems.

    Science.gov (United States)

    Dorn, David C; Dorn, August

    2015-07-26

    The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells (homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche (hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion (E-cadherin) and the direction of asymmetrical GSC division - as they were found in Drosophila - can hardly be translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon

  3. 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

  4. Stochastic dynamics of interacting haematopoietic stem cell niche lineages.

    Directory of Open Access Journals (Sweden)

    Tamás Székely

    2014-09-01

    Full Text Available Since we still know very little about stem cells in their natural environment, it is useful to explore their dynamics through modelling and simulation, as well as experimentally. Most models of stem cell systems are based on deterministic differential equations that ignore the natural heterogeneity of stem cell populations. This is not appropriate at the level of individual cells and niches, when randomness is more likely to affect dynamics. In this paper, we introduce a fast stochastic method for simulating a metapopulation of stem cell niche lineages, that is, many sub-populations that together form a heterogeneous metapopulation, over time. By selecting the common limiting timestep, our method ensures that the entire metapopulation is simulated synchronously. This is important, as it allows us to introduce interactions between separate niche lineages, which would otherwise be impossible. We expand our method to enable the coupling of many lineages into niche groups, where differentiated cells are pooled within each niche group. Using this method, we explore the dynamics of the haematopoietic system from a demand control system perspective. We find that coupling together niche lineages allows the organism to regulate blood cell numbers as closely as possible to the homeostatic optimum. Furthermore, coupled lineages respond better than uncoupled ones to random perturbations, here the loss of some myeloid cells. This could imply that it is advantageous for an organism to connect together its niche lineages into groups. Our results suggest that a potential fruitful empirical direction will be to understand how stem cell descendants communicate with the niche and how cancer may arise as a result of a failure of such communication.

  5. The Bone Marrow Microenvironment as Niche Retreats for Hematopoietic and Leukemic Stem Cells

    Directory of Open Access Journals (Sweden)

    Felix Nwajei

    2013-01-01

    Full Text Available Leukemia poses a serious challenge to current therapeutic strategies. This has been attributed to leukemia stem cells (LSCs, which occupy endosteal and sinusoidal niches in the bone marrow similar to those of hematopoietic stem cells (HSCs. The signals from these niches provide a viable setting for the maintenance, survival, and fate specifications of these stem cells. Advancements in genetic engineering and microscopy have enabled us to critically deconstruct and analyze the anatomic and functional characteristics of these niches to reveal a wealth of new knowledge in HSC biology, which is quite ahead of LSC biology. In this paper, we examine the present understanding of the regulatory mechanisms governing HSC niches, with the goals of providing a framework for understanding the mechanisms of LSC regulation and suggesting future strategies for their elimination.

  6. Finding missing interactions of the Arabidopsis thaliana root stem cell niche gene regulatory network

    Directory of Open Access Journals (Sweden)

    Eugenio eAzpeitia

    2013-04-01

    Full Text Available AbstractOver the last few decades, the Arabidopsis thaliana root stem cell niche has become a model system for the study of plant development and the stem cell niche. Currently, many of the molecular mechanisms involved in root stem cell niche maintenance and development have been described. A few years ago, we published a gene regulatory network model integrating this information. This model suggested that there were missing components or interactions. Upon updating the model, the observed stable gene configurations of the root stem cell niche could not be recovered, indicating that there are additional missing components or interactions in the model. In fact, due to the lack of experimental data, gene regulatory networks inferred from published data are usually incomplete. However, predicting the location and nature of the missing data is a not trivial task. Here, we propose a set of procedures for detecting and predicting missing interactions in Boolean networks. We used these procedures to predict putative missing interactions in the A. thaliana root stem cell niche network model. Using our approach, we identified three necessary interactions to recover the reported gene activation configurations that have been experimentally uncovered for the different cell types within the root stem cell niche: 1 a regulation of PHABULOSA to restrict its expression domain to the vascular cells, 2 a self-regulation of WOX5, possibly by an indirect mechanism through the auxin signalling pathway and 3 a positive regulation of JACKDAW by MAGPIE. The procedures proposed here greatly reduce the number of possible Boolean functions that are biologically meaningful and experimentally testable and that do not contradict previous data. We believe that these procedures can be used on any Boolean network. However, because the procedures were designed for the specific case of the root stem cell niche, formal demonstrations of the procedures should be shown in future

  7. 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.

  8. The stem cell niche finds its true north.

    Science.gov (United States)

    Kirkeby, Agnete; Perlmann, Thomas; Pereira, Carlos-Filipe

    2016-08-15

    The third 'Stem Cell Niche' meeting, supported by The Novo Nordisk Foundation, was held this year on May 22-26 and brought together 185 selected participants from 24 different countries to Hillerød, Denmark. Diverse aspects of embryonic and adult stem cell biology were discussed, including their respective niches in ageing, disease and regeneration. Many presentations focused on emerging technologies, including single-cell analysis, in vitro organogenesis and direct reprogramming. Here, we summarize the data presented at this exciting and highly enjoyable meeting, where speakers as well as kitchen chefs were applauded at every session. PMID:27531947

  9. 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

  10. Engineering stem cell niches in bioreactors

    OpenAIRE

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “ni...

  11. The hematopoietic stem cell and its niche: a comparative view.

    Science.gov (United States)

    Martinez-Agosto, Julian A; Mikkola, Hanna K A; Hartenstein, Volker; Banerjee, Utpal

    2007-12-01

    Stem cells have been identified as a source of virtually all highly differentiated cells that are replenished during the lifetime of an animal. The critical balance between stem and differentiated cell populations is crucial for the long-term maintenance of functional tissue types. Stem cells maintain this balance by choosing one of several alternate fates: self-renewal, commitment to differentiate, and senescence or cell death. These characteristics comprise the core criteria by which these cells are usually defined. The self-renewal property is important, as it allows for extended production of the corresponding differentiated cells throughout the life span of the animal. A microenvironment that is supportive of stem cells is commonly referred to as a stem cell niche. In this review, we first present some general concepts regarding stem cells and their niches, comparing stem cells of many different kinds from diverse organisms, and in the second part, we compare specific aspects of hematopoiesis and the niches that support hematopoiesis in Drosophila, zebrafish and mouse. PMID:18056420

  12. Maintenance of Stem Cell Niche Integrity by a Novel Activator of Integrin Signaling.

    OpenAIRE

    Joo Yeun Lee; Chen, Jessica Y.; Jillian L Shaw; Chang, Karen T.

    2016-01-01

    Stem cells depend critically on the surrounding microenvironment, or niche, for their maintenance and self-renewal. While much is known about how the niche regulates stem cell self-renewal and differentiation, mechanisms for how the niche is maintained over time are not well understood. At the apical tip of the Drosophila testes, germline stem cells (GSCs) and somatic stem cells share a common niche formed by hub cells. Here we demonstrate that a novel protein named Shriveled (Shv) is necessa...

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

    Science.gov (United States)

    Hsu, Ya-Chieh; Fuchs, Elaine

    2012-02-01

    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. PMID:22266760

  14. A new image of the hematopoietic stem cell vascular niche

    OpenAIRE

    Silberstein, Leslie E.; Lin, Charles P.

    2013-01-01

    The microenvironment within the bone marrow that maintains hematopoietic stem cell (HSC) quiescence is the subject of intense study. In a recent Nature paper, Kunisaki et al combine imaging techniques and computational modeling to define a novel arteriolar niche for quiescent HSCs within the bone marrow.

  15. Simulation of proliferation and differentiation of cells in a stem-cell niche

    Science.gov (United States)

    Zhdanov, Vladimir P.

    2008-10-01

    Stem-cell niches represent microscopic compartments formed of environmental cells that nurture stem cells and enable them to maintain tissue homeostasis. The spatio-temporal kinetics of proliferation and differentiation of cells in such niches depend on the specifics of the niche structure and on adhesion and communication between cells and may also be influenced by spatial constraints on cell division. We propose a generic lattice model, taking all these factors into account, and systematically illustrate their role. The model is motivated by the experimental data available for the niches located in the subventricular zone of adult mammalian brain. The general conclusions drawn from our Monte Carlo simulations are applicable to other niches as well. One of our main findings is that the kinetics under consideration are highly stochastic due to a relatively small number of cells proliferating and differentiating in a niche and the autocatalytic character of the symmetric cell division. In particular, the kinetics exhibit huge stochastic bursts especially if the adhesion between cells is taken into account. In addition, the results obtained show that despite the small number of cells present in stem-cell niches, their arrangement can be predetermined to appreciable extent provided that the adhesion of different cells is different so that they tend to segregate.

  16. 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.

  17. The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in (Review)

    OpenAIRE

    Ehninger, A; Trumpp, A

    2011-01-01

    Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as well as the engagement of specific programs in response to stress. In mammals, the best understood niche is that harboring bone marrow hematopoietic stem cells (HSCs). Recent studies have expanded the number of cell types contributing to the HSC...

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

    Science.gov (United States)

    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.

  19. A stromal cell niche for human and mouse type 3 innate lymphoid cells

    OpenAIRE

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

    2015-01-01

    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 ...

  20. Enabling stem cell therapies through synthetic stem cell–niche engineering

    OpenAIRE

    Peerani, Raheem; Zandstra, Peter W.

    2010-01-01

    Enabling stem cell–targeted therapies requires an understanding of how to create local microenvironments (niches) that stimulate endogenous stem cells or serve as a platform to receive and guide the integration of transplanted stem cells and their derivatives. In vivo, the stem cell niche is a complex and dynamic unit. Although components of the in vivo niche continue to be described for many stem cell systems, how these components interact to modulate stem cell fate is only beginning to be u...

  1. 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.

  2. 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.

  3. 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.

  4. Stem Cell Niches in Glioblastoma: A Neuropathological View

    Directory of Open Access Journals (Sweden)

    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.

  5. Cigarette Smoke Alters the Hematopoietic Stem Cell Niche

    Directory of Open Access Journals (Sweden)

    Robert W. Siggins

    2014-02-01

    Full Text Available Effects of tobacco smoke on hematologic derangements have received little attention. This study employed a mouse model of cigarette smoke exposure to explore the effects on bone marrow niche function. While lung cancer is the most widely studied consequence of tobacco smoke exposure, other malignancies, including leukemia, are associated with tobacco smoke exposure. Animals received cigarette smoke exposure for 6 h/day, 5 days/week for 9 months. Results reveal that the hematopoietic stem and progenitor cell (HSPC pool size is reduced by cigarette smoke exposure. We next examined the effect of cigarette smoke exposure on one supporting cell type of the niche, the mesenchymal stromal cells (MSCs. Smoke exposure decreased the number of MSCs. Transplantation of naïve HSPCs into irradiated mice with cigarette smoke exposure yielded fewer numbers of engrafted HSPCs. This result suggests that smoke-exposed mice possess dysfunctional niches, resulting in abnormal hematopoiesis. Co-culture experiments using MSCs isolated from control or cigarette smoke-exposed mice with naïve HSPCs in vitro showed that MSCs from cigarette smoke-exposed mice generated marked expansion of naïve HSPCs. These data show that cigarette smoke exposure decreases in vivo MSC and HSC number and also increases pro-proliferative gene expression by cigarette smoke-exposed MSCs, which may stimulate HSPC expansion. These results of this investigation are clinically relevant to both bone marrow donors with a history of smoking and bone marrow transplant (BMT recipients with a history of smoking.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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...

  9. Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence

    DEFF Research Database (Denmark)

    Lataillade, J.J.; Pierre-Louis, O.; Uzan, G.;

    2008-01-01

    Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model...... in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches...... are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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. PMID:27633818

  12. Interactions between structural and chemical biomimetism in synthetic stem cell niches

    International Nuclear Information System (INIS)

    Advancements in understanding stem cell functions and differentiation are of key importance for the clinical success of stem-cell-based therapies. 3D structural niches fabricated by two-photon polymerization are a powerful platform for controlling stem cell growth and differentiation. In this paper, we investigate the possibility of further controlling stem cell fate by tuning the mechanical properties of such niches through coating with thin layers of biomimetic hyaluronan-based and gelatin-based hydrogels. We first assess the biocompatibility of chemical coatings and then study the interactions between structural and chemical biomimetism on the response of MSCs in terms of proliferation and differentiation. We observed a clear effect of the hydrogel coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated niches we observed a stronger metabolic activity and commitment toward the osteo-chondral lineage with respect to hyaluronan-coated niches. Conversely, a reduction in the homing effect was observed in all the coated niches, especially in gelatin-coated niches. This study demonstrates the feasibility of controlling independently different mechanical cues, in bioengineered stem cell niches, i.e. the 3D scaffold geometry and the surface stiffness. This will allow, on the one hand, understanding their specific role in stem cell proliferation and differentiation and, on the other hand, finely tuning their synergistic effect. (paper)

  13. 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.

  14. A causal relation between bioluminescence and oxygen to quantify the cell niche

    OpenAIRE

    Lambrechts, Dennis; Roeffaers, Maarten; Goossens, Karel; Hofkens, Johan; Vande Velde, Greetje; Van de Putte, Tom; Schrooten, Jan; Van Oosterwyck, Hans

    2014-01-01

    Bioluminescence imaging assays have become a widely integrated technique to quantify effectiveness of cell-based therapies by monitoring fate and survival of transplanted cells. To date these assays are still largely qualitative and often erroneous due to the complexity and dynamics of local micro-environments (niches) in which the cells reside. Here, we report, using a combined experimental and computational approach, on oxygen that besides being a critical niche component responsible for ce...

  15. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

    OpenAIRE

    Méndez-Ferrer, Simón; Michurina, Tatyana V.; Ferraro, Francesca; Amin R Mazloom; MacArthur, Ben D; Lira, Sergio A.; Scadden, David T.; Ma’ayan, Avi; Enikolopov, Grigori N.; Frenette, Paul S.

    2010-01-01

    The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial tr...

  16. The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Drosophila Ovary

    OpenAIRE

    Sarikaya, Didem P.; Extavour, Cassandra G.

    2015-01-01

    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 c...

  17. 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.

  18. Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

    OpenAIRE

    Tian Li; Yaojiong Wu

    2011-01-01

    Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation.

  19. 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

  20. 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.

  1. 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.

  2. Brain micro-ecologies: neural stem cell niches in the adult mammalian brain

    OpenAIRE

    Riquelme, Patricio A; Drapeau, Elodie; Doetsch, Fiona

    2007-01-01

    Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affect...

  3. 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.

  4. Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells.

    Directory of Open Access Journals (Sweden)

    Wen Lu

    Full Text Available BACKGROUND: Drosophila female germline stem cells (GSCs reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division. METHODS AND FINDINGS: Here we show that GSCs are polarized with respect to the cellular niche. We first use a modified biosensor to demonstrate that the small GTPase Rac is asymmetrically activated within the GSC at the niche-GSC interface. Experiments using loss-of-function and gain-of-function mutations in Rac indicate that asymmetric Rac activity both localizes the microtubule binding protein Apc2 to orient one GSC centrosome at the niche-GSC interface during interphase and activates the Jun N-terminal kinase pathway to increase the ability of the GSC to respond to BMP ligands. Other processes act in concert with each function of Rac. Specifically, we demonstrate that the GSC cell cycle arrests at prometaphase if centrosomes are misoriented. CONCLUSIONS: Thus, the GSCs, an adult stem cell present in a cellular niche, have a niche-associated polarity that couples control of the division plane with increased response to an extracellular maintenance signal. Other processes work in parallel with the Rac-mediated polarity to ensure a robust pattern of asymmetric division. We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis.

  5. In vivo imaging of Tregs providing immune privilege to the hematopoietic stem cell niche

    Science.gov (United States)

    Fujisaki, Joji; Wu, Juwell; Carlson, Alicia L.; Silberstein, Lev; Putheti, Prabhakar; Larocca, Rafael; Gao, Wenda; Saito, Toshiki I.; Celso, Cristina Lo; Tsuyuzaki, Hitoshi; Sato, Tatsuyuki; Côté, Daniel; Sykes, Megan; Strom, Terry B.; Scadden, David T.; Lin, Charles P.

    2013-01-01

    Stem cells reside in a specialized regulatory microenvironment or niche1,2, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity1-3. The niche may also protect stem cells from environmental insults3 including cytotoxic chemotherapy and perhaps pathogenic immunity4. The testis, hair follicle, and placenta are all sites of residence for stem cells and are immune suppressive environments, called immune privileged (IP) sites, where multiple mechanisms conspire to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression (IS)4. We sought to determine if somatic stem cell niches more broadly are IP sites by examining the hematopoietic stem/progenitor cell (HSPC) niche1,2,5-7 in the bone marrow (BM), a site where immune reactivity exists8,9. We observed persistence of allo-HSPCs in non-irradiated recipients for 30 days without IS with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T cells (Tregs). High resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with Tregs that accumulated on the endosteal surface in the calvarial and trabecular BM. Tregs appear to participate in creating a localized zone where HSPCs reside and where Tregs are necessary for allo-HSPC persistence. In addition to processes supporting stem cell function, the niche will provide a relative sanctuary from immune attack. PMID:21654805

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

    2013-03-01

    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 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

  8. 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

    2013-03-01

    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 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

  9. 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.

  10. Age-related human small intestine methylation: evidence for stem cell niches

    Directory of Open Access Journals (Sweden)

    Tavaré Simon

    2005-06-01

    Full Text Available Abstract Background The small intestine is constructed of many crypts and villi, and mouse studies suggest that each crypt contains multiple stem cells. Very little is known about human small intestines because mouse fate mapping strategies are impractical in humans. However, it is theoretically possible that stem cell histories are inherently written within their genomes. Genomes appear to record histories (as exemplified by use of molecular clocks, and therefore it may be possible to reconstruct somatic cell dynamics from somatic cell errors. Recent human colon studies suggest that random somatic epigenetic errors record stem cell histories (ancestry and total numbers of divisions. Potentially age-related methylation also occurs in human small intestines, which would allow characterization of their stem cells and comparisons with the colon. Methods Methylation patterns in individual crypts from 13 small intestines (17 to 78 years old were measured by bisulfite sequencing. The methylation patterns were analyzed by a quantitative model to distinguish between immortal or niche stem cell lineages. Results Age-related methylation was observed in the human small intestines. Crypt methylation patterns were more consistent with stem cell niches than immortal stem cell lineages. Human large and small intestine crypt niches appeared to have similar stem cell dynamics, but relatively less methylation accumulated with age in the small intestines. There were no apparent stem cell differences between the duodenum and ileum, and stem cell survival did not appear to decline with aging. Conclusion Crypt niches containing multiple stem cells appear to maintain human small intestines. Crypt niches appear similar in the colon and small intestine, and the small intestinal stem cell mitotic rate is the same as or perhaps slower than that of the colon. Although further studies are needed, age-related methylation appears to record somatic cell histories, and a

  11. 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.

  12. Redox and Metabolic Regulation of Stem/Progenitor Cells and Their Niche

    OpenAIRE

    Ushio-Fukai, Masuko; Rehman, Jalees

    2014-01-01

    Stem cells are defined as cells that have the capacity to self-renew and exhibit multipotency or pluripotency, whereas progenitor cells are committed to selected lineages but retain their self-renewal capacity. The stem or progenitor cell niche refers to the microenvironment of the regenerative cells in the bone marrow (BM) or other tissues such as the heart. It can regulate self-renewal, differentiation, migration, and proliferation of regenerative stem/progenitor cells. The precise regulato...

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

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-01

    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. PMID:25931262

  14. Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

    Science.gov (United States)

    Ogino, Takashi; Sawada, Masato; Takase, Hiroshi; Nakai, Chiemi; Herranz-Pérez, Vicente; Cebrián-Silla, Arantxa; Kaneko, Naoko; García-Verdugo, José Manuel; Sawamoto, Kazunobu

    2016-10-15

    In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991819

  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...

  16. The canine hepatic progenitor cell niche : molecular characterisation in health and disease

    NARCIS (Netherlands)

    Kruitwagen, H S; Spee, B; Viebahn, C S; Venema, H B; Penning, L C; Grinwis, G C M; Favier, R P; van den Ingh, T S G A M; Rothuizen, J; Schotanus, B A

    2014-01-01

    Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver that contributes to liver regeneration when replication of mature hepatocytes is insufficient. In this study, laser microdissection was used to isolate HPC niches from the livers of healthy dogs and dogs with lobular dis

  17. 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.

  18. 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.

  19. Mesenchymal morphogenesis of embryonic stem cells dynamically modulates the biophysical microtissue niche

    OpenAIRE

    Kinney, Melissa A.; Rabbia Saeed; McDevitt, Todd C.

    2014-01-01

    Stem cell fate and function are dynamically modulated by the interdependent relationships between biochemical and biophysical signals constituting the local 3D microenvironment. While approaches to recapitulate the stem cell niche have been explored for directing stem cell differentiation, a quantitative relationship between embryonic stem cell (ESC) morphogenesis and intrinsic biophysical cues within three-dimensional microtissues has not been established. In this study, we demonstrate that ...

  20. 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.

  1. 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.

  2. The role of the bi-compartmental stem cell niche in delaying cancer

    Science.gov (United States)

    Shahriyari, Leili; Komarova, Natalia L.

    2015-10-01

    In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

  3. Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells

    OpenAIRE

    Schaniel, Christoph; Sirabella, Dario; Qiu, Jiajing; Niu, Xiaohong; Lemischka, Ihor R.; Moore, Kateri A.

    2011-01-01

    The role of Wnt signaling in hematopoietic stem cell fate decisions remains controversial. We elected to dysregulate Wnt signaling from the perspective of the stem cell niche by expressing the pan Wnt inhibitor, Wnt inhibitory factor 1 (Wif1), specifically in osteoblasts. Here we report that osteoblastic Wif1 overexpression disrupts stem cell quiescence, leading to a loss of self-renewal potential. Primitive stem and progenitor populations were more proliferative and elevated in bone marrow a...

  4. One size does not fit all: developing a cell-specific niche for in vitro study of cell behavior.

    Science.gov (United States)

    Marinkovic, Milos; Block, Travis J; Rakian, Rubie; Li, Qihong; Wang, Exing; Reilly, Matthew A; Dean, David D; Chen, Xiao-Dong

    2016-01-01

    For more than 100years, cells and tissues have been studied in vitro using glass and plastic surfaces. Over the last 10-20years, a great body of research has shown that cells are acutely sensitive to their local environment (extracellular matrix, ECM) which contains both chemical and physical cues that influence cell behavior. These observations suggest that modern cell culture systems, using tissue culture polystyrene (TCP) surfaces, may fail to reproduce authentic cell behavior in vitro, resulting in "artificial outcomes." In the current study, we use bone marrow (BM)- and adipose (AD)-derived stromal cells to prepare BM-ECM and AD-ECM, which are decellularized after synthesis by the cells, to mimic the cellular niche for each of these tissues. Each ECM was characterized for its ability to affect BM- and AD-mesenchymal stem cell (MSC) proliferation, as well as proliferation of three cancer cell lines (HeLa, MCF-7, and MDA-MB-231), modulate cell spreading, and direct differentiation relative to standard TCP surfaces. We found that both ECMs promoted the proliferation of MSCs, but that this effect was enhanced when the tissue-origin of the cells matched that of the ECM (i.e. BM-ECM promoted the proliferation of BM-MSCs over AD-MSCs, and vice versa). Moreover, BM- and AD-ECM were shown to preferentially direct MSC differentiation towards either osteogenic or adipogenic lineage, respectively, suggesting that the effects of the ECM were tissue-specific. Further, each ECM influenced cell morphology (i.e. circularity), irrespective of the origin of the MSCs, lending more support to the idea that effects were tissue specific. Interestingly, unlike MSCs, these ECMs did not promote the proliferation of the cancer cells. In an effort to further understand how these three culture substrates influence cell behavior, we evaluated the chemical (protein composition) and physical properties (architecture and mechanical) of the two ECMs. While many structural proteins (e

  5. The canine hepatic progenitor cell niche: molecular characterisation in health and disease.

    Science.gov (United States)

    Kruitwagen, H S; Spee, B; Viebahn, C S; Venema, H B; Penning, L C; Grinwis, G C M; Favier, R P; van den Ingh, T S G A M; Rothuizen, J; Schotanus, B A

    2014-09-01

    Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver that contributes to liver regeneration when replication of mature hepatocytes is insufficient. In this study, laser microdissection was used to isolate HPC niches from the livers of healthy dogs and dogs with lobular dissecting hepatitis (LDH), in which HPCs are massively activated. Gene expression of HPC, hepatocyte and biliary markers was determined by quantitative reverse transcriptase PCR. Expression and localisation of selected markers were further studied at the protein level by immunohistochemistry and immunofluorescent double staining in samples of normal liver and liver from dogs with LDH, acute and chronic hepatitis, and extrahepatic cholestasis. Activated HPC niches had higher gene expression of the hepatic progenitor markers OPN, FN14, CD29, CD44, CD133, LIF, LIFR and BMI1 compared to HPCs from normal liver. There was lower expression of albumin, but activated HPC niches were positive for the biliary markers SOX9, HNF1β and keratin 19 by immunohistochemistry and immunofluorescence. Laminin, activated stellate cells and macrophages are abundant extracellular matrix and cellular components of the canine HPC niche. This study demonstrates that the molecular and cellular characteristics of canine HPCs are similar to rodent and human HPCs, and that canine HPCs are distinctively activated in different types of liver disease. PMID:24923752

  6. Keeping stem cells under control: New insights into the mechanisms that limit niche-stem cell signaling within the reproductive system.

    Science.gov (United States)

    Inaba, Mayu; Yamashita, Yukiko M; Buszczak, Michael

    2016-08-01

    Adult stem cells reside in specialized microenvironments, called niches, that maintain stem cells in an undifferentiated and self-renewing state. Defining and understanding the mechanisms that restrict niche signaling exclusively to stem cells is crucial to determine how stem cells undergo self-renewal while their progeny, often located just one cell diameter away from the niche, differentiate. Despite extensive studies on the signaling pathways that operate within stem cells and their niches, how this segregation occurs remains elusive. Here we review recent progress on the characterization of niche-stem cell interactions, with a focus on emerging mechanisms that spatially restrict niche signaling. Mol. Reprod. Dev. 83: 675-683, 2016 © 2016 Wiley Periodicals, Inc. PMID:27434704

  7. Perlecan is required for FGF-2 signaling in the neural stem cell niche

    Directory of Open Access Journals (Sweden)

    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  8. 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.

  9. Engineering of the Embryonic and Adult Stem Cell Niches

    OpenAIRE

    Hosseinkhani, Mohsen; Shirazi, Reza; Rajaei, Farzad; Mahmoudi, Masoud; Mohammadi, Navid; Abbasi, Mahnaz

    2013-01-01

    Context Stem cells have the potential to generate a renewable source of cells for regenerative medicine due to their ability to self-renew and differentiate to various functional cell types of the adult organism. The extracellular microenvironment plays a pivotal role in controlling stem cell fate responses. Therefore, identification of appropriate environmental stimuli that supports cellular proliferation and lineage-specific differentiation is critical for the clinical application of the st...

  10. 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.

  11. The Glandular Stem/Progenitor Cell Niche in Airway Development and Repair

    OpenAIRE

    Liu, Xiaoming; Engelhardt, John F.

    2008-01-01

    Airway submucosal glands (SMGs) are major secretory structures that lie beneath the epithelium of the cartilaginous airway. These glands are believed to play important roles in normal lung function and airway innate immunity by secreting antibacterial factors, mucus, and fluid into the airway lumen. Recent studies have suggested that SMGs may additionally serve as a protective niche for adult epithelial stem/progenitor cells of the proximal airways. As in the case of other adult stem cell nic...

  12. 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.

  13. 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.

  14. Neovascular niche for human myeloma cells in immunodeficient mouse bone.

    Directory of Open Access Journals (Sweden)

    Hirono Iriuchishima

    Full Text Available The interaction with bone marrow (BM plays a crucial role in pathophysiological features of multiple myeloma (MM, including cell proliferation, chemoresistance, and bone lesion progression. To characterize the MM-BM interactions, we utilized an in vivo experimental model for human MM in which a GFP-expressing human MM cell line is transplanted into NOG mice (the NOG-hMM model. Transplanted MM cells preferentially engrafted at the metaphyseal region of the BM endosteum and formed a complex with osteoblasts and osteoclasts. A subpopulation of MM cells expressed VE-cadherin after transplantation and formed endothelial-like structures in the BM. CD138(+ myeloma cells in the BM were reduced by p53-dependent apoptosis following administration of the nitrogen mustard derivative bendamustine to mice in the NOG-hMM model. Bendamustine maintained the osteoblast lining on the bone surface and protected extracellular matrix structures. Furthermore, bendamustine suppressed the growth of osteoclasts and mesenchymal cells in the NOG-hMM model. Since VE-cadherin(+ MM cells were chemoresistant, hypoxic, and HIF-2α-positive compared to the VE-cadherin(- population, VE-cadherin induction might depend on the oxygenation status. The NOG-hMM model described here is a useful system to analyze the dynamics of MM pathophysiology, interactions of MM cells with other cellular compartments, and the utility of novel anti-MM therapies.

  15. TRAPping telomerase within the intestinal stem cell niche

    OpenAIRE

    Pech, Matthew F.; Artandi, Steven E.

    2011-01-01

    Recent work from Hans Clevers' lab reveals high telomerase activity and telomere length in dividing LGR5-positive intestinal stem cells. They further report random chromosome segregation and thus challenge the ‘immortal strand' hypothesis at least for this stem cell population.

  16. 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.

  17. An artificial niche preserves the quiescence of muscle stem cells and enhances their therapeutic efficacy.

    Science.gov (United States)

    Quarta, Marco; Brett, Jamie O; DiMarco, Rebecca; De Morree, Antoine; Boutet, Stephane C; Chacon, Robert; Gibbons, Michael C; Garcia, Victor A; Su, James; Shrager, Joseph B; Heilshorn, Sarah; Rando, Thomas A

    2016-07-01

    A promising therapeutic strategy for diverse genetic disorders involves transplantation of autologous stem cells that have been genetically corrected ex vivo. A major challenge in such approaches is a loss of stem cell potency during culture. Here we describe an artificial niche for maintaining muscle stem cells (MuSCs) in vitro in a potent, quiescent state. Using a machine learning method, we identified a molecular signature of quiescence and used it to screen for factors that could maintain mouse MuSC quiescence, thus defining a quiescence medium (QM). We also engineered muscle fibers that mimic the native myofiber of the MuSC niche. Mouse MuSCs maintained in QM on engineered fibers showed enhanced potential for engraftment, tissue regeneration and self-renewal after transplantation in mice. An artificial niche adapted to human cells similarly extended the quiescence of human MuSCs in vitro and enhanced their potency in vivo. Our approach for maintaining quiescence may be applicable to stem cells isolated from other tissues. PMID:27240197

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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. PMID:24613913

  2. Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.

    Directory of Open Access Journals (Sweden)

    Rui Lan Zhang

    Full Text Available The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP positive neural stem cells that are in contact with the cerebrospinal fluid (CSF via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction.

  3. Lung epithelial stem cells and their niches: Fgf10 takes center stage.

    Science.gov (United States)

    Volckaert, Thomas; De Langhe, Stijn

    2014-01-01

    Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF). PMID:24891877

  4. Rampant infections of bone marrow stem cell niches as triggers for spondyloarthropathies and rheumatoid arthritis.

    Science.gov (United States)

    Berthelot, Jean-Marie; Sibilia, Jean

    2016-01-01

    Tropheryma Whipplei can induce rheumatism mimicking SpA or RA, but even more rampant bacterial/viral infections in epiphyseal bones could also contribute to the onset of RA and SpA. Indeed, as bone marrow stem cell niches are enriched in Tregs and myeloid derived suppressor cells, these areas are favourable for the persistence of quiescent viruses and/or dormant bacteria. This review focuses on the possibility that such silent infections of bone marrow stem cell niches might contribute to the pathogenesis of SpA and RA, at least during their onset. Some infections can affect the bone marrow mesenchymal stem cells, which can transmit these pathogens to their progeny. Transient but repeated revivals of viruses or dormant bacteria could promote the conversion of marrow regulatory T cells into effector phenotypes, leading to autoimmunity in the epiphyseal bone marrow, entheses and adjacent synovium. This scenario would also fit the flares of rheumatic disorders and explain why some joints or enthuses can be severely involved whereas their neighbours remain intact. The efficiency of anti-TNF drugs does not rule out a role of persistent infections in SpA and RA. These drugs do not affect chlamydial clearance, or the reactivation of latent Salmonella enterica serovar Typhimurium in mice or Epstein-Barr virus in humans. Anti-TNF might even prevent, rather than foster, the revival of dormant bacteria and viruses in marrow stem cell niches. Indeed, anti-TNF enhance the maturation of the immunosuppressive immature myeloid cells around stem cells into dendritic cells and macrophages, thus restoring immune responses in these areas. PMID:26886813

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

    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.

    2012-01-01

    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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    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 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. PMID:26473842

  11. 肿瘤干细胞niche与肿瘤%Cancer stem cell niche and cancer

    Institute of Scientific and Technical Information of China (English)

    张海谱

    2010-01-01

    Cancer stem cell (CSC) is the source of tumor development and metastasis, and may become the target of cancer therapy in the future. Niche refers to a micro-environment that makes up the basis of stem cell existence. Niche is involved in tumor development by regulating the growth and changes of CSC. It is also closely related to tumor migration and metastasis. Eradicating CSC through modifying niche may be a new therapeutic strategy for curing cancer.%肿瘤干细胞(CSC)是肿瘤发生、发展、转移的根源,是未来肿瘤治疗的靶标.niche指一种微环境,是干细胞存在的基础.niche通过调控CSC的生长变化而参与肿瘤的发生发展,与肿瘤转移迁徙也密切相关,通过影响niche而根除CSC治愈肿瘤是一种新的治疗肿瘤的策略.

  12. Osteoblastic and Vascular Endothelial Niches, Their Control on Normal Hematopoietic Stem Cells, and Their Consequences on the Development of Leukemia

    Directory of Open Access Journals (Sweden)

    Bella S. Guerrouahen

    2011-01-01

    Full Text Available Stem cell self-renewal is regulated by intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments called “niches.” The best-characterized stem cell is the hematopoietic stem cell (HSC. Self-renewal and differentiation ability of HSC are regulated by two major elements: endosteal and vascular regulatory elements. The osteoblastic niche localized at the inner surface of the bone cavity might serve as a reservoir for long-term HSC storage in a quiescent state. Whereas the vascular niche, which consists of sinusoidal endothelial cell lining blood vessel, provides an environment for short-term HSC proliferation and differentiation. Both niches act together to maintain hematopoietic homeostasis. In this paper, we provide some principles applying to the hematopoietic niches, which will be useful in the study and understanding of other stem cell niches. We will discuss altered microenvironment signaling leading to myeloid lineage disease. And finally, we will review some data on the development of acute myeloid leukemia from a subpopulation called leukemia-initiating cells (LIC, and we will discuss on the emerging evidences supporting the influence of the microenvironment on chemotherapy resistance.

  13. 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.

  14. Stem Cell Interaction with Somatic Niche May Hold the Key to Fertility Restoration in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Deepa Bhartiya

    2012-01-01

    Full Text Available The spontaneous return of fertility after bone marrow transplantation or heterotopic grafting of cryopreserved ovarian cortical tissue has surprised many, and a possible link with stem cells has been proposed. We have reviewed the available literature on ovarian stem cells in adult mammalian ovaries and presented a model that proposes that the ovary harbors two distinct populations of stem cells, namely, pluripotent, quiescent, very small embryonic-like stem cells (VSELs, and slightly larger “progenitor” ovarian germ stem cells (OGSCs. Besides compromising the somatic niche, oncotherapy destroys OGSCs since, like tumor cells, they are actively dividing; however VSELs persist since they are relatively quiescent. BMT or transplanted ovarian cortical tissue may help rejuvenate the ovarian niche, which possibly supports differentiation of persisting VSELs resulting in neo-oogenesis and follicular development responsible for successful pregnancies. Postnatal oogenesis in mammalian ovary from VSELs may be exploited for fertility restoration in cancer survivors including those who were earlier deprived of gametes and/or gonadal tissue cryopreservation options.

  15. Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury.

    Science.gov (United States)

    Volckaert, Thomas; Dill, Erik; Campbell, Alice; Tiozzo, Caterina; Majka, Susan; Bellusci, Saverio; De Langhe, Stijn P

    2011-11-01

    During lung development, parabronchial SMC (PSMC) progenitors in the distal mesenchyme secrete fibroblast growth factor 10 (Fgf10), which acts on distal epithelial progenitors to promote their proliferation. β-catenin signaling within PSMC progenitors is essential for their maintenance, proliferation, and expression of Fgf10. Here, we report that this Wnt/Fgf10 embryonic signaling cascade is reactivated in mature PSMCs after naphthalene-induced injury to airway epithelium. Furthermore, we found that this paracrine Fgf10 action was essential for activating surviving variant Clara cells (the cells in the airway epithelium from which replacement epithelial cells originate) located at the bronchoalveolar duct junctions and adjacent to neuroendocrine bodies. After naphthalene injury, PSMCs secreted Fgf10 to activate Notch signaling and induce Snai1 expression in surviving variant Clara cells, which subsequently underwent a transient epithelial to mesenchymal transition to initiate the repair process. Epithelial Snai1 expression was important for regeneration after injury. We have therefore identified PSMCs as a stem cell niche for the variant Clara cells in the lung and established that paracrine Fgf10 signaling from the niche is critical for epithelial repair after naphthalene injury. These findings also have implications for understanding the misregulation of lung repair in asthma and cancer. PMID:21985786

  16. Mesenchymal morphogenesis of embryonic stem cells dynamically modulates the biophysical microtissue niche

    Science.gov (United States)

    Kinney, Melissa A.; Saeed, Rabbia; McDevitt, Todd C.

    2014-01-01

    Stem cell fate and function are dynamically modulated by the interdependent relationships between biochemical and biophysical signals constituting the local 3D microenvironment. While approaches to recapitulate the stem cell niche have been explored for directing stem cell differentiation, a quantitative relationship between embryonic stem cell (ESC) morphogenesis and intrinsic biophysical cues within three-dimensional microtissues has not been established. In this study, we demonstrate that mesenchymal embryonic microtissues induced by BMP4 exhibited increased stiffness and viscosity accompanying differentiation, with cytoskeletal tension significantly contributing to multicellular stiffness. Perturbation of the cytoskeleton during ESC differentiation led to modulation of the biomechanical and gene expression profiles, with the resulting cell phenotype and biophysical properties being highly correlated by multivariate analyses. Together, this study elucidates the dynamics of biophysical and biochemical signatures within embryonic microenvironments, with broad implications for monitoring tissue dynamics, modeling pathophysiological and embryonic morphogenesis and directing stem cell patterning and differentiation. PMID:24598818

  17. Vascular-derived TGF-β increases in the stem cell niche and perturbs neuro-genesis during aging and following irradiation in the adult mouse brain

    International Nuclear Information System (INIS)

    Neuro-genesis decreases during aging and following cranial radiotherapy, causing a progressive cognitive decline that is currently untreatable. However, functional neural stem cells remained present in the sub-ventricular zone of high dose irradiated and aged mouse brains. We therefore investigated whether alterations in the neurogenic niches are perhaps responsible for the neuro-genesis decline. This hypothesis was supported by the absence of proliferation of neural stem cells that were engrafted into the vascular niches of irradiated host brains. Moreover, we observed a marked increase in TGF-β1 production by endothelial cells in the stem cell niche in both middle-aged and irradiated mice. In co-cultures, irradiated brain endothelial cells induced the apoptosis of neural stem/progenitor cells via TGF-β/Smad3 signalling. Strikingly, the blockade of TGF-β signalling in vivo using a neutralizing antibody or the selective inhibitor SB-505124 significantly improved neuro-genesis in aged and irradiated mice, prevented apoptosis and increased the proliferation of neural stem/progenitor cells. These findings suggest that anti-TGF-β-based therapy may be used for future interventions to prevent neurogenic collapse following radiotherapy or during aging. (authors)

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

    Directory of Open Access Journals (Sweden)

    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.

    Directory of Open Access Journals (Sweden)

    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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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. PMID:24532713

  4. 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.

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

    Science.gov (United States)

    Zhou, Hong-Sheng; Carter, Bing Z; Andreeff, Michael

    2016-06-01

    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. PMID:27458532

  6. 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.

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

    Science.gov (United States)

    Zhou, Hong-Sheng; Carter, Bing Z.; Andreeff, Michael

    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.

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

    Directory of Open Access Journals (Sweden)

    Amy S I Wade

    Full Text Available 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.

  9. 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.

  10. Three-dimensional structure of the mammalian limbal stem cell niche.

    Science.gov (United States)

    Grieve, K; Ghoubay, D; Georgeon, C; Thouvenin, O; Bouheraoua, N; Paques, M; Borderie, V M

    2015-11-01

    Although the existence of the limbal stem cell (LSC) niche is accepted, precise knowledge of its three-dimensional (3D) architecture remains incomplete. The LSC niche was explored on freshly excised and organ-cultured corneoscleral rims from human donors (n = 47), pigs (n = 15) and mice (n = 27) with full-field optical coherence microscopy (FFOCM). Limbal crypt features were detected in 90% of organ-cultured human corneoscleral rims, extending between the palisades of Vogt as radially oriented rectangular (74% of eyes) and/or rounded (23% of eyes) forms, often branching off to, or becoming interconnected by, sub-scleral radially or circumferentially oriented crypts (in 56% of eyes). Mean crypt volume represented 16% of sampled limbal volume on the vertical axis and 8% on the horizontal axis. In pigs, palisades were finer and crypts wider with relatively uniform distribution around the eye, and radial orientation, connecting to numerous narrow criss-crossing invaginations beneath the scleral surface. In mice, only a circumferential limbal trough was detected. Mean crypt volume represented 13% of sampled limbal volume in humans and 9% in pigs. FFOCM combined with fluorescence, and confocal fluorescence microscopy, showed presence of p63-α+ cells and cytokeratin-3+ cells in the limbal crypts. To assess colony forming efficiency (CFE), limbal epithelial cells were cultured at low density with mitomycin-arrested 3T3 feeders. CFE increased with limbal crypt volume and was not significantly decreased in organ-cultured cornea, despite degradation of the epithelial roof, suggesting that stem cells remain protected at the base of crypts during organ culture. CFE in human samples was significantly greater than in pig, and CFE in mouse was zero. Crypt architecture in the three species appears associated with eye exposure to light. LSC density increased with percentage limbal volume occupied by crypts. PMID:26297801

  11. Drosophila Follicle Stem Cells are regulated by proliferation and niche adhesion as well as mitochondria and ROS

    OpenAIRE

    Wang, Zhu A.; Huang, Jianhua; Kalderon, Daniel

    2012-01-01

    The mechanisms underlying adult stem cell behavior are likely to be diverse and have not yet been investigated systematically. Here we conducted an unbiased genetic screen using Drosophila ovarian follicle stem cells (FSCs) to probe essential functions regulating self-renewal of epithelial stem cells. Surprisingly, we find that niche adhesion emerge as the most commonly affected essential stem cell property, and that proliferation is critical for stem cell maintenance. We also find that PI3K ...

  12. Immobilized WNT Proteins Act as a Stem Cell Niche for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Molly Lowndes

    2016-07-01

    Full Text Available The timing, location, and level of WNT signaling are highly regulated during embryonic development and for the maintenance of adult tissues. Consequently the ability to provide a defined and directed source of WNT proteins is crucial to fully understand its role in tissue development and to mimic its activity in vitro. Here we describe a one-step immobilization technique to covalently bind WNT3A proteins as a basal surface with easy storage and long-lasting activity. We show that this platform is able to maintain adult and embryonic stem cells while also being adaptable for 3D systems. Therefore, this platform could be used for recapitulating specific stem cell niches with the goal of improving tissue engineering.

  13. 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.

  14. 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

  15. NOTCH1 signaling promotes human T-cell acute lymphoblastic leukemia initiating cell regeneration in supportive niches.

    Directory of Open Access Journals (Sweden)

    Wenxue Ma

    Full Text Available BACKGROUND: Leukemia initiating cells (LIC contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: We established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34(+ cells from NOTCH1(Mutated T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1(Wild-type CD34(+ cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1(Mutated CD34(+ fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1(Mutated T-ALL LIC-engrafted mice and resulted in depletion of CD34(+CD2(+CD7(+ cells that harbor serial transplantation capacity. CONCLUSIONS: These results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Identification of a novel agrin-dependent pathway in cell signaling and adhesion within the erythroid niche.

    Science.gov (United States)

    Anselmo, A; Lauranzano, E; Soldani, C; Ploia, C; Angioni, R; D'amico, G; Sarukhan, A; Mazzon, C; Viola, A

    2016-08-01

    Establishment of cell-cell adhesion is crucial in embryonic development as well as within the stem cell niches of an adult. Adhesion between macrophages and erythroblasts is required for the formation of erythroblastic islands, specialized niches where erythroblasts proliferate and differentiate to produce red blood cells throughout life. The Eph family is the largest known family of receptor tyrosine kinases (RTKs) and controls cell adhesion, migration, invasion and morphology by modulating integrin and adhesion molecule activity and by modifying the actin cytoskeleton. Here, we identify the proteoglycan agrin as a novel regulator of Eph receptor signaling and characterize a novel mechanism controlling cell-cell adhesion and red cell development within the erythroid niche. We demonstrate that agrin induces clustering and activation of EphB1 receptors on developing erythroblasts, leading to the activation of α5β1 integrins. In agreement, agrin knockout mice display severe anemia owing to defective adhesion to macrophages and impaired maturation of erythroid cells. These results position agrin-EphB1 as a novel key signaling couple regulating cell adhesion and erythropoiesis. PMID:26990660

  2. Thymic regulatory T cell niche size is dictated by limiting interleukin 2 from antigen-bearing dendritic cells and feedback competition

    OpenAIRE

    Weist, Brian M.; Kurd, Nadia; Boussier, Jeremy; Chan, Shiao Wei; Robey, Ellen A.

    2015-01-01

    Thymic regulatory T (Treg) cell production requires interleukin 2 (IL-2) and agonist TCR ligands, and is controlled by competition for a limited developmental niche, but the thymic sources of IL-2 and the factors that limit access to the niche are poorly understood. Here we show that IL-2 produced by antigen-bearing dendritic cells plays a key role in Treg cell development, and that existing Treg cells limit new Treg cell development by competing for IL-2. . Our data suggest that antigen-pres...

  3. 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

  4. Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche.

    Science.gov (United States)

    Ye, Haobin; Adane, Biniam; Khan, Nabilah; Sullivan, Timothy; Minhajuddin, Mohammad; Gasparetto, Maura; Stevens, Brett; Pei, Shanshan; Balys, Marlene; Ashton, John M; Klemm, Dwight J; Woolthuis, Carolien M; Stranahan, Alec W; Park, Christopher Y; Jordan, Craig T

    2016-07-01

    Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter CD36. CD36(+) LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment. CD36 also marks a fraction of human blast crisis CML and acute myeloid leukemia (AML) cells with similar biological properties. These findings suggest striking interplay between leukemic cells and AT to create a unique microenvironment that supports the metabolic demands and survival of a distinct LSC subpopulation. PMID:27374788

  5. Eosinophils and megakaryocytes support the early growth of murine MOPC315 myeloma cells in their bone marrow niches.

    Directory of Open Access Journals (Sweden)

    David Wong

    Full Text Available Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315.BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315.BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient ΔdblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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

    Directory of Open Access Journals (Sweden)

    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.

  8. Identification of the Niche and Phenotype of the First Human Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Andrejs Ivanovs

    2014-04-01

    Full Text Available In various vertebrate species, the dorsal aorta (Ao is the site of specification of adult hematopoietic stem cells (HSCs. It has been observed that the upregulation of essential hematopoietic transcription factors and the formation of specific intra-aortic hematopoietic cell clusters occur predominantly in the ventral domain of the Ao (AoV. In the mouse, the first HSCs emerge in the AoV. Here, we demonstrate that in the human embryo the first definitive HSCs also emerge asymmetrically and are localized to the AoV, which thus identifies a functional niche for developing human HSCs. Using magnetic cell separation and xenotransplantations, we show that the first human HSCs are CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA−. This population harbors practically all committed hematopoietic progenitors and is underrepresented in the dorsal domain of the Ao (AoD and urogenital ridges (UGRs. The present study provides a foundation for analysis of molecular mechanisms underpinning embryonic specification of human HSCs.

  9. 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.

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

    International Nuclear Information System (INIS)

    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+/+ 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−/− 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+/+ and Med1−/− MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells

  11. Hematopoietic Stem Cell Activity Is Regulated by Pten Phosphorylation Through a Niche-Dependent Mechanism.

    Science.gov (United States)

    Li, Jing; Zhang, Jun; Tang, Minghui; Xin, Junping; Xu, Yan; Volk, Andrew; Hao, Caiqin; Hu, Chenglong; Sun, Jiewen; Wei, Wei; Cao, Quichan; Breslin, Peter; Zhang, Jiwang

    2016-08-01

    The phosphorylated form of Pten (p-Pten) is highly expressed in >70% of acute myeloid leukemia samples. However, the role of p-Pten in normal and abnormal hematopoiesis has not been studied. We found that Pten protein levels are comparable among long-term (LT) hematopoietic stem cells (HSCs), short-term (ST) HSCs, and multipotent progenitors (MPPs); however, the levels of p-Pten are elevated during the HSC-to-MPP transition. To study whether p-Pten is involved in regulating self-renewal and differentiation in HSCs, we compared the effects of overexpression of p-Pten and nonphosphorylated Pten (non-p-Pten) on the hematopoietic reconstitutive capacity (HRC) of HSCs. We found that overexpression of non-p-Pten enhances the LT-HRC of HSCs, whereas overexpression of p-Pten promotes myeloid differentiation and compromises the LT-HRC of HSCs. Such phosphorylation-regulated Pten functioning is mediated by repressing the cell:cell contact-induced activation of Fak/p38 signaling independent of Pten's lipid phosphatase activity because both p-Pten and non-p-Pten have comparable activity in repressing PI3K/Akt signaling. Our studies suggest that, in addition to repressing PI3K/Akt/mTor signaling, non-p-Pten maintains HSCs in bone marrow niches via a cell-contact inhibitory mechanism by inhibiting Fak/p38 signaling-mediated proliferation and differentiation. In contrast, p-Pten promotes the proliferation and differentiation of HSCs by enhancing the cell contact-dependent activation of Src/Fak/p38 signaling. Stem Cells 2016;34:2130-2144. PMID:27096933

  12. Transcriptome comparison of distinct osteolineage subsets in the hematopoietic stem cell niche using a triple fluorescent transgenic mouse model.

    Science.gov (United States)

    Yu, Vionnie W C; Lymperi, Stefania; Ferraro, Francesca; Scadden, David T

    2015-09-01

    The bone marrow niche is recognized as a central player in maintaining and regulating the behavior of hematopoietic stem and progenitor cells. Specific gain-of and loss-of function experiments perturbing a range of osteolineage cells or their secreted proteins had been shown to affect stem cell maintenance (Calvi et al, 2003 [1]; Stier et al., 2005 [2]; Zhang et al., 2003 [3]; Nilsson et al., 2005 [4]; Greenbaum et al., 2013 [5]) and engraftment (Adam et al., 2006, 2009 [6,7]). We used specific in vivo cell deletion approaches to dissect the niche cell-parenchymal cell dependency in a complex bone marrow microenvironment. Endogenous deletion of osteocalcin-expressing (Ocn(+)) cells led to a loss of T immune cells (Yu et al., 2015 [8]. Ocn(+) cells express the Notch ligand DLL4 to communicate with T-competent progenitors, and thereby ensuring T precursor production and expression of chemotactic molecules on their cell surface for subsequent thymic seeding. In contrast, depletion of osterix-expressing (Osx(+)) osteoprogenitors led to reduced B immune cells. These distinct hematopoietic phenotypes suggest specific pairing of mesenchymal niche cells and parenchymal hematopoietic cells in the bone marrow to create unique functional units to support hematopoiesis. Here, we present the global gene expression profiles of these osteolineage subtypes utilizing a triple fluorescent transgenic mouse model (OsxCre(+);Rosa-mCh(+);Ocn:Topaz(+)) that labels Osx(+) cells red, Ocn(+) cells green, and Osx(+) Ocn(+) cells yellow. This system allows isolation of distinct osteolineage subsets within the same animal by flow cytometry. Array data that have been described in our study [8] are also publically available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE66042. Differences in gene expression may correlate with functional difference in supporting hematopoiesis. PMID:26484277

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

    Directory of Open Access Journals (Sweden)

    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.

  14. c-Kit-mediated functional positioning of stem cells to their niches is essential for maintenance and regeneration of adult hematopoiesis.

    Directory of Open Access Journals (Sweden)

    Yuki Kimura

    Full Text Available The mechanism by which hematopoietic stem and progenitor cells (HSPCs through interaction with their niches maintain and reconstitute adult hematopoietic cells is unknown. To functionally and genetically track localization of HSPCs with their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase technology to conditionally delete c-Kit in adult mice, while simultaneously enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c-Kit resulted in hematopoietic failure and splenic atrophy both at steady state and after marrow ablation leading to the demise of the treated adult mice. Within the marrow, the c-Kit-expressing GFP(+ cells were positioned to Kit ligand (KL-expressing niche cells. This c-Kit-mediated cellular adhesion was essential for long-term maintenance and expansion of HSPCs. These results lay the foundation for delivering KL within specific niches to maintain and restore hematopoiesis.

  15. 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.

  16. Gastrospheres of human gastric mucosa cells: an in vitro model of stromal and epithelial stem cell niche reconstruction.

    Science.gov (United States)

    Santos, Carlos A N; Andrade, Leonardo R; Costa, Márcia H M; Souza, Heitor S P; Granjeiro, José M; Takiya, Christina M; Borojevic, Radovan; Nasciutti, Luiz E

    2016-08-01

    The molecular characterization of mechanisms involved in the gastrointestinal tract disorders needs an in vitro 3D culture model able to mimic the in vivo gastric microenvironment. Herein, we propose a 3D coculture system where gastric epithelial and stromal cells are grown together building spherical and solid structures using the NASA bioreactor - cell culture system (RCCS), a bioreactor. Epithelial and stromal cells from human antral gastric mucosa were isolated from endoscopic gastric biopsies. Thereafter, these cells were mechanically and enzymatically dispersed by treatment with dispase and collagenase, respectively. Using specific culture procedures, these cells formed 3D structures by using a RCCS, named "gastrospheres". Briefly, gastrospheres were obtained by initial seeding of 2.5x10⁴ cells/well in 96 well culture plates. At 24 h after their formation, they were transferred into RCCS, and maintained for 7, 14, 21, and 28 days. The gastrospheres were morphologically characterized by immunocytochemisty to evaluate extracellular matrix (ECM), and by electron microscopy. These analysis of gastrospheres revealed that the epithelial cells were cytokeratin (CK) and lectin reactive and were arranged in the outer layer; stromal cells presented long cytoplasmic processes and were localized inside the gastrosphere. They were vimentin (VIM) and α-smooth muscle actin (α-SMA) positive and expressed ECM components such as laminin (LN), fibronectin (FN), and type IV collagen (CIV). Electron microscopy revealed groups of cohesive gastric cells surrounded by complex stromal structures, with multiple microvilli, and tight cellular junctions interspersed with extracellular matrix fibrils and fibers. The presence of some nestin-positive cells was observed in the inner region of the gastrospheres, suggesting an intermediary localization between epithelial and stromal cells. Altogether, our data suggest that in vitro gastrospheres recapitulate the in vivo gastric niche

  17. The Hemopoietic Stem Cell Niche Versus the Microenvironment of the Multiple Myeloma-Tumor Initiating Cell

    OpenAIRE

    Zipori, Dov

    2010-01-01

    Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from...

  18. Cancer Stem Cells Converted from Pluripotent Stem Cells and the Cancerous Niche

    OpenAIRE

    Kasai, T; Chen, L.; Mizutani, AZ; Kudoh, T.; Murakami, H; Fu, L.; Seno, M

    2014-01-01

    Nowadays, the cancer stem cells are considered to be significantly responsible for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells are typically characterized by continuous proliferation and self-renewal as well as by differentiation potential, while stem cells are considered to differentiate into tissue- specific phenotype of mature cells under the influence of micro-environment. Cancer stem cells should be traced to the stem cells under the influence of a micro-...

  19. 干细胞niche与肿瘤的发生发展%Stem cell niche in genesis and development of cancer

    Institute of Scientific and Technical Information of China (English)

    赵璇; 冉宇靓

    2009-01-01

    干细胞niche是干细胞生存的微环境,在维持干细胞自我更新和分化过程中起着极为关键的作用.肿瘤干细胞在功能异常的niche中生存,控制着肿瘤的发生,适当的niche环境可以促进肿瘤的生长转移.改变特异的niche可以抑制、影响肿瘤的多种恶性表型.%Stem cell niche is the microenvironment in which stem cells reside,and it is essential for stem cells self-renewal and differentiation. Tumor stem cells which live in abnormal niche control tumor genesis,and appropriate niche can promote tumor growth and metastasis. Altering unique niche can suppress and affect malignant phenotypes of tumor.

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

    OpenAIRE

    Hoffman, Robert M.

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis.

    Directory of Open Access Journals (Sweden)

    Qunzhou Zhang

    Full Text Available BACKGROUND: Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their "pathological" niche in the development of the benign tumor. METHODS AND FINDINGS: Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs, which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the "pathological" stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors.

  3. Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin-Producing Cells in Experimental and Human Diabetes.

    Science.gov (United States)

    Carpino, Guido; Puca, Rosa; Cardinale, Vincenzo; Renzi, Anastasia; Scafetta, Gaia; Nevi, Lorenzo; Rossi, Massimo; Berloco, Pasquale B; Ginanni Corradini, Stefano; Reid, Lola M; Maroder, Marella; Gaudio, Eugenio; Alvaro, Domenico

    2016-05-01

    Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, toward pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) toward insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N = 12) or 120 mg/kg (N = 12) of streptozotocin. Liver, pancreas, and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepatopancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with upregulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepatopancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures toward pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the pathophysiology and complications of this disease. Stem Cells 2016;34:1332-1342. PMID:26850087

  4. 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.

  5. The stem cell niche: tissue physiology at a single cell level

    OpenAIRE

    Hoggatt, Jonathan; Scadden, David T.

    2012-01-01

    Stem cells are the critical unit affecting tissue maintenance, regeneration, and repair, with particular relevance to the tissues with high cell turnover. Stem cell regulation accommodates the conflicting needs of prompt responsiveness to injury and long-term preservation through quiescence. They are, in essence, the fundamental unit by which a tissue handles changing physiologic needs throughout the lifetime of the organism. As such, they are the focal point of dynamic tissue function, and t...

  6. Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity.

    Science.gov (United States)

    Kusuma, Gina D; Abumaree, Mohamed H; Pertile, Mark D; Perkins, Anthony V; Brennecke, Shaun P; Kalionis, Bill

    2016-06-01

    The use of mesenchymal stem/stromal cells (MSC) in regenerative medicine often requires MSC to function in environments of high oxidative stress. Human pregnancy is a condition where the mother's tissues, and in particular her circulatory system, are exposed to increased levels of oxidative stress. MSC in the maternal decidua basalis (DMSC) are in a vascular niche, and thus would be exposed to oxidative stress products in the maternal circulation. Aldehyde dehydrogenases (ALDH) are a large family of enzymes which detoxify aldehydes and thereby protect stem cells against oxidative damage. A subpopulation of MSC express high levels of ALDH (ALDH(br)) and these are more potent in repairing and regenerating tissues. DMSC was compared with chorionic villous MSC (CMSC) derived from the human placenta. CMSC reside in vascular niche and are exposed to the fetal circulation, which is in lower oxidative state. We screened an ALDH isozyme cDNA array and determined that relative to CMSC, DMSC expressed high levels of ALDH1 family members, predominantly ALDH1A1. Immunocytochemistry gave qualitative confirmation at the protein level. Immunofluorescence detected ALDH1 immunoreactivity in the DMSC and CMSC vascular niche. The percentage of ALDH(br) cells was calculated by Aldefluor assay and DMSC showed a significantly higher percentage of ALDH(br) cells than CMSC. Finally, flow sorted ALDH(br) cells were functionally potent in colony forming unit assays. DMSC, which are derived from pregnancy tissues that are naturally exposed to high levels of oxidative stress, may be better candidates for regenerative therapies where MSC must function in high oxidative stress environments. PMID:26880140

  7. Regulation of human umbilical cord blood-derived multi-potent stem cells by autogenic osteoclast-based niche-like structure

    International Nuclear Information System (INIS)

    Stem cell niches provide the micro-environment for the development of stem cells. Under our culturing regimen, a kind of osteoclast-centralized structure supports the proliferation of MSCs, derived from human cord blood, once they reside on osteoclasts. MSCs in this structure expressed Oct4 which is a marker of embryonic stem cells. Floating daughter cells of MSCs colony showed abilities to differentiate into osteocyte, adipocyte, and neuronal progenitor cells. Compared with the easy senescence of MSCs without this niche-like structure in vitro, these results suggested that osteoclasts might play an important role the development and maintenance of Umbilical cord blood (UCB)-derived MSCs and might provide a means to expand UCB-MSCs in vitro, more easily, through a stem cell niche-like structure

  8. Tomb niche

    OpenAIRE

    O'Donovan, Danielle

    2004-01-01

    Capital frieze running along jamb of tomb niche. Moulding from the top down comprises: chamfer, frontal fillet, angle-fillet, fillet, angle-fillet, flat surface, angle-fillet, fillet, flat surface. The lower secion can be read as a stepped rebate.

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

  11. From an info-brochure to the Green Power Festival: Eco-current marketing between niche market and mass market. Comparative analysis of marketing strategies and trends in the USA and Switzerland

    International Nuclear Information System (INIS)

    Liberalisation and sustainability pose a dual challenge to the electric power industry. In some countries, public utilities and other suppliers are relying on eco-current as an adequate answer to the challenge. Availabilities and marketing strategies in Switzerland and the USA are compared. It is found that eco-current is still a high-priced niche market commodity in Switzerland. In the USA, on the other hand, professional eco-current suppliers are aiming at mass market introduction in California and Pennsylvania. The author compares marketing concepts and attempts to identify the factors that can make eco-current more than just a niche market commodity also in Switzerland

  12. Illustration of extensive extracellular matrix at the epithelial-mesenchymal interface within the renal stem/progenitor cell niche

    Directory of Open Access Journals (Sweden)

    Minuth Will W

    2012-09-01

    Full Text Available Abstract Background Stem/progenitor cells are promising candidates to treat diseased renal parenchyma. However, implanted stem/progenitor cells are exposed to a harmful atmosphere of degenerating parenchyma. To minimize hampering effects after an implantation investigations are in progress to administer these cells within an artificial polyester interstitum supporting survival. Learning from nature the renal stem/progenitor cell niche appears as a valuable model. At this site epithelial stem/progenitor cells within the collecting duct ampulla face mesenchymal stem/progenitor cells. Both cell types do not have close contact but are separated by a wide interstitium. Methods To analyze extracellular matrix in this particular interstitium, special contrasting for transmission electron microscopy was performed. Kidneys of neonatal rabbits were fixed in solutions containing glutaraldehyde (GA or in combination with cupromeronic blue, ruthenium red and tannic acid. Results GA revealed a basal lamina at the ampulla and a bright but inconspicuously looking interstitial space. In contrast, GA containing cupromeronic blue exhibits numerous proteoglycan braces lining from the ampulla towards the interstitial space. GA containing ruthenium red or tannic acid demonstrates clouds of extracellular matrix protruding from the basal lamina of the ampulla to the surface of mesenchymal stem/progenitor cells. Conclusions The actual data show that the interstitium between epithelial and mesenchymal stem/progenitor cells contains much more and up to date unknown extracellular matrix than earlier observed by classical GA fixation.

  13. Exosomes as novel regulators of adult neurogenic niches

    Directory of Open Access Journals (Sweden)

    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

  14. 干细胞niche与心肌细胞分化的调控机制研究%Regulatory Mechanism of Niche on Stem Cells Differentiation to Cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    余细勇

    2011-01-01

    Stem cells are the special cells of self-renewal and differentiation potential. Recent studies found that the biological behaviors of stem cells are highly dependent on their microenvironment (niche). There are two roles of niche on stem cells: the direct effects between cell contacts, and the indirect effects such as matrix and cytokines which involve in several signal transduction pathways and their cross-talks. Here, we mainly describe the effects of bone marrow niche on mesenchymal stem cells (SMC), and the regulatory mechanisms of MSC differentiation into myocardial cells.%干细胞是一类具有自我更新和多向分化潜能的特殊细胞.研究发现,干细胞的生物学行为高度依赖于其所处的微环境(niche).Niche对干细胞的作用分为细胞与细胞之间的直接作用和基质及众多细胞因子对干细胞的间接作用,涉及多条信号转导通路及其相互作用.本文主要介绍骨髓干细胞的niche对间充质干细胞(MSC)的调控,并探讨MSC向心肌细胞分化的调控机制.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Microcavity arrays as an in vitro model system of the bone marrow niche for hematopoietic stem cells.

    Science.gov (United States)

    Wuchter, Patrick; Saffrich, Rainer; Giselbrecht, Stefan; Nies, Cordula; Lorig, Hanna; Kolb, Stephanie; Ho, Anthony D; Gottwald, Eric

    2016-06-01

    In previous studies human mesenchymal stromal cells (MSCs) maintained the "stemness" of human hematopoietic progenitor cells (HPCs) through direct cell-cell contact in two-dimensional co-culture systems. We establish a three-dimensional (3D) co-culture system based on a custom-made chip, the 3(D)-KITChip, as an in vitro model system of the human hematopoietic stem cell niche. This array of up to 625 microcavities, with 300 μm size in each orientation, was inserted into a microfluidic bioreactor. The microcavities of the 3(D)-KITChip were inoculated with human bone marrow MSCs together with umbilical cord blood HPCs. MSCs used the microcavities as a scaffold to build a complex 3D mesh. HPCs were distributed three-dimensionally inside this MSC network and formed ß-catenin- and N-cadherin-based intercellular junctions to the surrounding MSCs. Using RT(2)-PCR and western blots, we demonstrate that a proportion of HPCs maintained the expression of CD34 throughout a culture period of 14 days. In colony-forming unit assays, the hematopoietic stem cell plasticity remained similar after 14 days of bioreactor co-culture, whereas monolayer co-cultures showed increasing signs of HPC differentiation and loss of stemness. These data support the notion that the 3D microenvironment created within the microcavity array preserves vital stem cell functions of HPCs more efficiently than conventional co-culture systems. PMID:26829941

  18. Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction

    OpenAIRE

    Minuth, Will W.; Denk, Lucia

    2016-01-01

    Abstract Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of...

  19. 角膜缘干细胞龛的概念及其研究进展%Evolving concepts on limbal stem cells and their niche

    Institute of Scientific and Technical Information of China (English)

    郑天玉; 徐建江

    2008-01-01

    干细胞龛是成体干细胞的集中存储部位,通过特定的细胞外基质和龛细胞提供特殊的微环境,对维持干细胞的高增殖力和诱导定向分化起关键作用.角膜缘干细胞(LSC)是目前公认的角膜上皮的成体干细胞,其相关理论基础与临床研究发展迅速,但是,目前对LSC龛的了解略显滞后.本文对LSC龛在角膜缘上皮小囊结构的定位;龛环境中血清源性和基质细胞源性细胞因子引发LSC胞内特定的信息通路;受损的角膜缘龛环境影响LSC的存活和功能以及LSC体外培养中通过羊膜载体重建龛环境等重要问题进行归纳,分析了LSC龛的研究现状.%As a concentrated location for adult somatic stem cells, the niche plays a crucial role on maintaining the high proliferative ability and the inducing the particular differentiation of the stem cells by providing the special microcnvironment containing definite extracellular matrix and niche cells. Nowadays limbal stem cells (LSCs) are the acknowledged adult somatic stem cells of corneal epithelium. Rapid progress has been accomplished in the theory and clinical practice on LSCs. However, the understanding on its niche has obviously fallen behind. This review summarized and analyzed the status quo of the study on niche of LSCs, mainly through the following aspects: the precise location of the niche was described as limbal epithelial crypts; the blood-derived and stroma-derived cytokine could regulate the proliferation,differentiation and apoptosis of LSCs by triggering particular intracellular information pathway; the survival and function of LSCs could be influenced by damaged niche microenvironment, while the differentiation of LSCs could be veered by another type of niche; in ex vivo LSCs expansion, reconstruction of the niche is needed and could be achieved by 3T3 cells or using amniotic membrane as the carrier.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

  2. Targeting the molecular and cellular interactions of the bone marrow niche in immunologic disease.

    Science.gov (United States)

    Brozowski, Jaime M; Billard, Matthew J; Tarrant, Teresa K

    2014-02-01

    Recent investigations have expanded our knowledge of the regulatory bone marrow (BM) niche, which is critical in maintaining and directing hematopoietic stem cell (HSC) self-renewal and differentiation. Osteoblasts, mesenchymal stem cells (MSCs), and CXCL12-abundant reticular (CAR) cells are niche components in close association with HSCs and have been more clearly defined in immune cell function and homeostasis. Importantly, cellular inhabitants of the BM niche signal through G protein-coupled surface receptors (GPCRs) for various appropriate immune functions. In this article, recent literature on BM niche inhabitants (HSCs, osteoblasts, MSCs, CAR cells) and their GPCR mechanistic interactions are reviewed for better understanding of the BM cells involved in immune development, immunologic disease, and current immune reconstitution therapies. PMID:24408534

  3. 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.

  4. Exosomes as Novel Regulators of Adult Neurogenic Niches

    Science.gov (United States)

    Bátiz, Luis Federico; Castro, Maite A.; Burgos, Patricia V.; Velásquez, Zahady D.; Muñoz, Rosa I.; Lafourcade, Carlos A.; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2016-01-01

    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 (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). 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 (CSF) 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. Advance of study on cancer stem cell niche%肿瘤干细胞niche的研究进展

    Institute of Scientific and Technical Information of China (English)

    徐皓; 林志雄

    2010-01-01

    Cancer stem cell niche provides a relatively stable microenvironment for cancer stem cell (CSC)existence,proliferation and differentiation.This microenvironment consists of kinds of cells,stroma and cytokines, etc. Within it , CSC can resist chemoradiotherapy. It has been shown that destruction of the microen vironment can significantly enhance the effect of chemoradiotherapy and improve prognosis of cancer patients.%肿瘤干细胞niche为肿瘤干细胞生存以及增殖分化提供了相对稳定的微环境,这一微环境由各种细胞、基质以及多种细胞因子等构成.在这一微环境中,肿瘤干细胞能够耐受放化疗.文献报道,破坏这种微环境能显著增强放化疗效果,从而改善肿瘤患者的预后.

  9. 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.

  10. Stem Cell Interaction with Somatic Niche May Hold the Key to Fertility Restoration in Cancer Patients

    OpenAIRE

    Deepa Bhartiya; Kalpana Sriraman; Seema Parte

    2012-01-01

    The spontaneous return of fertility after bone marrow transplantation or heterotopic grafting of cryopreserved ovarian cortical tissue has surprised many, and a possible link with stem cells has been proposed. We have reviewed the available literature on ovarian stem cells in adult mammalian ovaries and presented a model that proposes that the ovary harbors two distinct populations of stem cells, namely, pluripotent, quiescent, very small embryonic-like stem cells (VSELs), and slightly larger...

  11. Kinetic modeling reveals a common death niche for newly formed and mature B cells.

    Directory of Open Access Journals (Sweden)

    Gitit Shahaf

    Full Text Available BACKGROUND: B lymphocytes are subject to elimination following strong BCR ligation in the absence of appropriate second signals, and this mechanism mediates substantial cell losses during late differentiation steps in the bone marrow and periphery. Mature B cells may also be eliminated through this mechanism as well as through normal turnover, but the population containing mature cells destined for elimination has not been identified. Herein, we asked whether the transitional 3 (T3 subset, which contains most newly formed cells undergoing anergic death, could also include mature B cells destined for elimination. METHODOLOGY/PRINCIPAL FINDINGS: To interrogate this hypothesis and its implications, we applied mathematical models to previously generated in vivo labeling data. Our analyses reveal that the death rate of T3 B cells is far higher than the death rates of all other splenic B cell subpopulations. Further, the model, in which the T3 pool includes both newly formed and mature primary B cells destined for apoptotic death, shows that this cell loss may account for nearly all mature B cell turnover. CONCLUSIONS/SIGNIFICANCE: This finding has implications for the mechanism of normal mature B cell turnover.

  12. 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.

  13. Three-Dimensional Gastrointestinal Organoid Culture in Combination with Nerves or Fibroblasts: A Method to Characterize the Gastrointestinal Stem Cell Niche.

    Science.gov (United States)

    Pastuła, Agnieszka; Middelhoff, Moritz; Brandtner, Anna; Tobiasch, Moritz; Höhl, Bettina; Nuber, Andreas H; Demir, Ihsan Ekin; Neupert, Steffi; Kollmann, Patrick; Mazzuoli-Weber, Gemma; Quante, Michael

    2016-01-01

    The gastrointestinal epithelium is characterized by a high turnover of cells and intestinal stem cells predominantly reside at the bottom of crypts and their progeny serve to maintain normal intestinal homeostasis. Accumulating evidence demonstrates the pivotal role of a niche surrounding intestinal stem cells in crypts, which consists of cellular and soluble components and creates an environment constantly influencing the fate of stem cells. Here we describe different 3D culture systems to culture gastrointestinal epithelium that should enable us to study the stem cell niche in vitro in the future: organoid culture and multilayered systems such as organotypic cell culture and culture of intestinal tissue fragments ex vivo. These methods mimic the in vivo situation in vitro by creating 3D culture conditions that reflect the physiological situation of intestinal crypts. Modifications of the composition of the culture media as well as coculturing epithelial organoids with previously described cellular components such as myofibroblasts, collagen, and neurons show the impact of the methods applied to investigate niche interactions in vitro. We further present a novel method to isolate labeled nerves from the enteric nervous system using Dclk1-CreGFP mice. PMID:26697073

  14. Three-Dimensional Gastrointestinal Organoid Culture in Combination with Nerves or Fibroblasts: A Method to Characterize the Gastrointestinal Stem Cell Niche

    Directory of Open Access Journals (Sweden)

    Agnieszka Pastuła

    2016-01-01

    Full Text Available The gastrointestinal epithelium is characterized by a high turnover of cells and intestinal stem cells predominantly reside at the bottom of crypts and their progeny serve to maintain normal intestinal homeostasis. Accumulating evidence demonstrates the pivotal role of a niche surrounding intestinal stem cells in crypts, which consists of cellular and soluble components and creates an environment constantly influencing the fate of stem cells. Here we describe different 3D culture systems to culture gastrointestinal epithelium that should enable us to study the stem cell niche in vitro in the future: organoid culture and multilayered systems such as organotypic cell culture and culture of intestinal tissue fragments ex vivo. These methods mimic the in vivo situation in vitro by creating 3D culture conditions that reflect the physiological situation of intestinal crypts. Modifications of the composition of the culture media as well as coculturing epithelial organoids with previously described cellular components such as myofibroblasts, collagen, and neurons show the impact of the methods applied to investigate niche interactions in vitro. We further present a novel method to isolate labeled nerves from the enteric nervous system using Dclk1-CreGFP mice.

  15. Synergistic role of three dimensional niche and hypoxia on conservation of cancer stem cell phenotype.

    Science.gov (United States)

    Gorgun, Cansu; Ozturk, Sukru; Gokalp, Sevtap; Vatansever, Seda; Gurhan, S Ismet Deliloglu; Urkmez, Aylin Sendemir

    2016-09-01

    Hypoxia is a pathalogical condition in which tissues are deprived of adequate oxygen supply. The hypoxia effect on tumors has a critically important role on maintenance of cancer stem cell phenotype. The aim of this study is to investigate the effects of hypoxia on cancer stem cells on three dimensional (3D) in vitro culture models. Osteosarcoma stem cells characterized by CD133 surface protein were isolated from osteosarcoma cell line (SaOS-2) by magnetic-activated cell sorting (MACS) technique. Isolated CD133(+) and CD133(-) cells were cultivated under hypoxic (1% O2) and normoxic conditions (21% O2) for 3 days. For the 3D model, bacterial cellulose scaffold was used as the culture substrate. 3D morphologies of cells were examined by scanning electron microscopy (SEM); RT-PCR and immunocytochemistry staining were used to demonstrate conservation of the cancer stem cell phenotype in 3D environment under hypoxic conditions. Cell viability was shown by MTT assay on 3. and 7. culture days. This study is seen as an introduction to develop a 3D hypoxic cancer stem cell based tumor model to study CSC behavior and tumor genesis in vitro. PMID:26718870

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

    OpenAIRE

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

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

    OpenAIRE

    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 be...

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

    OpenAIRE

    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 be...

  19. 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

  20. Decidualization induces a secretome switch in perivascular niche cells of the human endometrium.

    Science.gov (United States)

    Murakami, Keisuke; Lee, Yie Hou; Lucas, Emma S; Chan, Yi-Wah; Durairaj, Ruban Peter; Takeda, Satoru; Moore, Jonathan D; Tan, Bee K; Quenby, Siobhan; Chan, Jerry K Y; Gargett, Caroline E; Brosens, Jan J

    2014-11-01

    The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5(+)) and nonperivascular (W5C5(-)) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5(+):W5C5(-) cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5(+) progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5(+)-derived cells produced lower levels of various chemokines and inflammatory modulators when compared with their W5C5(-) counterparts. This divergence in secretomes was switched and became more pronounced upon decidualization, which transformed perivascular W5C5(+) cells into the dominant source of a range of chemokines and cytokines, including leukemia inhibitory factor and chemokine (C-C motif) ligand 7. Our findings suggest that the decidual response is spatially organized at the embryo-maternal interface with differentiating perivascular cells establishing distinct cytokine and chemokine profiles that could potentially direct trophoblast toward maternal vessels and govern local immune responses in pregnancy. PMID:25116707

  1. Organoids: Modeling Development and the Stem Cell Niche in a Dish.

    Science.gov (United States)

    Kretzschmar, Kai; Clevers, Hans

    2016-09-26

    Organoids are three-dimensional in-vitro-grown cell clusters with near-native microanatomy that arise from self-organizing mammalian pluripotent or adult stem cells. Although monolayer stem cell cultures were established more than 40 years ago, organoid technology has recently emerged as an essential tool for both fundamental and biomedical research. For developmental biologists, organoids provide powerful means for ex vivo modeling of tissue morphogenesis and organogenesis. Here we discuss how organoid cultures of the intestine and other tissues have been established and how they are utilized as an in vitro model system for stem cell research and developmental biology. PMID:27676432

  2. 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

  3. Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche

    International Nuclear Information System (INIS)

    Highlights: ► We established a 3D culture system to allow long-term culture of stomach cells. ► In this culture system, gastric epithelial cells grew for about 3 months. ► The cultured cells differentiated into multi-units of the stomach. ► This culture method should be useful for elucidating the cause of gastric diseases. -- Abstract: Compared to the small intestine and colon, little is known about stem cells in the stomach because of a lack of specific stem cell markers and an in vitro system that allows long-term culture. Here we describe a long-term three-dimensional (3D) primary gastric culture system within the stem cell niche. Glandular stomach cells from neonatal mice cultured in collagen gel yielded expanding sphere-like structures for 3 months. The wall of the gastrospheres consisted of a highly polarized epithelial monolayer with an outer lining of myofibroblasts. The epithelial cells showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm as well as expression of MUC5AC, indicating differentiation into gastric surface mucous cells. These cells demonstrated the features of fully differentiated gastric surface mucous cells such as microvilli, junctional complexes, and glycogen and secretory granules. Fewer than 1% of cultured epithelial cells differentiated into enteroendocrine cells. Active proliferation of the epithelial cells and many apoptotic cells in the inner lumen revealed the rapid cell turnover in gastrospheres in vitro. This method enables us to investigate the role of signaling between cell–cell and epithelial–mesenchymal interactions in an environment that is extremely similar to the in vivo environment

  4. Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche

    Energy Technology Data Exchange (ETDEWEB)

    Katano, Takahito [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Ootani, Akifumi [Department of Gastroenterology and GI Endoscopy Center, Shin-Kokura Hospital, Federation of National Public Service Personnel Mutual Aid Associations, 1-3-1 Kanada, Kokurakita-ku, Kitakyushu 803-0816 (Japan); Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501 (Japan); Mizoshita, Tsutomu, E-mail: tmizoshi@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Tanida, Satoshi; Tsukamoto, Hironobu; Ozeki, Keiji; Ebi, Masahide; Mori, Yoshinori; Kataoka, Hiromi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Toda, Shuji [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501 (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-03-22

    Highlights: ► We established a 3D culture system to allow long-term culture of stomach cells. ► In this culture system, gastric epithelial cells grew for about 3 months. ► The cultured cells differentiated into multi-units of the stomach. ► This culture method should be useful for elucidating the cause of gastric diseases. -- Abstract: Compared to the small intestine and colon, little is known about stem cells in the stomach because of a lack of specific stem cell markers and an in vitro system that allows long-term culture. Here we describe a long-term three-dimensional (3D) primary gastric culture system within the stem cell niche. Glandular stomach cells from neonatal mice cultured in collagen gel yielded expanding sphere-like structures for 3 months. The wall of the gastrospheres consisted of a highly polarized epithelial monolayer with an outer lining of myofibroblasts. The epithelial cells showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm as well as expression of MUC5AC, indicating differentiation into gastric surface mucous cells. These cells demonstrated the features of fully differentiated gastric surface mucous cells such as microvilli, junctional complexes, and glycogen and secretory granules. Fewer than 1% of cultured epithelial cells differentiated into enteroendocrine cells. Active proliferation of the epithelial cells and many apoptotic cells in the inner lumen revealed the rapid cell turnover in gastrospheres in vitro. This method enables us to investigate the role of signaling between cell–cell and epithelial–mesenchymal interactions in an environment that is extremely similar to the in vivo environment.

  5. Realized niche width of a brackish water submerged aquatic vegetation under current environmental conditions and projected influences of climate change.

    Science.gov (United States)

    Kotta, Jonne; Möller, Tiia; Orav-Kotta, Helen; Pärnoja, Merli

    2014-12-01

    Little is known about how organisms might respond to multiple climate stressors and this lack of knowledge limits our ability to manage coastal ecosystems under contemporary climate change. Ecological models provide managers and decision makers with greater certainty that the systems affected by their decisions are accurately represented. In this study Boosted Regression Trees modelling was used to relate the cover of submerged aquatic vegetation to the abiotic environment in the brackish Baltic Sea. The analyses showed that the majority of the studied submerged aquatic species are most sensitive to changes in water temperature, current velocity and winter ice scour. Surprisingly, water salinity, turbidity and eutrophication have little impact on the distributional pattern of the studied biota. Both small and large scale environmental variability contributes to the variability of submerged aquatic vegetation. When modelling species distribution under the projected influences of climate change, all of the studied submerged aquatic species appear to be very resilient to a broad range of environmental perturbation and biomass gains are expected when seawater temperature increases. This is mainly because vegetation develops faster in spring and has a longer growing season under the projected climate change scenario. PMID:24933438

  6. 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.

  7. GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

    OpenAIRE

    Young, Stephanie Z.; Bordey, Angélique

    2009-01-01

    Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery tha...

  8. 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.

  9. Tubular solid oxide fuel cell current collector

    Science.gov (United States)

    Bischoff, Brian L.; Sutton, Theodore G.; Armstrong, Timothy R.

    2010-07-20

    An internal current collector for use inside a tubular solid oxide fuel cell (TSOFC) electrode comprises a tubular coil spring disposed concentrically within a TSOFC electrode and in firm uniform tangential electrical contact with the electrode inner surface. The current collector maximizes the contact area between the current collector and the electrode. The current collector is made of a metal that is electrically conductive and able to survive under the operational conditions of the fuel cell, i.e., the cathode in air, and the anode in fuel such as hydrogen, CO, CO.sub.2, H.sub.2O or H.sub.2S.

  10. 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.

  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. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system.

    Science.gov (United States)

    Konradt, Christoph; Ueno, Norikiyo; Christian, David A; Delong, Jonathan H; Pritchard, Gretchen Harms; Herz, Jasmin; Bzik, David J; Koshy, Anita A; McGavern, Dorian B; Lodoen, Melissa B; Hunter, Christopher A

    2016-01-01

    An important function of the blood-brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood-brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature. The use of diverse transgenic parasites combined with reporter mice and intravital imaging demonstrated that replication in and lysis of endothelial cells precedes invasion of the central nervous system, and highlight a novel mechanism for parasite entry to the central nervous system. PMID:27572166

  13. Cholangiocarcinoma Stem-like Cells Shapes Tumor-initiating Niche by Regulating Associated Macrophages

    DEFF Research Database (Denmark)

    Raggi, Chiara; Correnti, Margherita; Sica, Antonio;

    2016-01-01

    -SPHs were highly enriched for CSC, liver cancer and embryonic stem cell markers both at gene and protein levels. Next, FACS-analysis showed that in presence of CCA-SPH-CM, CD14+ expressed key macrophage (MØ) markers (CD68, CD115, HLA-DR, CD206) indicating that CCA-SPH- conditioned medium was a strong MØ...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. 脊髓神经干细胞Niche的研究进展%Research progress in spinal cord neural stem cell Niche

    Institute of Scientific and Technical Information of China (English)

    廖法学; 张辉; 尹宗生

    2012-01-01

    BACKGROUND: Spinal cord injury is a common orthopedic disease. A lot of work has been done to focus on neural stem cells for treating spinal cord injury. The effect of spinal cord neural stem cell Niche on neural stem cells has become a gradually increasing research area.OBJECTIVE: To summarize the related research progress in spinal cord neural stem cell Niche.METHODS: A computer-based online search of Pubmed (1980-01/2011-11) and CNKI (2003-01/2011-11) was performed for articles in English and Chinese respectively with the keywords "neural stem cells, niche/microenvironment, spinal cord". In addition, manual search was performed.RESULTS AND CONCLUSION: A total of 483 articles were obtained, and finally 31 articles were included. The Niche provides a relatively stable microenvironment for survival, self-renewal and differentiation of spinal cord neural stem cells. After spinal cord injury, the change of Niche plays an important impact on the fate of spinal cord neural stem cells. Understanding the research progress of spinal cord neural stem cell Niche would provide a theoretical basis for treatment of spinal cord injury using neural stem cells.%背景:脊髓损伤是临床上常见的骨科疾病,大量工作聚焦于神经干细胞治疗脊髓损伤的研究上,脊髓神经干细胞Niche对神经干细胞的作用成为了新的热点.目的:综述脊髓神经干细胞Niche的相关研究进展.方法:应用计算机检索PubMed 1980-01/2011-11期间的相关文章,检索词为"neural stem cells,niche/microenvironment,spinal cord",并限定文章语言种类为English.同时计算机检索中国期刊全文数据库2003-01/2011-11 期间的相关文章,检索词为"神经干细胞,微环境,脊髓损伤",并限定文章语言种类为中文.此外还手工查阅相关专著数部.结果与结论:共检索到文献483篇,最终纳入31 篇.脊髓神经干细胞Niche为脊髓神经干细胞生存、自我更新以及分化提供了相对稳定的微环境,脊髓

  18. Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes.

    Science.gov (United States)

    Newell, Evan W; Sigal, Natalia; Bendall, Sean C; Nolan, Garry P; Davis, Mark M

    2012-01-27

    Cytotoxic CD8(+) T lymphocytes directly kill infected or aberrant cells and secrete proinflammatory cytokines. By using metal-labeled probes and mass spectrometric analysis (cytometry by time-of-flight, or CyTOF) of human CD8(+) T cells, we analyzed the expression of many more proteins than previously possible with fluorescent labels, including surface markers, cytokines, and antigen specificity with modified peptide-MHC tetramers. With 3-dimensional principal component analysis (3D-PCA) to display phenotypic diversity, we observed a relatively uniform pattern of variation in all subjects tested, highlighting the interrelatedness of previously described subsets and the continuous nature of CD8(+) T cell differentiation. These data also showed much greater complexity in the CD8(+) T cell compartment than previously appreciated, including a nearly combinatorial pattern of cytokine expression, with distinct niches occupied by virus-specific cells. This large degree of functional diversity even between cells with the same specificity gives CD8(+) T cells a remarkable degree of flexibility in responding to pathogens. PMID:22265676

  19. Biological properties of spermatogonial stem cell niches%精原干细胞微环境的生物学特性

    Institute of Scientific and Technical Information of China (English)

    李玲玲; 刘洋; 金波

    2012-01-01

    成体干细胞的自我更新和分化与其微环境关系密切.精原干细胞(spermatogonial stem cells,SSCs)是体内自然状态下唯一能将遗传信息传至子代的成体干细胞.探讨SSCs更新和分化的调控机制有助于精子发生机理的阐明,并为探究其他成体干细胞增殖分化的调节机制提供依据.因此,SSCs系统为成体干细胞微环境研究提供了理想模型.资料表明,SSCs的更新和分化受其微环境的调控.基于本室的工作,参考最新文献,本文主要从SSCs微环境的基本特性、构成及其产生的各种调控因子等角度,评述了SSCs微环境的生物学特性及其与SSCs更新和分化间的关系,以期为本领域研究及其他成体干细胞相关研究提供借鉴.%The self-renewal and differentiation of adult stem cells are closely related to their niches. Naturally, spermatogonial stem cells (SSCs) are the only adult stem cells in the body, which can transfer genetic information into the offspring. An insight into the modulation of the self-renewal and differentiation of SSCs can help elucidate the mechanisms of spermatogenesis and investigate the proliferation and differentiation of other adult stem cells. Therefore, the SSC system provides an ideal model for researches on the adult stem cell niche. More and more evidence indicates that the self-renewal and differentiation of SSCs are regulated by their niches. Based on our previous work and other related findings recently reported, this article presents an overview on the biological properties of SSC niches and their relationship with the self-renewal and differentiation of SSCs, focusing on the basic properties and components of SSC niches and various regulatory factors they produce.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Improved micromorph tandem cell performance through enhanced top cell currents

    Energy Technology Data Exchange (ETDEWEB)

    Platz, R.; Vaucher, N.P.; Fischer, D.; Meier, J.; Shah, A. [Univ. de Neuchatel (Switzerland). Inst. de Microtechnique

    1997-12-31

    Two approaches to increasing the current in the amorphous silicon top cell of an amorphous silicon/microcrystalline silicon (a-Si:H/{micro}c-Si:H) tandem cell are presented. The goal is to raise the stabilized efficiency of such cells. The deposition of the amorphous top cell at higher than standard substrate temperature is shown to reduce the optical gap of the i-layer and to increase the current which is generated with a given i-layer thickness. Furthermore, a selectively reflecting ZnO interface layer between the component cells is presented as a viable tool for enhancing the current generation in the top cell by selective reflection of light. The authors present a micromorph tandem cell containing the amorphous top cell deposited at high substrate temperature, and additionally the ZnO mirror layer. A top cell thickness of 150 nm is shown to be sufficient to provide a current density of 13mA/cm{sup 2} in the top cell. Finally, the influence of such thin top cells on the stabilized efficiency of the tandem cell is investigated by experiment and by means of semi-empirical modeling. Model and experiment confirm that such reduced-gap top cells, together with current enhancement due to the mirror layer, have a high potential for improving the stabilized efficiency of micromorph tandem cells.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Research Progress of Spermatogonial Stem Cells Niche%精原干细胞niche的研究进展

    Institute of Scientific and Technical Information of China (English)

    李靳; 彭奔; 刘苗苗; 邓丽丽; 张长城

    2015-01-01

    精原干细胞(spermatogonial stem cells,SSCs)是指睾丸内位于曲精细管基膜上既能自我更新维持自身适量恒定,又能定向分化产生精母细胞的一类原始精原细胞.随着干细胞深入的研究,人们发现了一种控制着干细胞可塑性与命运的微环境,此微环境被称为干细胞niche,干细胞niche由niche细胞、细胞外基质、细胞因子等构成.精原干细胞niche是由黏附因子、生长因子、支持细胞、间质细胞以及小管周肌肉细胞组成.大量的研究表明支持细胞在睾丸中是主要的成体细胞,通过分泌可溶性的因子来影响精原干细胞niche的结构与功能,同时支持细胞还能够间接的影响其他的成体细胞.随着年龄的增长使得精原干细胞niche的功能下降.精原干细胞数量以及精原干细胞niche为我们研究组织特异性干细胞生物学以及保持再生组织平衡提供了很宝贵的线索,精原干细胞对于保持组织的自我更新具有很重要的作用,并且受到人们大量的关注,然而精原干细胞niche也起到很重要的作用,它为治疗一些疾病提供新途径.本文将综述精原干细胞niche及其变化对精原干细胞功能调节的相关研究进展.

  10. 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.

  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. PMID:17901404

  12. 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

  13. The endoderm specifies the mesodermal niche for the germline in Drosophila via Delta-Notch signaling

    OpenAIRE

    Okegbe, Tishina C.; DiNardo, Stephen

    2011-01-01

    Interactions between niche cells and stem cells are vital for proper control over stem cell self-renewal and differentiation. However, there are few tissues where the initial establishment of a niche has been studied. The Drosophila testis houses two stem cell populations, which each lie adjacent to somatic niche cells. Although these niche cells sustain spermatogenesis throughout life, it is not understood how their fate is established. Here, we show that Notch signaling is necessary to spec...

  14. 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

  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.

    2016-01-01

    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. PMID:26675257

  16. 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 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......, decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts......BACKGROUND: The tumor microenvironment plays a determinative role in stimulating tumor progression and metastasis. Notably, tumor-stroma signals affect the pattern of infiltrated immune cells and the profile of tumor-released cytokines. Among the known molecules that are engaged in stimulating...

  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. 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.

    2015-01-01

    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. PMID:26409016

  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. From blood to brain: the neurogenic niche of the crayfish brain.

    Science.gov (United States)

    Hartenstein, Volker

    2014-08-11

    Adult neurogenic niches are present in both vertebrates and invertebrates. Where do stem cells populating these niches originate, and what are the mechanisms maintaining their self-renewal? In this issue of Developmental Cell, Benton et al. (2014) show that in crayfish, hemolymph-derived cells enter a neurogenic niche to replenish neural progenitors. PMID:25117680

  1. Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction.

    Science.gov (United States)

    Minuth, Will W; Denk, Lucia

    2016-01-01

    Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of specimens by glutaraldehyde (GA) solution including cupromeronic blue, ruthenium red, or tannic acid for electron microscopy depicts that the interface is not void but filled in extended areas by textured extracellular matrix. Surprisingly, projections of mesenchymal cells cross the interface to contact epithelial cells. At those sites the plasma membranes of a mesenchymal and an epithelial cell are connected via tunneling nanotubes. Regarding detected morphological features in combination with involved morphogens, their transport cannot longer be explained solely by diffusion. Instead, it has to be sorted according to biophysical properties of morphogens and to detected environment. Thus, the new working hypothesis is that morphogens with good solubility such as glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factors (FGFs) are transported by diffusion. Morphogens with minor solubility such as bone morphogenetic proteins (BMPs) are secreted and stored for delivery on demand in illustrated extracellular matrix. In contrast, morphogens with poor solubility such as Wnts are transported in mesenchymal cell projections along the plasma membrane or via illustrated tunneling nanotubes. However, the presence of an intercellular route between mesenchymal and epithelial stem/progenitor cells by tunneling nanotubes also makes it possible that all morphogens are transported this way. PMID:26862472

  2. Can Niche Agriculturalists Take Notes from the Craft Beer Industry?

    OpenAIRE

    Woolverton, Andrea E.; Parcell, Joseph L.

    2008-01-01

    This industry-level case study focuses on the growth cycles of craft brewing, a niche industry. The research case is defined as the craft beer industry evolution including the surrounding institutional and consumer environments. The research goal is to provide insight for niche agriculturalists by examining the case of the successful niche craft beer industry. First, the environment surrounding craft beer reemergence is analyzed. We examine the current state of the craft beer industry with a ...

  3. The oncometabolite R-2-hydroxyglutarate activates NF-κB-dependent tumor-promoting stromal niche for acute myeloid leukemia cells.

    Science.gov (United States)

    Chen, Jing-Yi; Lai, You-Syuan; Tsai, Hui-Jen; Kuo, Cheng-Chin; Yen, B Linju; Yeh, Su-Peng; Sun, H Sunny; Hung, Wen-Chun

    2016-01-01

    Mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 in acute myeloid leukemia (AML) cells produce the oncometabolite R-2-hydroxyglutarate (R-2HG) to induce epigenetic alteration and block hematopoietic differentiation. However, the effect of R-2HG released by IDH-mutated AML cells on the bone marrow microenvironment is unclear. Here, we report that R-2HG induces IκB kinase-independent activation of NF-κB in bone marrow stromal cells. R-2HG acts via a reactive oxygen species/extracellular signal-regulated kinase (ERK)-dependent pathway to phosphorylate NF-κB on the Thr254 residue. This phosphorylation enhances the interaction of NF-κB and the peptidyl-prolyl cis-trans isomerase PIN1 and increases the protein stability and transcriptional activity of NF-κB. As a consequence, R-2HG enhances NF-κB-dependent expression of cytokines including IL-6, IL-8 and complement 5a to stimulate proliferation of AML cells. In addition, R-2HG also upregulates vascular endothelial adhesion molecule 1 and CXCR4 in stromal cells to enhance the contact between AML and stromal cells and attenuates chemotherapy-induced apoptosis. More importantly, we validated the R-2HG-activated gene signature in the primary bone marrow stromal cells isolated from IDH-mutated AML patients. Collectively, our results suggest that AML cell-derived R-2HG may be helpful for the establishment of a supportive bone marrow stromal niche to promote AML progression via paracrine stimulation. PMID:27577048

  4. A niche for neutrality.

    Science.gov (United States)

    Adler, Peter B; Hillerislambers, Janneke; Levine, Jonathan M

    2007-02-01

    Ecologists now recognize that controversy over the relative importance of niches and neutrality cannot be resolved by analyzing species abundance patterns. Here, we use classical coexistence theory to reframe the debate in terms of stabilizing mechanisms (niches) and fitness equivalence (neutrality). The neutral model is a special case where stabilizing mechanisms are absent and species have equivalent fitness. Instead of asking whether niches or neutral processes structure communities, we advocate determining the degree to which observed diversity reflects strong stabilizing mechanisms overcoming large fitness differences or weak stabilization operating on species of similar fitness. To answer this question, we propose combining data on per capita growth rates with models to: (i) quantify the strength of stabilizing processes; (ii) quantify fitness inequality and compare it with stabilization; and (iii) manipulate frequency dependence in growth to test the consequences of stabilization and fitness equivalence for coexistence. PMID:17257097

  5. 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.

  6. The prostate cancer bone marrow niche: more than just ‘fertile soil'

    OpenAIRE

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

    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 microenvironment 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 som...

  7. 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

  8. Teachers Unions in Turbulent Times: Maintaining Their Niche

    Science.gov (United States)

    Young, Tamara V.

    2011-01-01

    Drawing on niche theory, I describe the resource dimensions that compose teachers unions' niche and explain how aspects of the current political landscape buttress or undermine teachers unions' realization of those resources. I also discuss teachers unions' strategies to oppose any threats that undermine the realization of the resource arrays that…

  9. A hostel for the hostile: the bone marrow niche in hematologic neoplasms.

    Science.gov (United States)

    Krause, Daniela S; Scadden, David T

    2015-11-01

    Our understanding of the biology of the normal hematopoietic stem cell niche has increased steadily due to improved murine models and sophisticated imaging tools. Less well understood, but of growing interest, is the interaction between cells in the bone marrow during the initiation, maintenance and treatment of hematologic neoplasms. This review summarizes the emerging concepts of the normal and leukemic hematopoietic bone marrow niche. Furthermore, it reviews current models of how the microenvironment of the bone marrow may contribute to or be modified by leukemogenesis. Finally, it provides the rationale for a "two-pronged" approach, directly targeting cancer cells themselves while also targeting the bone microenvironment to make it inhospitable to malignant cells and, ultimately, eradicating cancer stem-like cells. PMID:26521296

  10. Functionally deficient mesenchymal stem cells reside in the bone marrow niche with M2-macrophages and amyloid-β protein adjacent to loose total joint implants.

    Science.gov (United States)

    Margulies, Bryan S; DeBoyace, Sean D; Parsons, Adrienne M; Policastro, Connor G; Ee, Jessica S S; Damron, Timothy S

    2015-05-01

    We sought to demonstrate whether there is a difference in the local mesenchymal stem cells (MSC) niche obtained from patients undergoing their first total joint replacement surgery versus those patients undergoing a revision surgery for an failing total joint implant. Bone marrow aspirates collected from patients undergoing revision total joint arthroplasty were observed to be less clonal and the expression of PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, and nucleostemin were decreased. Revision MSC were also less able to commit to an osteoblast-lineage or an adipocyte-lineage. Further, in revision MSC, OPG, and IL6 expression were increased. Monocytes, derived from revision whole marrow aspirates, were less capable of differentiating into osteoclasts, the cells implicated in the pathologic degradation of bone. Osteoclasts were also not observed in tissue samples collected adjacent to the implants of revision patients; however, the alternatatively activated M2-macrophage phenotype was observed in parallel with pathologic accumulations of amyloid-β, τ-protien and 3-nitrotyrosine. Despite the limited numbers of patients examined, our data suggest that nucleostemin may be a useful functional marker for MSC while the observation of M2-macrophage infiltration around the implant lays the foundation for future investigation into a novel mechanism that we propose is associated with loose total joint implants.

  11. 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.

  12. Current understanding concerning intestinal stem cells

    Science.gov (United States)

    Cui, Shuang; Chang, Peng-Yu

    2016-01-01

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  13. Current understanding concerning intestinal stem cells.

    Science.gov (United States)

    Cui, Shuang; Chang, Peng-Yu

    2016-08-21

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  14. NTPDase2 and Purinergic Signaling Control Progenitor Cell Proliferation in Neurogenic Niches of the Adult Mouse Brain

    OpenAIRE

    Gampe, Kristine; Stefani, Jennifer; Hammer, Klaus; Brendel, Peter; Pötzsch, Alexandra; Enikolopov, Grigori; Enjyoji, Keiichi; Acker-Palmer, Amparo; Robson, Simon C.; Zimmermann, Herbert

    2015-01-01

    Nerve cells are continuously generated from stem cells in the adult mammalian subventricular zone (SVZ) and hippocampal dentate gyrus. We have previously noted that stem/progenitor cells in the SVZ and the subgranular layer (SGL) of the dentate gyrus express high levels of plasma membrane-bound nucleoside triphosphate diphosphohydrolase 2 (NTPDase2), an ectoenzyme that hydrolyzes extracellular nucleoside di- and triphosphates. We inferred that deletion of NTPDase2 would increase local extrace...

  15. 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.

  16. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research.

    Science.gov (United States)

    Akhmanova, Maria; Osidak, Egor; Domogatsky, Sergey; Rodin, Sergey; Domogatskaya, Anna

    2015-01-01

    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID:26351461

  17. Testing and Characterization of Anode Current in Aluminum Reduction Cells

    Science.gov (United States)

    Wang, Yongliang; Tie, Jun; Sun, Shuchen; Tu, Ganfeng; Zhang, Zhifang; Zhao, Rentao

    2016-06-01

    Anode current is an important parameter in the aluminum reduction process, but to test the anode current accurately is difficult at present. This study tested the individual anode current using the fiber-optic current sensor. The testing results show that this method can effectively avoid the interference of the electromagnetic field, and the current is measured with high precision which error is less than 1 pct. In the paper, the test currents under different cell conditions, including anode changing, metal tapping, abnormal current, and anode effect, are investigated using the method of time-domain and frequency-domain analysis, and the simulation method is also combined to investigate the cell conditions. The results prove that different cell conditions will show different anode current characteristics, and the individual current can monitor the cell conditions, especially the localized cell conditions. Some abnormal cell conditions can be found through anode current rather than cell voltage. The anode current can also be used for early detection of anode effect.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Paneth Cell-Rich Regions Separated by a Cluster of Lgr5+ Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche.

    Science.gov (United States)

    Langlands, Alistair J; Almet, Axel A; Appleton, Paul L; Newton, Ian P; Osborne, James M; Näthke, Inke S

    2016-06-01

    The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission. PMID:27348469

  5. Adipose-derived stem cells from lean and obese humans show depot specific differences in their stem cell markers, exosome contents and senescence: role of protein kinase C delta (PKCδ) in adipose stem cell niche

    Science.gov (United States)

    Patel, Rekha S.; Carter, Gay; El Bassit, Ghattas; Patel, Achintya A.; Cooper, Denise R.; Murr, Michel

    2016-01-01

    Background Adipose-derived stem cells (ASC) and its exosomes are gaining utmost importance in the field of regenerative medicine. The ASCs tested for their potential in wound healing are predominantly derived from the subcutaneous depot of lean donors. However, it is important to characterize the ASC derived from different adipose depots as these depots have clinically distinct roles. Methods We characterized the ASC derived from subcutaneous and omental depots from a lean donor (sc-ASCn and om-ASCn) and compared it to the ASC derived from an obese donor (sc-ASCo and om-ASCo) using flow cytometry and real time qPCR. Results We show that stem cell markers Oct4, Sal4, Sox15, KLF4 and BMI1 have distinct expression patterns in each ASC. We evaluated the secretome of the ASC and characterized their secreted exosomes. We show long noncoding RNAs (lncRNAs) are secreted by ASC and their expression varied between the ASC’s derived from different depots. Protein kinase C delta (PKCδ) regulates the mitogenic signals in stem cells. We evaluated the effect of silencing PKCδ in sc-ASCn, om-ASCn, sc-ASCo and om-ASCo. Using β-galactosidase staining, we evaluated the percentage of senescent cells in sc-ASCn, om-ASCn, sc-ASCo and om-ASCo. Our results also indicated that silencing PKCδ increases the percentage of senescent cells. Conclusions Our case-specific study demonstrates a role of PKCδ in maintaining the adipose stem cell niche and importantly demonstrates depot-specific differences in adipose stem cells and their exosome content. PMID:27358894

  6. Current Stem Cell Delivery Methods for Myocardial Repair

    OpenAIRE

    Sheng, Calvin C.; Li Zhou; Jijun Hao

    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 ske...

  7. 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...... with initial versus delayed radiotherapy. No survival differences in the larger study of the two studies were detected, which compared alternating with sequential delivery of radiotherapy (n = 335). The optimal way to deliver radiotherapy still must be defined. Two small, randomized studies on dose intensity...

  8. Femto Cells: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Khaled Elleithy

    2011-03-01

    Full Text Available This is a survey paper on the recently developed and rapidly evolving field of femtocells. Quite often, it isnoticed that cell-phone signals are strongly attenuated, when indoors, leading to call dropping or poor callquality. Femtocells are mini base stations that are deployed in users’ homes so that the user can directlyconnect to the cellular network through the femtocell instead of the outdoor macrocell, thereby increasingcall quality. In the later stages of the paper, we also discuss the integration of the femtocell into the 3Garchitecture, as well as the various interference issues that the femtocell faces.

  9. Current waveforms for pulse microdischarge inside dielectric cell

    International Nuclear Information System (INIS)

    Computer simulation for microplasma discharge inside coplanar dielectric cell was carried out via particles in cells (PiC) method. Discharge current waveforms have a shape of short pulses with length decreasing and maximum earlier appearance for larger voltages applied. Mostly ion current on the negative coplanar electrode has a smooth shape contrary to the mostly electron current on the positive one which has a sharp maximum at the end of electron avalanche. Address electrode current is significantly less than coplanar electrodes currents and has pulsations corresponding to the striation structures appearance.

  10. Current management of sickle cell anemia.

    Science.gov (United States)

    McGann, Patrick T; Nero, Alecia C; Ware, Russell E

    2013-08-01

    Proper management of sickle cell anemia (SCA) begins with establishing the correct diagnosis early in life, ideally during the newborn period. The identification of affected infants by neonatal screening programs allows early initiation of prophylactic penicillin and pneumococcal immunizations, which help prevent overwhelming sepsis. Ongoing education of families promotes the early recognition of disease-released complications, which allows prompt and appropriate medical evaluation and therapeutic intervention. Periodic evaluation by trained specialists helps provide comprehensive care, including transcranial Doppler examinations to identify children at risk for primary stroke, plus assessments for other parenchymal organ damage as patients become teens and adults. Treatment approaches that previously highlighted acute vaso-occlusive events are now evolving to the concept of preventive therapy. Liberalized use of blood transfusions and early consideration of hydroxyurea treatment represent a new treatment paradigm for SCA management. PMID:23709685

  11. Evidence of climatic niche shift during biological invasion.

    Science.gov (United States)

    Broennimann, O; Treier, U A; Müller-Schärer, H; Thuiller, W; Peterson, A T; Guisan, A

    2007-08-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk of introduction and establishment of newly or not-yet-introduced neophytes, but may not predict the full extent of invasions. PMID:17594425

  12. Evidence of climatic niche shift during biological invasion

    DEFF Research Database (Denmark)

    Broennimann, O.; Treier, Urs; Müller-Schärer, H.;

    2007-01-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche...... evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk...... in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical...

  13. The Fluctuation Niche in Plants

    International Nuclear Information System (INIS)

    Classical approaches to niche in coexisting plants have undervalued temporal fluctuations. We propose that fluctuation niche is an important dimension of the total niche and interacts with habitat and life-history niches to provide a better understanding of the multidimensional niche space where ecological interactions occur. To scale a fluctuation niche, it is necessary to relate environmental constrictions or species performance not only to the absolute values of the usual environmental and eco physiological variables but also to their variances or other measures of variability. We use Mediterranean plant communities as examples, because they present characteristic large seasonal and inter annual fluctuations in water and nutrient availabilities, along an episodic-constant gradient, and because the plant responses include a number of syndromes coupled to this gradient.

  14. Current overview on dental stem cells applications in regenerative dentistry

    Science.gov (United States)

    Bansal, Ramta; Jain, Aditya

    2015-01-01

    Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental stem cells were shortlisted and the facts are compiled. The objective of this review article is to discuss the history of stem cells, different stem cells relevant for dentistry, their isolation approaches, collection, and preservation of dental stem cells along with the current status of dental and medical applications. PMID:25810631

  15. 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...

  16. 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.

  17. 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.

  18. Stem Cell Niche and Its Roles in Proliferation and Differentiation of Stem Cells%干细胞niche及其在干细胞增殖分化中的作用

    Institute of Scientific and Technical Information of China (English)

    宋远会; 宋关斌

    2009-01-01

    干细胞(Stem cells)是一类具有自我更新和多向分化潜能的特殊细胞.在特定的条件下,干细胞可以增殖并分化为多种类型的细胞,但干细胞的增殖、分化行为高度依赖于其所处的生长小生态环境,即干细胞niche.干细胞与其niche之间通过相互的"时空对话"(Spatiotemporal dialog)实现自我更新和分化的平衡调控.本文对几种不同类型的niche及其与干细胞的相互关系做一简要介绍.

  19. 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.

  20. 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...

  1. 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)

  2. Monument og niche

    DEFF Research Database (Denmark)

    Juel-Christiansen, Carsten

    2009-01-01

    Introduktion til og uddrag af bogen: Monument og niche : den ny bys arkitektur / af Carsten Juel-Christiansen, 1985......Introduktion til og uddrag af bogen: Monument og niche : den ny bys arkitektur / af Carsten Juel-Christiansen, 1985...

  3. 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. PMID:23509740

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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. PMID:19500866

  9. 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.

  10. The niche of envy

    DEFF Research Database (Denmark)

    Quintanilla, Laura; Jensen de López, Kristine M.

    2013-01-01

    .g., socio-cultural, psychological, and anthropological research. Finally, in the third section, we introduce a cross-cultural and developmental view of how envy is embodied. We briefly address and offer a critique of Klein’s psychoanalytic view and present recent results from our cross-cultural studies of......Envy is the religion of the mediocre. It comforts them, it responds to the worries that gnaw at them and finally it rots their souls, allowing them to justify their meanings and their greed until they believe these to be virtues.—Carlos Ruiz Zafón “The niche of envy” is a cross-disciplinary attempt...... to capture and understand the complex and self-conscious emotion of envy as unfolded within social relationships and cultural settings. One of our main interests concerns how children come to understand envy in ontogenesis. Accordingly, we review existing theoretical approaches to understanding envy...

  11. 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.

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

    International Nuclear Information System (INIS)

    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 cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings

  13. Ontogenetic niche shifts in three Vaccinium species on a sub-alpine mountain side

    DEFF Research Database (Denmark)

    Auffret, A.G.; Meineri, E.; Bruun, Hans Henrik;

    2010-01-01

    Background: Climate warming in arctic and alpine regions is expected to result in the altitudinal migration of plant species, but current predictions neglect differences between species' regeneration niche and established niche. Aims: To examine potential recruitment of Vaccinium myrtillus, V...... recruitment in habitats at altitudes above its current populations. Conclusions: The potential for migration exists, but incongruence between regenerative and established niches presents a challenge for colonisers, as well as for plant migration modelling...

  14. 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.

  15. 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...

  16. Ionic currents in single isolated bullfrog atrial cells

    OpenAIRE

    1983-01-01

    Enzymatic dispersion has been used to yield single cells from segments of bullfrog atrium. Previous data (Hume and Giles, 1981) have shown that these individual cells are quiescent and have normal resting potentials and action potentials. The minimum DC space constant is approximately 920 microns. The major goals of the present study were: (a) to develop and refine techniques for making quantitative measurements of the transmembrane ionic currents, and (b) to identify the individual component...

  17. 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

  18. 肺转移瘤的转移前微环境与转移微环境%Pre-metastatic Niche and Metastatic Niche of Metastatic Lung Tumors

    Institute of Scientific and Technical Information of China (English)

    郑燕

    2011-01-01

    一个多世纪前Paget就肿瘤器官特异性转移现象提出了“种子与土壤”学说.时下研究热点集中在一些特殊因子介导的靶器官环境改造,肿瘤细胞归巢行为.有动物实验证实肺转移瘤形成前,肺部已发生大量炎症因子聚集.宿主靶器官的改变影响转移瘤形成的每一个步骤.Bethan Psaila与David Lyden针对这一土壤变化过程提出转移前微环境(pre-metastatic niche)及转移微环境(metastatic niche)假说,指出土壤的变化是转移瘤形成的保障.该假说提出后迅速引起肿瘤研究界轰动.研究这一系列细胞分子生物学的改变,有助于阐明肿瘤转移这一复杂的过程,为转移干预带来新的思路.%Steven Paget's "seed and soil" hypothesis for metastasis was a pivotal milestone in the study of malignant disease. Current views of cancer metastasis have centered on the intrinsic factors mediating preparation of the target organ and regulating the cell autonomous homing of tumor cells to the metastatic site. Many inflammatory cytokines in the lung provide an assembly platform for metastatic lesions, as shown by in vivo experimental models. New findings suggest that host cells within the target microenviroment play a key role in influencing each step of metastatic progression. Bethan Psaila and David Lyden have proposed a pre-metastatic niche and metastatic niche model to delineate the interactions of malignant cells with their microenvironment at the metastatic site. The niche model suggests that a suitably conducive microenvironment is essential in order for tumor cells to engraft and proliferate at secondary sites. It has quickly become the most influential hypothesis. Focusing on the cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to explain the events and to prevent metastasis at each step.

  19. 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. PMID:10117142

  20. Phylogenetic comparative approaches for studying niche conservatism

    OpenAIRE

    COOPER, NATALIE; Jetz, Walter; Freckleton, Rob P.

    2010-01-01

    Analyses of phylogenetic niche conservatism (PNC) are becoming increasingly common. However, each analysis makes subtly different assumptions about the evolutionary mechanism that generates patterns of niche conservatism. To understand PNC, analyses should be conducted with reference to a clear underlying model, using appropriate methods. Here, we outline five macroevolutionary models that may underlie patterns of PNC (drift, niche retention, phylogenetic inertia, niche filling ? shifti...

  1. Cell carriers for oncolytic viruses: current challenges and future directions.

    Science.gov (United States)

    Roy, Dominic G; Bell, John C

    2013-01-01

    The optimal route for clinical delivery of oncolytic viruses is thought to be systemic intravenous injection; however, the immune system is armed with several highly efficient mechanisms to remove pathogens from the circulatory system. To overcome the challenges faced in trying to delivery oncolytic viruses specifically to tumors via the bloodstream, carrier cells have been investigated to determine their suitability as delivery vehicles for systemic administration of oncolytic viruses. Cell carriers protect viruses from neutralization, one of the most limiting aspects of oncolytic virus interaction with the immune system. Cell carriers can also possess inherent tumor tropism, thus directing the delivery of the virus more specifically to a tumor. With preclinical studies already demonstrating the success and feasibility of this approach with multiple oncolytic viruses, clinical evaluation of cell-mediated delivery of viruses is on the horizon. Meanwhile, ongoing preclinical studies are aimed at identifying new cellular vehicles for oncolytic viruses and improving current promising cell carrier platforms. PMID:27512657

  2. Ecological niche of plant pathogens

    OpenAIRE

    Ecaterina Fodor

    2011-01-01

    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 ni...

  3. 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.

  4. 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.

  5. 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.

  6. Cytometry by Time-of-Flight Shows Combinatorial Cytokine Expression and Virus-Specific Cell Niches within a Continuum of CD8+ T Cell Phenotypes

    OpenAIRE

    Newell, Evan W; Sigal, Natalia; Bendall, Sean C.; Garry P Nolan; Davis, Mark M.

    2012-01-01

    Cytotoxic CD8+ T lymphocytes directly kill infected or aberrant cells and secrete proinflammatory cytokines. By using metal-labeled probes and mass spectrometric analysis (cytometry by time-of-flight, or CyTOF) of human CD8+ T cells, we analyzed the expression of many more proteins than previously possible with fluorescent labels, including surface markers, cytokines, and antigen specificity with modified peptide-MHC tetramers. With 3-dimensional principal component analysis (3D-PCA) to displ...

  7. Starting characteristics of direct current motors powered by solar cells

    Science.gov (United States)

    Singer, S.; Appelbaum, J.

    1989-01-01

    Direct current motors are used in photovoltaic systems. Important characteristics of electric motors are the starting to rated current and torque ratios. These ratios are dictated by the size of the solar cell array and are different for the various dc motor types. Discussed here is the calculation of the starting to rated current ratio and starting to rated torque ratio of the permanent magnet, and series and shunt excited motors when powered by solar cells for two cases: with and without a maximum-power-point-tracker (MPPT) included in the system. Comparing these two cases, one gets a torque magnification of about 3 for the permanent magnet motor and about 7 for other motor types. The calculation of the torques may assist the PV system designer to determine whether or not to include an MPPT in the system.

  8. Niche modelling of salt marsh plant species

    International Nuclear Information System (INIS)

    This study sought to extend the niche model of Spartina anglica to other salt marsh species, and to include tidal submergence in the models. The method used and preliminary data analysis are described. Tidal level and submergence niche models are examined, and niche width, niche overlap and species interaction are considered. Tidal level models and submergence niche models are compared for the 5 most common species. (UK)

  9. Hypothesis: The metastatic niche theory can elucidate infantile hemangioma development

    OpenAIRE

    Mihm, Martin C.; Nelson, J Stuart

    2010-01-01

    Recent advances in the understanding of the metastatic phenomenon in cancer have led to the description of a metastatic niche. This concept describes a site prepared for the tumor cells in areas frequently associated with metastasis for the individual tumor studied. This niche is a “soil” that allows for the tumor cell or “seed” to lodge and grow. Certain aspects of the biology of infantile hemangioma cells suggest a relationship to the placenta as a possible site of origin for the hemangioma...

  10. 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.

  11. 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.

  12. 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.

  13. 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. PMID:27547356

  14. Apoptosis by Direct Current Treatment in Tumor Cells and Tissues

    Science.gov (United States)

    Kim, Hongbae; Sim, Sungbo; Ahn, Saeyoung

    2003-10-01

    Electric field induces cell fusion, electroporation on biological cells, including apoptosis. Apoptosis is expressed in a series of natural enzymatic reactions for the natural elimination of unhealthy, genetically damaged, or otherwise aberrant cells that are not needed or not advantageous to the well-being of the organism. Its markers involve cell shrinkage, activation of intracellular caspase proteases, externalization of phosphatidylserine at the plasma membrane, and fragmentation of DNA. Direct electric fields using direct current have been exploited recently to investigate its effects on tumor cells and tissues, but the mechanism of direct electric fields has not been exhibited clearly other than by electroosmosis or pH changes. Direct electric field induces apoptosis in tumor cells cultured and tumor tissues as indicated by cell shrinkage, DNA fragmentation and tumor suppression. In our experiment that direct electric field was applied to tumor tissues via two needle electrodes inserted into tumor tissue 5mm at distance in parallel, pH changes resulted from electrochemical reaction, exhibiting about pH 9.0, 1.83, 2.0 in the vicinity of cathodic and anodic electrode, and at their mid-point, respectively. DNA fragmentation of tumor tissues destructed by direct electric field was analyzed by Tunel assay by ApopTag technology. As a result of this analysis, it showed that apoptosis in tumor tissue destructed was increased up to 59.1normal(control) tissues, showing 41.1, 31.1cathodic tissues. In vitro cell survival was exhibited that it was decreased with enhancing electric current intensity in the same condition of electrical charge 5C having different time applied. We will show results of apoptosis analyzed by flow cytometry in vitro.

  15. Quantifying the effect of electric current on cell adhesion studied by single-cell force spectroscopy.

    Science.gov (United States)

    Jaatinen, Leena; Young, Eleanore; Hyttinen, Jari; Vörös, János; Zambelli, Tomaso; Demkó, László

    2016-03-01

    This study presents the effect of external electric current on the cell adhesive and mechanical properties of the C2C12 mouse myoblast cell line. Changes in cell morphology, viability, cytoskeleton, and focal adhesion structure were studied by standard staining protocols, while single-cell force spectroscopy based on the fluidic force microscopy technology provided a rapid, serial quantification and detailed analysis of cell adhesion and its dynamics. The setup allowed measurements of adhesion forces up to the μN range, and total detachment distances over 40 μm. Force-distance curves have been fitted with a simple elastic model including a cell detachment protocol in order to estimate the Young's modulus of the cells, as well as to reveal changes in the dynamic properties as functions of the applied current dose. While the cell spreading area decreased monotonously with increasing current doses, small current doses resulted only in differences related to cell elasticity. Current doses above 11 As/m(2), however, initiated more drastic changes in cell morphology, viability, cellular structure, as well as in properties related to cell adhesion. The observed differences, eventually leading to cell death toward higher doses, might originate from both the decrease in pH and the generation of reactive oxygen species.

  16. Particle-in-cell simulations of the high current experiment

    International Nuclear Information System (INIS)

    The particle-in-cell code WARP has been used to simulate beam dynamics for the intense ion beam of the High Current Experiment. First a study was done of the dynamic aperture of the alternating-gradient electrostatic quadrupole lattice of the experiment, including nonlinearity due to image forces and imperfections of the focusing lattice field. It was found that particle loss, rather than emittance growth, determined the usable aperture. Simulations of transport in the High Current Experiment were then performed, and the results compared to measured data. We present the results of both of these studies

  17. [Current cell therapy strategies for repairing the central nervous system].

    Science.gov (United States)

    Féron, F

    2007-09-01

    One of the chief contemporary goals of neurologists and neuroscientists is to find a way to overcome the debilitating effects of brain diseases, especially neurodegenerative diseases. Since very few molecules have been found to be efficient in curing the patients and even halting the progression of the symptoms, cell therapy is now seen as an attractive alternative. Two therapeutic strategies are currently under investigation: i) the "substitution" strategy, based on grafts of cells capable of differentiating in the appropriate cells and restoring lost functions and ii) the "neuroprotective" or "conservative" strategy aiming to increase the resistance of spared cells to the toxicity of their environment and to reinforce the body's own mechanisms of healing. Twenty years ago, foetal neuroblasts were the first cells to be transplanted in the brains of patients with Parkinson's or Huntington disease. A phase II clinical trial is presently conducted in France for the latter disorder. However, the numerous ethical and technical issues raised by the use of embryonic and foetal cells have directed the focus of clinicians and researchers towards substitute cell types. In this review, we summarise the main findings of the most recent basic studies and clinical trials based on: i) the grafting of surrogate adult cells such as bone marrow mesenchymal stem cells and olfactory ensheathing cells; ii) the potential therapeutic applications of neuropoiesis - the persistent neurogenesis in the brain - as a source for tissue engraftment and as self-repair by a person's own indigenous population of pluripotent cells and iii) immune-based therapy (autologous activated macrophages and T cell vaccination) as well as administration of immunomodulatory molecules. Unexpectedly, it has been found that undifferentiated adult stem cells can display immune-like functions when they home in on an inflamed brain area while immune cells and immunosuppressors can improve functional and

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

    OpenAIRE

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

    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 distribu...

  19. 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.

  20. Fibrocytes and the tissue niche in lung repair.

    Science.gov (United States)

    Andersson-Sjöland, Annika; Nihlberg, Kristian; Eriksson, Leif; Bjermer, Leif; Westergren-Thorsson, Gunilla

    2011-01-01

    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. PMID:21658209

  1. 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.

  2. Cell carriers for oncolytic viruses: current challenges and future directions

    Directory of Open Access Journals (Sweden)

    Roy DG

    2013-10-01

    Full Text Available Dominic G Roy,1,2 John C Bell1–31Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, 2Department of Biochemistry, Immunology and Microbiology, 3Department of Medicine, University of Ottawa, Ottawa, ON, CanadaAbstract: The optimal route for clinical delivery of oncolytic viruses is thought to be systemic intravenous injection; however, the immune system is armed with several highly efficient mechanisms to remove pathogens from the circulatory system. To overcome the challenges faced in trying to delivery oncolytic viruses specifically to tumors via the bloodstream, carrier cells have been investigated to determine their suitability as delivery vehicles for systemic administration of oncolytic viruses. Cell carriers protect viruses from neutralization, one of the most limiting aspects of oncolytic virus interaction with the immune system. Cell carriers can also possess inherent tumor tropism, thus directing the delivery of the virus more specifically to a tumor. With preclinical studies already demonstrating the success and feasibility of this approach with multiple oncolytic viruses, clinical evaluation of cell-mediated delivery of viruses is on the horizon. Meanwhile, ongoing preclinical studies are aimed at identifying new cellular vehicles for oncolytic viruses and improving current promising cell carrier platforms.Keywords: oncolytic virus, cell carrier, systemic delivery, tumor targeting, cancer

  3. 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.

  4. 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.

  5. 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.

  6. Ecological niche of plant pathogens

    Directory of Open Access Journals (Sweden)

    Ecaterina Fodor

    2011-06-01

    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 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. 

  7. 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.

  8. 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.

  9. 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

  10. Current and Future Stem Cell Regulation: A Call to Action.

    Science.gov (United States)

    Anz, Adam

    2016-01-01

    The orthopedic sports medicine profession experienced a pivotal shift with the acceptance and application of the arthroscope. The next leap forward will hinge on the acceptance, application, and regulation of biologic therapies, and a sentinel event will be the US Food and Drug Administration approval of a stem cell technology. While the arthroscope was developed in the hands of our sports medicine mentors, the current history of biologics has been mostly written by basic scientists. The baby steps of these technologies have involved benchtop laboratory studies and preclinical animal trials, clearly illustrating great potential. Clinical progress has struggled forward but stalled. Regulatory constraints and our inability to establish safety and efficacy are the major hurdles, with disconnect between the basic scientist, clinician, and regulatory bodies to blame. While the development of the arthroscope was barely influenced by governmental regulation, this will control and model the future of stem cell technologies. With current legislation before Congress concerning stem cell regulation, the next steps are dependent upon the clinician's understanding and participation in this regulation. PMID:27552450

  11. 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.

  12. Synthetic niche to modulate regenerative potential of MSCs and enhance skeletal muscle regeneration.

    Science.gov (United States)

    Pumberger, Matthias; Qazi, Taimoor H; Ehrentraut, M Christine; Textor, Martin; Kueper, Janina; Stoltenburg-Didinger, Gisela; Winkler, Tobias; von Roth, Philipp; Reinke, Simon; Borselli, Cristina; Perka, Carsten; Mooney, David J; Duda, Georg N; Geißler, Sven

    2016-08-01

    Severe injury to the skeletal muscle often results in the formation of scar tissue, leading to a decline in functional performance. Traditionally, tissue engineering strategies for muscle repair have focused on substrates that promote myogenic differentiation of transplanted cells. In the current study, the reported data indicates that mesenchymal stromal cells (MSCs) transplanted via porous alginate cryogels promote muscle regeneration by secreting bioactive factors that profoundly influence the function of muscle progenitor cells. These cellular functions, which include heightened resistance of muscle progenitor cells to apoptosis, migration to site of injury, and prevention of premature differentiation are highly desirable in the healing cascade after acute muscle trauma. Furthermore, stimulation of MSCs with recombinant growth factors IGF-1 and VEGF165 was found to significantly enhance their paracrine effects on muscle progenitor cells. Multifunctional alginate cryogels were then utilized as synthetic niches that facilitate local stimulation of seeded MSCs by providing a sustained release of growth factors. In a clinically relevant injury model, the modulation of MSC paracrine signaling via engineered niches significantly improved muscle function by remodeling scar tissue and promoting the formation of new myofibers, outperforming standalone cell or growth factor delivery. PMID:27235995

  13. Calcium release-activated calcium current in rat mast cells.

    Science.gov (United States)

    Hoth, M; Penner, R

    1993-06-01

    1. Whole-cell patch clamp recordings of membrane currents and fura-2 measurements of free intracellular calcium concentration ([Ca2+]i) were used to study the biophysical properties of a calcium current activated by depletion of intracellular calcium stores in rat peritoneal mast cells. 2. Calcium influx through an inward calcium release-activated calcium current (ICRAC) was induced by three independent mechanisms that result in store depletion: intracellular infusion of inositol 1,4,5-trisphosphate (InsP3) or extracellular application of ionomycin (active depletion), and intracellular infusion of calcium chelators (ethylene glycol bis-N,N,N',N'-tetraacetic acid (EGTA) or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)) to prevent reuptake of leaked-out calcium into the stores (passive depletion). 3. The activation of ICRAC induced by active store depletion has a short delay (4-14 s) following intracellular infusion of InsP3 or extracellular application of ionomycin. It has a monoexponential time course with a time constant of 20-30 s and, depending on the complementary Ca2+ buffer, a mean normalized amplitude (at 0 mV) of 0.6 pA pF-1 (with EGTA) and 1.1 pA pF-1 (with BAPTA). 4. After full activation of ICRAC by InsP3 in the presence of EGTA (10 mM), hyperpolarizing pulses to -100 mV induced an instantaneous inward current that decayed by 64% within 50 ms. This inactivation is probably mediated by [Ca2+]i, since the decrease of inward current in the presence of the fast Ca2+ buffer BAPTA (10 mM) was only 30%. 5. The amplitude of ICRAC was dependent on the extracellular Ca2+ concentration with an apparent dissociation constant (KD) of 3.3 mM. Inward currents were nonsaturating up to -200 mV. 6. The selectivity of ICRAC for Ca2+ was assessed by using fura-2 as the dominant intracellular buffer (at a concentration of 2 mM) and relating the absolute changes in the calcium-sensitive fluorescence (390 nm excitation) with the calcium current integral

  14. A NICHE FOR ISOTOPIC ECOLOGY

    Science.gov (United States)

    Fifty years ago, GE Hutchinson defined the ecological niche as a hypervolume in n-dimensional space with environmental variables as axes. Ecologists have recently developed renewed interest in the concept, and technological advances now allow us to use stable isotope analyses to ...

  15. 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

  16. The niche construction perspective: a critical appraisal

    OpenAIRE

    Scott-Phillips, Thomas C.; Laland, Kevin N.; Shuker, David M.; Dickins, Thomas E.; West, Stuart A.

    2014-01-01

    Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equival...

  17. The niche construction perspective: a critical appraisal.

    OpenAIRE

    Scott-Phillips, Thomas C.; Laland, Kevin N.; Shuker, David M.; Dickins, Thomas E.; West, Stuart A.

    2014-01-01

    Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equival...

  18. 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.

  19. 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.

  20. Ontogenetic niche shifts in three Vaccinium species on a sub-alpine mountain side

    DEFF Research Database (Denmark)

    Auffret, Alistair G.; Meineri, Eric; Bruun, Hans Henrik;

    2010-01-01

    Background: Climate warming in arctic and alpine regions is expected to result in the altitudinal migration of plant species, but current predictions neglect differences between species' regeneration niche and established niche. Aims: To examine potential recruitment of Vaccinium myrtillus, V...... recruitment in habitats at altitudes above its current populations. Conclusions: The potential for migration exists, but incongruence between regenerative and established niches presents a challenge for colonisers, as well as for plant migration modelling...

  1. Discovery of fungus-mite mutualism in a unique niche

    NARCIS (Netherlands)

    Roets, F; Wingfield, M J; Crous, P W; Dreyer, L L

    2007-01-01

    The floral heads (infructescences) of South African Protea L. represent a most unusual niche for fungi of the economically important genus Ophiostoma Syd. and P. Syd. emend. Z.W. de Beer et al. Current consensus holds that most members of Ophiostoma are vectored by tree-infesting bark beetles. Howev

  2. 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...

  3. High-Ts amorphous top cells for increased top cell currents in micromorph tandem cells

    OpenAIRE

    Platz, R.; Hof, Ch.; Fischer, Diego; Meier, Johannes; Shah, Arvind

    2008-01-01

    In the present paper, the authors discuss the application of amorphous p–i–n solar cells containing i-layers which are deposited at high substrate temperatures as top cells in amorphous silicon/microcrystalline silicon tandem (“micromorph”) solar cells. Increasing the substrate temperature for the deposition of intrinsic a-Si : H results in a reduced optical gap. The optical absorption is enhanced and thereby the current generation. A high-current generation within a relatively thin amorphous...

  4. Niche energy markets in rural areas

    International Nuclear Information System (INIS)

    The objective of this project is the development of a standard methodology for integrating non-food crops in rural areas with niche energy markets. This has involved a number of steps including (i) identification of 3 niche markets for energy crops which are of common interest to the partners, (ii) application of the standard costing methodology to investigate these three niche markets and (iii) comparison of the results from this work in three workshops (one for each market). Three tightly defined niche markets were identified; these were chosen following an examination of the national energy marekts in each of the partners countries (Ireland, Germany, Netherlands, UK, Greece and Portugal). This paper gives an overview of the national energy markets which were examined. The three niche markets are introduced and the reasons for their selection given. The application of the methodology to each of the niche markets is presented along with the conclusions of the partners regarding the niche markets. (Author)

  5. Evolution of climate niches in European mammals?

    Science.gov (United States)

    Dormann, Carsten F; Gruber, Bernd; Winter, Marten; Herrmann, Dirk

    2010-04-23

    Our ability to predict consequences of climate change is severely impaired by the lack of knowledge on the ability of species to adapt to changing environmental conditions. We used distribution data for 140 mammal species in Europe, together with data on climate, land cover and topography, to derive a statistical description of their realized climate niche. We then compared climate niche overlap of pairs of species, selected on the basis of phylogenetic information. In contrast to expectations, related species were not similar in their climate niche. Rather, even species pairs that had a common ancestor less than 1 Ma already display very high climate niche distances. We interpret our finding as a strong interspecific competitive constraint on the realized niche, rather than a rapid evolution of the fundamental niche. If correct, our results imply a very limited usefulness of climate niche models for the prediction of future mammal distributions. PMID:19828492

  6. 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.

  7. High-T{sub s} amorphous top cells for increased top cell currents in micromorph tandem cells

    Energy Technology Data Exchange (ETDEWEB)

    Platz, Rainer; Hof, C.; Fischer, D.; Meier, J.; Shah, A. [Institut de Microtechnique, Universite de Neuchatel, Neuchatel (Switzerland)

    1998-05-12

    In the present paper, the authors discuss the application of amorphous p-i-n solar cells containing i-layers which are deposited at high substrate temperatures as top cells in amorphous silicon/microcrystalline silicon tandem (`micromorph`) solar cells. Increasing the substrate temperature for the deposition of intrinsic a-Si:H results in a reduced optical gap. The optical absorption is enhanced and thereby the current generation. A high-current generation within a relatively thin amorphous top cell is very interesting in the context of micromorph tandem cells, where the amorphous top cell should contribute a current of at least 13 mA/cm{sup 2} for a total cell current density of 26 mA/cm{sup 2}. A detailed study of the intrinsic material deposited by VHF-GD at 70 MHz at substrate temperatures between 220C and 360C is presented, including samples deposited from hydrogen-diluted silane plasmas. The stability of the films against light soaking is investigated employing the {mu}{sub 0}{tau}{sub 0} parameter, which has been shown to be directly correlated to the cell performance. The paper discusses in detail the technological problems arising from the insertion of i-layers deposited at high substrate temperatures into solar cells. These problems are specially pronounced in the case of cells in the p-i-n (superstrate) structure. The authors demonstrate that an appropriate interface layer at the p/i-interface can largely reduce the detrimental effects of i-layer deposition at high temperatures. Finally, the application of such optimized high-temperature amorphous cells as top cells in micromorph tandem cells is discussed. Current densities of 13 mA/cm{sup 2} in the top cell are available with a top cell i-layer thickness of only 250 nm

  8. 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.

  9. Niche market analysis: healthy nutrition

    OpenAIRE

    Chlivényiová, Eva

    2012-01-01

    The purpose of this Master's Thesis is to consider preferences of the consumers on the market of healthy nutrition and trends on this market. The Thesis analyzes if the niche on the market of healthy nutrition really exists and tries to predict future development of the healthy nutrition through the found out facts. The topic of this Master's Thesis was chosen because healthy lifestyle represents a hot topic for many discussions. This Thesis includes theoretical and analytical parts. Importan...

  10. Desmoplastic Small Round Cell Tumor: Current Management and Recent Findings

    Directory of Open Access Journals (Sweden)

    Armelle Dufresne

    2012-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive mesenchymal tumor that develops in the abdominal cavity of young men adults. Patients typically present with symptoms of abdominal sarcomatosis. Diagnosis is based on histological analysis of biopsies which typically show small round blue cells in nests separated by an abundant desmoplastic stroma. DSRCT is associated with a unique chromosomal translocation t(11:22 (p 13; q 12 that involves the EWSR1 and WT1 genes. The prognosis is particularly poor; median survival ranges from 17 to 25 months, largely due to the presentation of the majority of patients with metastatic disease. Management of DSRCT remains challenging and current schemes lack a significant cure rate despite the use of aggressive treatments such as polychemotherapy, debulking surgery and whole abdominal radiation. Several methods are being evaluated to improve survival: addition of chemotherapy and targeted therapies to standard neoadjuvant protocol, completion of surgical resection with HIPEC, postoperative IMRT, treatment of hepatic metastases with [90Y]Yttrium microsphere liver embolization.

  11. Niche-specific cognitive strategies

    DEFF Research Database (Denmark)

    Hulgard, K.; Ratcliffe, J. M.

    2014-01-01

    Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should ...... the niche-specific cognitive strategies hypothesis and suggest that for gleaning and clutter-resistant aerial hawking bats, learning to associate shape with food interferes with subsequent spatial memory learning.......Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should...... rely more on object memory than on spatial memory for finding food and that the opposite is true of frugivorous and nectivorous species. Specifically, we predicted that: (1) predatory bats would readily learn to associate shapes with palatable prey and (2) once bats had made such associations...

  12. 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.

  13. Evolution of niche width and adaptive diversification.

    Science.gov (United States)

    Ackermann, Martin; Doebeli, Michael

    2004-12-01

    Theoretical models suggest that resource competition can lead to the adaptive splitting of consumer populations into diverging lineages, that is, to adaptive diversification. In general, diversification is likely if consumers use only a narrow range of resources and thus have a small niche width. Here we use analytical and numerical methods to study the consequences for diversification if the niche width itself evolves. We found that the evolutionary outcome depends on the inherent costs or benefits of widening the niche. If widening the niche did not have costs in terms of overall resource uptake, then the consumer evolved a niche that was wide enough for disruptive selection on the niche position to vanish; adaptive diversification was no longer observed. However, if widening the niche was costly, then the niche widths remained relatively narrow, allowing for adaptive diversification in niche position. Adaptive diversification and speciation resulting from competition for a broadly distributed resource is thus likely if the niche width is fixed and relatively narrow or free to evolve but subject to costs. These results refine the conditions for adaptive diversification due to competition and formulate them in a way that might be more amenable for experimental investigations. PMID:15696740

  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. Current overview on dental stem cells applications in regenerative dentistry

    OpenAIRE

    Bansal, Ramta; Jain, Aditya

    2015-01-01

    Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental...

  16. Optimal management of metastatic renal cell carcinoma: current status.

    Science.gov (United States)

    Escudier, Bernard; Albiges, Laurence; Sonpavde, Guru

    2013-04-01

    this setting. Optimal sequencing of agents and individualized therapy based on biomarkers is undergoing investigation. Today, the choice of therapy is based on patient and physician decision, which is a function of comorbidities, toxicity profiles and costs. Clinical trials evaluating novel agents and combinations should be preferred when available since agents in the current therapeutic arsenal have not yielded cures despite extending median survival to greater than 2 years. One noteworthy new class of agents that has yielded durable responses is programmed death (PD)-1 inhibitors, which target a T-lymphocyte checkpoint and are heralding a resurgence of immunotherapy. Finally, optimal therapy for non-clear cell RCC remains to be delineated, although sunitinib, everolimus and other VEGFR-TKI or mTOR inhibitors have all demonstrated modest benefit. PMID:23572408

  17. 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.

  18. 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

  19. 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.

  20. Human niche construction in interdisciplinary focus

    OpenAIRE

    Kendal, Jeremy; Tehrani, Jamshid J.; Odling-Smee, John

    2011-01-01

    Niche construction is an endogenous causal process in evolution, reciprocal to the causal process of natural selection. It works by adding ecological inheritance, comprising the inheritance of natural selection pressures previously modified by niche construction, to genetic inheritance in evolution. Human niche construction modifies selection pressures in environments in ways that affect both human evolution, and the evolution of other species. Human ecological inheritance is exceptionally po...

  1. Exploring dynamics and strategies of niche protection

    OpenAIRE

    Boon, W.P.C.; Moors, Ellen H M; Meijer, Albert J.

    2014-01-01

    This paper focuses on the processes and strategies of advocates and opponents in creating, maintaining and/or contesting the protective spaces in which 'urgently needed' but 'risky' pharmaceutical innovations are managed. Drawing on transition literature and recent work on niche protection, this paper adds to the conceptualisation and empirical grounding of niche protection by studying the dynamics of protection, in particular the different phases of niche development. Moreover, the links bet...

  2. 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.

  3. Modelling the regenerative niche: a major challenge in biomaterials research.

    Science.gov (United States)

    Kirkpatrick, C James

    2015-12-01

    By definition, biomaterials are developed for clinical application. In the field of regenerative medicine their principal function is to play a significant, and, if possible, an instructive role in tissue healing. In the last analysis the latter involves targeting the 'regenerative niche'. The present paper will address the problem of simulating this niche in the laboratory and adopts a life science approach involving the harnessing of heterotypic cellular communication to achieve this, that is, the ability of cells of different types to mutually influence cellular functions. Thus, co-culture systems using human cells are the methodological focus and will concern four exemplary fields of regeneration, namely, bone, soft tissue, lower respiratory tract and airway regeneration. The working hypothesis underlying this approach is that in vitro models of higher complexity will be more clinically relevant than simple monolayer cultures of transformed cell lines in testing innovative strategies with biomaterials for regeneration. PMID:26816650

  4. 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. PMID:27053524

  5. 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

  6. Cytoarchitecture and Ultrastructure of Neural Stem Cell Niches and Neurogenic Complexes Maintaining Adult Neurogenesis in the Olfactory Midbrain of Spiny Lobsters, Panulirus argus

    OpenAIRE

    Schmidt, Manfred; Derby, Charles D.

    2011-01-01

    New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labelin...

  7. 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.

  8. Fractal heterogeneity in minimal matrix models of scars modulates stiff-niche stem-cell responses via nuclear exit of a mechanorepressor

    Science.gov (United States)

    Dingal, P. C. Dave P.; Bradshaw, Andrew M.; Cho, Sangkyun; Raab, Matthew; Buxboim, Amnon; Swift, Joe; Discher, Dennis E.

    2015-09-01

    Scarring is a long-lasting problem in higher animals, and reductionist approaches could aid in developing treatments. Here, we show that copolymerization of collagen I with polyacrylamide produces minimal matrix models of scars (MMMS), in which fractal-fibre bundles segregate heterogeneously to the hydrogel subsurface. Matrix stiffens locally--as in scars--while allowing separate control over adhesive-ligand density. The MMMS elicits scar-like phenotypes from mesenchymal stem cells (MSCs): cells spread and polarize quickly, increasing nucleoskeletal lamin-A yet expressing the `scar marker' smooth muscle actin (SMA) more slowly. Surprisingly, expression responses to MMMS exhibit less cell-to-cell noise than homogeneously stiff gels. Such differences from bulk-average responses arise because a strong SMA repressor, NKX2.5, slowly exits the nucleus on rigid matrices. NKX2.5 overexpression overrides rigid phenotypes, inhibiting SMA and cell spreading, whereas cytoplasm-localized NKX2.5 mutants degrade in well-spread cells. MSCs thus form a `mechanical memory' of rigidity by progressively suppressing NKX2.5, thereby elevating SMA in a scar-like state.

  9. Stitch the niche - a practical philosophy and visual schematic for the niche concept

    NARCIS (Netherlands)

    McInerny, Greg J.; Etienne, Rampal S.

    2012-01-01

    By over-focusing on precise definitions, ecology has produced a confused idea of the niche concept. This, our second paper, develops a practical philosophy for the niche that approaches the concept at the correct level of abstraction. We deconstruct the niche into effect and response components and

  10. Ditch the niche - is the niche a useful concept in ecology or species distribution modelling?

    NARCIS (Netherlands)

    McInerny, Greg J.; Etienne, Rampal S.

    2012-01-01

    In this first of three papers we examine the use of niche concepts in ecology and especially in species distribution modelling (SDM). This paper deliberately focuses on the lack of clarity found in the term niche. Because its meanings are so diverse, the term niche tends to create confusion and requ

  11. 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.

  12. 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.

  13. 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.

  14. An Adaptive Niching Genetic Algorithm using a niche size equalization mechanism

    Science.gov (United States)

    Nagata, Yuichi

    Niching GAs have been widely investigated to apply genetic algorithms (GAs) to multimodal function optimization problems. In this paper, we suggest a new niching GA that attempts to form niches, each consisting of an equal number of individuals. The proposed GA can be applied also to combinatorial optimization problems by defining a distance metric in the search space. We apply the proposed GA to the job-shop scheduling problem (JSP) and demonstrate that the proposed niching method enhances the ability to maintain niches and improve the performance of GAs.

  15. 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

  16. EUBrazilOpenBio - Niche modelling services

    OpenAIRE

    Rebello, Vinod; De Giovanni, Renato; Candela, Leonardo

    2012-01-01

    This report concerns Ecological Niche Modelling - also known as environmental niche modelling - as used in the EUBrazilOpenBio Project to provide, through the aggregation of various computational and data technologies, a coherent and integrated research environment to be used by scientists and external applications, particularly from the area of biodiversity.

  17. Niche models tell half the story

    DEFF Research Database (Denmark)

    Swab, Rebecca Marie; Regan, Helen M.; Keith, David A.;

    2012-01-01

    Aim  While niche models are typically used to assess the vulnerability of species to climate change, they have been criticized for their limited assessment of threats other than climate change. We attempt to evaluate this limitation by combining niche models with life-history models to investigat...

  18. 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…

  19. LEG ULCERS IN SICKLE CELL DISEASE: CURRENT PATTERNS AND PRACTICES

    OpenAIRE

    Delaney, Kara-Marie H.; Axelrod, Karen C.; Buscetta, Ashley; Hassell, Kathryn L.; Adams-Graves, Patricia E.; Seamon, Catherine; Kato, Gregory J.; Minniti, Caterina P.

    2013-01-01

    Leg ulcers are a debilitating complication of patients with sickle cell disease, and their frequency in North America was reported to be 2.5% by the Cooperative Study of Sickle Cell Disease more than 20 years ago. We sought to determine if the frequency of leg ulcers in sickle cell patients in the United States had declined and to assess which treatments providers use most commonly. We sent an e-mail survey to health professionals belonging to the national Sickle Cell Adult Provider Network. ...

  20. MOS current gain cells with electronically variable gain and constant bandwidth

    NARCIS (Netherlands)

    Klumperink, Eric A.M.; Seevinck, Evert

    1989-01-01

    Two MOS current gain cells are proposed that provide linear amplification of currents supplied by several linear MOS V-I converters. The gain is electronically variable by a voltage or a current and can be made insensitive to temperature and IC processing. The gain cells have a constant (gain-indepe

  1. MOS current gain cells with electronically variable gain and constant bandwidth

    OpenAIRE

    Klumperink, Eric A.M.; Seevinck, Evert

    1989-01-01

    Two MOS current gain cells are proposed that provide linear amplification of currents supplied by several linear MOS V-I converters. The gain is electronically variable by a voltage or a current and can be made insensitive to temperature and IC processing. The gain cells have a constant (gain-independent) bandwidth

  2. Ecological Niche Modeling of Cryptococcus gattii in British Columbia, Canada

    OpenAIRE

    Mak, Sunny; Klinkenberg, Brian; Bartlett, Karen; Fyfe, Murray

    2009-01-01

    Background Cryptococcus gattii emerged on Vancouver Island, British Columbia (BC), Canada, in 1999, causing human and animal illness. Environmental sampling for C. gattii in southwestern BC has isolated the fungal organism from native vegetation, soil, air, and water. Objectives Our aim was to help public health officials in BC delineate where C. gattii is currently established and forecast areas that could support C. gattii in the future. We also examined the utility of ecological niche mode...

  3. 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.

  4. 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.

  5. 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.

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

    OpenAIRE

    Leskošek-Čukalov Ida J.; Nedović Viktor A.

    2005-01-01

    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 sit...

  7. 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.

  8. Current status of demonstration for stationary fuel cell in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Park, D.R. [Korea Gas Co., Ansan (Korea, Republic of). Research and Development Div.

    2009-07-01

    In 2006, the Korean Government launched the Residential Fuel Cell Monitoring Project to address the barriers to the widespread commercialization of fuel cells for residential power generation (RPG). This presentation reviewed the status on the development and dissemination of the residential fuel cell in Korea, with particular reference to a domestically developed proton exchange membrane (PEM) fuel cell for RPG. The purpose of the project was to find a commercial product that is suitable to Korean life style and to solve reliability issues regarding grid connection. The paper showed that although residential fuel cell systems are available in Korea, their capital cost remains high and system durability is not sufficient. This large-scale demonstration test project for residential fuel cell systems was launched in an effort to reduce the cost to levels that are acceptable for wide scale use. A total of 210 unit were tested in order to evaluate the technical level and to investigate the problems that must be solved for mass market introduction.

  9. 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...... collectors were studied: Au, Ni, Ag, and Pt. It was shown that the performance of the direct carbon fuel cell (DCFC) is dependent on the current collector materials, Ni and Pt giving the best performance, due to their catalytic activity. Gold is suggested to be the best material as an inert current collector...

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. The United States pork niche market phenomenon.

    Science.gov (United States)

    Honeyman, M S; Pirog, R S; Huber, G H; Lammers, P J; Hermann, J R

    2006-08-01

    After the broad industrialization of the US pork industry, there has been a development of niche markets for export and domestic pork; that is, there is a pork niche market phenomenon. The US pork niche market phenomenon is characterized, and 2 of the major markets are explained in detail. With the Midwest's tradition of a diversified family-based agriculture and record low hog prices of the late 1990s, the conditions were conducive for this phenomenon to develop. Pork niche markets utilize various sales methods including Internet sales, local abattoir sales, direct marketing, farmer networks, and targeting to organized groups. In 2003, there were approximately 35 to 40 active pork niche marketing efforts in Iowa. The Berkshire breed is an example of a swine breed that has had a recent resurgence because of niche markets. Berkshire pork is known for tenderness and excellent quality. Berkshire registrations have increased 4-fold in the last 10 yr. One of the larger niche marketers of "natural pork" is Niman Ranch Pork, which has more than 400 farmer-producers and processes about 2,500 pigs weekly. Many US consumers of pork are interested in issues concerning the environment, food safety, pig welfare, and pig farm ownership and structure. These consumers may be willing to pay more for pork from farmers who are also concerned about these issues. Small- and medium-sized swine farmers are active in pork niche markets. Niche markets claim product differentiation by superior or unique product quality and social attributes. Quality attributes include certain swine breeds, and meat quality, freshness, taste or flavor, and tenderness. Social or credence attributes often are claimed and include freedom from antibiotics and growth promotants; local family farm production; natural, organic, outdoor, or bedded rearing; humane rearing; known origin; environmentally friendly production; and the absence of animal by-products in the feed. Niche pork markets and alternative swine

  16. 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...

  17. 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...

  18. 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)

  19. 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.

  20. 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.

  1. 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.

  2. Current status of haploidentical stem cell transplantation for leukemia

    Directory of Open Access Journals (Sweden)

    Huang Xiao-jun

    2008-12-01

    Full Text Available Abstract Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD, graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy.

  3. CD133 identifies perivascular niches in grade II-IV astrocytomas

    DEFF Research Database (Denmark)

    Christensen, Karina; Schrøder, Henrik; Kristensen, Bjarne

    2008-01-01

    expression of CD133 in paraffin sections was analysed using morphometry. In all grades, CD133 was expressed on tumour and endothelial cells. Tumour cells were found in perivascular niches, as dispersed single cells and in pseudopalisade formations around necrosis. There was no correlation between the mean...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. Improved carrier extraction of solar cell using transparent current spreading layer

    International Nuclear Information System (INIS)

    An as-deposited ultra thin metal film was fine-etched to a mesh with average optical transmittance of 70.83%. When this metal mesh was applied to the fabrication of solar cell, it was transparent and conductive to be used as a current-spreading layer. Such a current-spreading layer was good for the carrier extraction of illuminated solar cell. Then the non-uniform two-dimensional current flow on the resistive central emitter region of solar cell can be reduced efficiently by this metal mesh. The metal mesh integrated solar cell can result in improvements of 26.15% for short-circuit current and 30% for the conversion efficiency, respectively. - Highlights: • An as-deposited thin metal thin film is fine-etched to a transparent mesh. • A transparent metal mesh acts as a current-spreading layer for solar cells. • A transparent metal mesh allows photons going through and carriers conducting

  10. 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.

  11. Assessing niche width of endothermic fish from genes to ecosystem.

    Science.gov (United States)

    Madigan, Daniel J; Carlisle, Aaron B; Gardner, Luke D; Jayasundara, Nishad; Micheli, Fiorenza; Schaefer, Kurt M; Fuller, Daniel W; Block, Barbara A

    2015-07-01

    Endothermy in vertebrates has been postulated to confer physiological and ecological advantages. In endothermic fish, niche expansion into cooler waters is correlated with specific physiological traits and is hypothesized to lead to greater foraging success and increased fitness. Using the seasonal co-occurrence of three tuna species in the eastern Pacific Ocean as a model system, we used cardiac gene expression data (as a proxy for thermal tolerance to low temperatures), archival tag data, and diet analyses to examine the vertical niche expansion hypothesis for endothermy in situ. Yellowfin, albacore, and Pacific bluefin tuna (PBFT) in the California Current system used more surface, mesopelagic, and deep waters, respectively. Expression of cardiac genes for calcium cycling increased in PBFT and coincided with broader vertical and thermal niche utilization. However, the PBFT diet was less diverse and focused on energy-rich forage fishes but did not show the greatest energy gains. Ecosystem-based management strategies for tunas should thus consider species-specific differences in physiology and foraging specialization. PMID:26100889

  12. Biodiversity influences plant productivity through niche-efficiency.

    Science.gov (United States)

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

    2015-05-01

    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.

  13. 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.)

  14. 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

  15. 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......+ 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......-dependent changes in the capacity for conductive Cl- transport. It is suggested that in ELA cells, entrance into the S phase requires an increase in VRAC activity and/or an increased potential for regulatory volume decrease (RVD), and at the same time a decrease in CaCC magnitude....

  16. Opto-electronic analysis of silicon solar cells by LBIC investigations and current-voltage characterization

    Energy Technology Data Exchange (ETDEWEB)

    Thantsha, N.M.; Macabebe, E.Q.B.; Vorster, F.J. [Department of Physics, PO Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Dyk, E.E. van, E-mail: ernest.vandyk@nmmu.ac.z [Department of Physics, PO Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa)

    2009-12-01

    A different laser beam induced current (LBIC) mapping technique has been used for the measurements of spatial variation of light generated current of a solar cell. These variations are caused by parasitic resistances and defects at grain boundaries (GBs) in multicrystalline silicon solar cells (mc-Si). This study investigates and identifies the regions within mc-Si solar cells where dominating recombination and lifetime limiting processes occur. A description of the LBIC technique is presented and the results show how multicrystalline GBs and other defects affect the light generated current of a spot illuminated mc-Si solar cell. The results of the internal quantum efficiency (IQE) at wavelength of 660 nm revealed that some regions in mc-Si solar cell give rise to paths that lead current away from the intended load.

  17. Opto-electronic analysis of silicon solar cells by LBIC investigations and current-voltage characterization

    International Nuclear Information System (INIS)

    A different laser beam induced current (LBIC) mapping technique has been used for the measurements of spatial variation of light generated current of a solar cell. These variations are caused by parasitic resistances and defects at grain boundaries (GBs) in multicrystalline silicon solar cells (mc-Si). This study investigates and identifies the regions within mc-Si solar cells where dominating recombination and lifetime limiting processes occur. A description of the LBIC technique is presented and the results show how multicrystalline GBs and other defects affect the light generated current of a spot illuminated mc-Si solar cell. The results of the internal quantum efficiency (IQE) at wavelength of 660 nm revealed that some regions in mc-Si solar cell give rise to paths that lead current away from the intended load.

  18. Exploring dark current voltage characteristics of micromorph silicon tandem cells with computer simulations

    OpenAIRE

    Sturiale, A.; Li, H. B. T.; Rath, J.K.; R. E. I. Schropp; Rubinelli, F.A.

    2009-01-01

    The transport mechanisms controlling the forward dark current-voltage characteristic of the silicon micromorph tandem solar cell were investigated with numerical modeling techniques. The dark current-voltage characteristics of the micromorph tandem structure at forward voltages show three regions: two with an exponential dependence and a third where the current grows more slowly with the applied voltage. In the first exponential region the current is entirely controlled by recombination throu...

  19. Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.

    Science.gov (United States)

    Roh, Kyung-Ho; Nerem, Robert M; Roy, Krishnendu

    2016-06-01

    Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules. This paradigm shift in modern medicine of using cells as novel therapeutics can be realized only if suitable manufacturing technologies for large-scale, cost-effective, reproducible production of high-quality cells can be developed. Here we review the state of the art in therapeutic cell manufacturing, including cell purification and isolation, activation and differentiation, genetic modification, expansion, packaging, and preservation. We identify current challenges and discuss opportunities to overcome them such that cell therapies become highly effective, safe, and predictively reproducible while at the same time becoming affordable and widely available. PMID:27276552

  20. 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.

  1. 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].

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. 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. PMID:20718315

  7. 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.

  8. Diabetes treatment: A rapid review of the current and future scope of stem cell research.

    Science.gov (United States)

    Sheik Abdulazeez, Sheriff

    2015-09-01

    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 the world and are successful in producing insulin secreting cells. The different type of stem cells (induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs) and adult stem cells) proves to be potent in treating diabetes with certain limitations. This article precisely reviews the resources and progress made in the field of stem cell research for diabetic treatment.

  9. 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.

  10. 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.

  11. Exploring dark current voltage characteristics of micromorph silicon tandem cells with computer simulations

    Science.gov (United States)

    Sturiale, A.; Li, Hongbo T.; Rath, J. K.; Schropp, R. E. I.; Rubinelli, F. A.

    2009-07-01

    The transport mechanisms controlling the forward dark current-voltage characteristic of the silicon micromorph tandem solar cell were investigated with numerical modeling techniques. The dark current-voltage characteristics of the micromorph tandem structure at forward voltages show three regions: two with an exponential dependence and a third where the current grows more slowly with the applied voltage. In the first exponential region the current is entirely controlled by recombination through gap states of the top cell. In the second exponential region the current is controlled by the mixture of recombination through gap states of both the top and bottom cells and by free carrier diffusion along the a-Si:H intrinsic layer. In the third region the onset of the electron space charge limited current on the a-Si:H top cell can be observed along with some other mechanisms that are discussed in the paper. The high forward dark J-V curve of the tandem cell can be used as diagnosis tool to quickly inspect the efficiency of the recombination junction in recombining the electron-hole pairs generated under illumination in the top and bottom cells. The dark current at high forward voltages is highly influenced by the amount of electron-hole pairs thermally generated inside the recombination junction.

  12. Current density distribution in cylindrical Li-Ion cells during impedance measurements

    Science.gov (United States)

    Osswald, P. J.; Erhard, S. V.; Noel, A.; Keil, P.; Kindermann, F. M.; Hoster, H.; Jossen, A.

    2016-05-01

    In this work, modified commercial cylindrical lithium-ion cells with multiple separate current tabs are used to analyze the influence of tab pattern, frequency and temperature on electrochemical impedance spectroscopy. In a first step, the effect of different current tab arrangements on the impedance spectra is analyzed and possible electrochemical causes are discussed. In a second step, one terminal is used to apply a sinusoidal current while the other terminals are used to monitor the local potential distribution at different positions along the electrodes of the cell. It is observed that the characteristic decay of the voltage amplitude along the electrode changes non-linearly with frequency, where high-frequent currents experience a stronger attenuation along the current collector than low-frequent currents. In further experiments, the decay characteristic is controlled by the cell temperature, driven by the increasing resistance of the current collector and the enhanced kinetic and transport properties of the active material and electrolyte. Measurements indicate that the ac current distribution depends strongly on the frequency and the temperature. In this context, the challenges for electrochemical impedance spectroscopy as cell diagnostic technique for commercial cells are discussed.

  13. An efficient current-based logic cell model for crosstalk delay analysis

    Science.gov (United States)

    Nazarian, Shahin; Das, Debasish

    2013-04-01

    Logic cell modelling is an important component in the analysis and design of CMOS integrated circuits, mostly due to nonlinear behaviour of CMOS cells with respect to the voltage signal at their input and output pins. A current-based model for CMOS logic cells is presented, which can be used for effective crosstalk noise and delta delay analysis in CMOS VLSI circuits. Existing current source models are expensive and need a new set of Spice-based characterisation, which is not compatible with typical EDA tools. In this article we present Imodel, a simple nonlinear logic cell model that can be derived from the typical cell libraries such as NLDM, with accuracy much higher than NLDM-based cell delay models. In fact, our experiments show an average error of 3% compared to Spice. This level of accuracy comes with a maximum runtime penalty of 19% compared to NLDM-based cell delay models on medium-sized industrial designs.

  14. Solar cells with distributed parameters: Current-voltage characteristics under uniform and nonuniform illumination

    Science.gov (United States)

    Aripov, K. K.; Rumyantsev, V. D.

    1984-02-01

    A simple method of calculating the current voltage characteristics of solar cells, based on an equivalent resistance diode ladder network with stripline contacts, is applied to such cells with uniform thickness and various shapes of the active surface. Distributed resistance are represented by equivalent lumped ones. This procedure is applied first to the case of uniform illumination, using measured current voltage characteristics of cells and very precisely piecewise linearly approximated exponential current voltage characteristics of diodes. In the case of nonuniform illumination the latter is assumed to be axisymmetric, with the surface consisting of completely dark and uniformly bright segments. Numerical data is generated on this basis for GaAs cells of rectangular or sectoral shape uniformly illuminated and in the shape of circular disks either completely uniformly illuminated or with various configurations of concentric dark and bright zones. Nonuniform illumination is found to result in a flatter current voltage characteristic with a lower open circuit voltage.

  15. 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.

  16. 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.

  17. 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.

  18. Simulation of forward dark current voltage characteristics of tandem solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Rubinelli, F.A., E-mail: pancho@ceride.gov.ar

    2012-04-30

    The transport mechanisms tailoring the shape of dark current-voltage characteristics of amorphous and microcrystalline silicon based tandem solar cell structures are explored with numerical simulations. Our input parameters were calibrated by fitting experimental current voltage curves of single and double junction structures measured under dark and illuminated conditions. At low and intermediate forward voltages the dark current-voltage characteristics show one or two regions with a current-voltage exponential dependence. The diode factor is unique in tandem cells with the same material in both intrinsic layers and two dissimilar diode factors are observed in tandem cells with different materials on the top and bottom intrinsic layers. In the exponential regions the current is controlled by recombination through gap states and by free carrier diffusion. At high forward voltages the current grows more slowly with the applied voltage. The current is influenced by the onset of electron space charge limited current (SCLC) in tandem cells where both intrinsic layers are of amorphous silicon and by series resistance of the bottom cell in tandem cells where both intrinsic layers are of microcrystalline silicon. In the micromorph cell the onset of SCLC becomes visible on the amorphous top sub-cell. The dark current also depends on the thermal generation of electron-hole (e-h) pairs present at the tunneling recombination junction. The highest dependence is observed in the tandem structure where both intrinsic layers are of microcrystalline silicon. The prediction of meaningless dark currents at low forward and reverse voltages by our code is discussed and one solution is given. - Highlights: Black-Right-Pointing-Pointer Transport mechanisms shaping the dark current-voltage curves of tandem devices. Black-Right-Pointing-Pointer The devices are amorphous and microcrystalline based tandem solar cells. Black-Right-Pointing-Pointer Two regions with a current-voltage exponential

  19. 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.

  20. 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.

  1. 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.

  2. [Induced pluripotent stem (iPS) cell-based cell therapy for muscular dystrophy: current progress and future prospects].

    Science.gov (United States)

    Nishiyama, Takashi; Takeda, Shin'ichi

    2012-01-01

    Duchenne muscular dystrophy (DMD) is a devastating muscle disorder caused by mutations in the dystrophin gene. There is currently no effective treatment for DMD. Muscle satellite cells are tissue-specific stem cells found in the skeletal muscle; these cells play a central role in postnatal muscle growth and regeneration, and are, therefore, a potential source for stem cell therapy for DMD. However, transplantation of satellite cell-derived myoblasts has not yet been successful in humans. Patient-specific induced pluripotent stem (iPS) cells are expected to be a source for autologous cell transplantation therapy for DMD, because iPS cells can proliferate vigorously in vitro and can differentiate into multiple cell lineages both in vitro and in vivo. Here, we discuss the strategies to generate muscle stem cells from iPS cells. So far, the most promising method for generating muscle stem cells from iPS cells is the conditional overexpression of Pax3 or Pax7 in the differentiating mouse embryoid bodies. However, induction methods for human iPS cells have not yet been developed. Thus, iPS cells are expected to serve as an in vitro disease model system, which will enable us to determine the pathology of muscle diseases and develop pharmaceutical treatments. PMID:22223500

  3. 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.

  4. Microstructural Degradation of Ni/YSZ Electrodes in Solid Oxide Electrolysis Cells under High Current

    DEFF Research Database (Denmark)

    Chen, Ming; Liu, Yi-Lin; Bentzen, Janet Jonna;

    2013-01-01

    Ni/yttria stabilized zirconia (YSZ) supported solid oxide electrolysis cells (SOECs) were exposed to long-term galvanostatic electrolysis tests, under different testing conditions (temperature, gas composition, current density etc.) with an emphasis on high current density (above −1 A/cm2...

  5. 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.

  6. Exploring dark current voltage characteristics of micromorph silicon tandem cells with computer simulations

    NARCIS (Netherlands)

    Sturiale, A.; Li, H. B. T.; Rath, J.K.; Schropp, R.E.I.; Rubinelli, F.A.

    2009-01-01

    The transport mechanisms controlling the forward dark current-voltage characteristic of the silicon micromorph tandem solar cell were investigated with numerical modeling techniques. The dark current-voltage characteristics of the micromorph tandem structure at forward voltages show three regions: t

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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...

  12. Adult human neural stem cell therapeutics: Current developmental status and prospect

    OpenAIRE

    Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as ce...

  13. The Probabilistic Niche Model Reveals the Niche Structure and Role of Body Size in a Complex Food Web

    OpenAIRE

    Richard J Williams; Ananthi Anandanadesan; Drew Purves

    2010-01-01

    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 w...

  14. 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...... 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...

  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. 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.

  17. 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...... dynamics, as well as a battery model based on an equivalent circuit model and a balance of plant power consumption model. The models are tuned with experimental data and verified using a verification data set. The model is used to develop an output current controller which can control the charge current...... of the battery. The controller is a PI controller with feedforward and anti-windup. The performance of the controller is tested and verified on the physical system....

  18. Simulation of forward dark current voltage characteristics of tandem solar cells

    International Nuclear Information System (INIS)

    The transport mechanisms tailoring the shape of dark current–voltage characteristics of amorphous and microcrystalline silicon based tandem solar cell structures are explored with numerical simulations. Our input parameters were calibrated by fitting experimental current voltage curves of single and double junction structures measured under dark and illuminated conditions. At low and intermediate forward voltages the dark current–voltage characteristics show one or two regions with a current–voltage exponential dependence. The diode factor is unique in tandem cells with the same material in both intrinsic layers and two dissimilar diode factors are observed in tandem cells with different materials on the top and bottom intrinsic layers. In the exponential regions the current is controlled by recombination through gap states and by free carrier diffusion. At high forward voltages the current grows more slowly with the applied voltage. The current is influenced by the onset of electron space charge limited current (SCLC) in tandem cells where both intrinsic layers are of amorphous silicon and by series resistance of the bottom cell in tandem cells where both intrinsic layers are of microcrystalline silicon. In the micromorph cell the onset of SCLC becomes visible on the amorphous top sub-cell. The dark current also depends on the thermal generation of electron–hole (e–h) pairs present at the tunneling recombination junction. The highest dependence is observed in the tandem structure where both intrinsic layers are of microcrystalline silicon. The prediction of meaningless dark currents at low forward and reverse voltages by our code is discussed and one solution is given. - Highlights: ► Transport mechanisms shaping the dark current-voltage curves of tandem devices. ► The devices are amorphous and microcrystalline based tandem solar cells. ► Two regions with a current-voltage exponential dependence are observed. ► The tandem J-V diode factor is the

  19. Combined local current distribution measurements and high resolution neutron radiography of operating Direct Methanol Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Alexander; Wippermann, Klaus; Mergel, Juergen; Lehnert, Werner; Stolten, Detlef [Institute of Energy Research, IEF-3: Fuel Cells, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Sanders, Tilman; Baumhoefer, Thorsten; Sauer, Dirk U. [Institute for Power Electronics and Electrical Drives (ISEA), RWTH Aachen University, Jaegerstrasse 17-19, 52066 Aachen (Germany); Manke, Ingo; Banhart, John [Institute of Materials Science and Technology, Berlin Institute of Technology, Hardenbergstrasse 36, 10623 Berlin (Germany); Helmholtz Centre Berlin (Hahn-Meitner-Institute), SF3, Glienicker Strasse 100, 14109 Berlin (Germany); Kardjilov, Nikolay; Hilger, Andre; Schloesser, Jana [Helmholtz Centre Berlin (Hahn-Meitner-Institute), SF3, Glienicker Strasse 100, 14109 Berlin (Germany); Hartnig, Christoph [Centre for Solar Energy and Hydrogen Research (ZSW), Helmholtzstrasse 8, 89081 Ulm (Germany)

    2009-08-15

    The current and fluid distribution in Direct Methanol Fuel Cells (DMFCs) was investigated in situ by means of combined high resolution neutron radiography and locally resolved current distribution measurements. The used neutron radiography set-up allows high spatial resolutions down to 70 {mu}m at the full test cell area. A local formation of water droplets in the cathode flow field channels could be observed. Strongly inhomogeneous current distributions during cathodic flooding processes result in a performance loss of up to 30% of the initial value. Single CO{sub 2} bubbles can be observed at low current densities. The water and current distribution during bi-functional operation of a DMFC was measured for the first time. (author)

  20. 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.

  1. Development of a laboratory niche Web site.

    Science.gov (United States)

    Dimenstein, Izak B; Dimenstein, Simon I

    2013-10-01

    This technical note presents the development of a methodological laboratory niche Web site. The "Grossing Technology in Surgical Pathology" (www.grossing-technology.com) Web site is used as an example. Although common steps in creation of most Web sites are followed, there are particular requirements for structuring the template's menu on methodological laboratory Web sites. The "nested doll principle," in which one object is placed inside another, most adequately describes the methodological approach to laboratory Web site design. Fragmentation in presenting the Web site's material highlights the discrete parts of the laboratory procedure. An optimally minimal triad of components can be recommended for the creation of a laboratory niche Web site: a main set of media, a blog, and an ancillary component (host, contact, and links). The inclusion of a blog makes the Web site a dynamic forum for professional communication. By forming links and portals, cloud computing opens opportunities for connecting a niche Web site with other Web sites and professional organizations. As an additional source of information exchange, methodological laboratory niche Web sites are destined to parallel both traditional and new forms, such as books, journals, seminars, webinars, and internal educational materials. PMID:23769601

  2. 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.

  3. An emerging niche market opportunity. Part I.

    Science.gov (United States)

    Pulaski, M J

    1997-01-01

    Society is split between a desire for access to quality health care and a reluctance, by some, to pay for it. Looking at this cost/access dichotomy historically enables one to recognize an emerging niche market--discriminating, affluent consumers willing to pay for better health care. PMID:10169123

  4. 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.

  5. Simulation and optimization of current matching double-junction InGaN/Si solar cells

    Science.gov (United States)

    Nacer, S.; Aissat, A.

    2016-02-01

    This paper deals with theoretical investigation of the performance of current-matched In x GaN/Si double-junction solar cells. Calculations were performed under 1-sun AM1.5 using the one diode ideal model. Impact of minor carrier lifetime and surface recombination velocity in the top sub-cell on the cell performances is analyzed. Optimum composition of the top sub-cell has been identified ( x = 51.8 % and E g = 1.68 eV). The simulation results predict, for the optimized InGaN/Si double-junction solar cell, a short-circuit current J sc = 20 mA/cm2, an open-circuit voltage V oc = 1.97 V, and a conversion efficiency η = 38.3%.

  6. 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.

  7. 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.

  8. Adult Neurogenesis: Ultrastructure of a Neurogenic Niche and Neurovascular Relationships

    OpenAIRE

    Paula Grazielle Chaves da Silva; Jeanne L Benton; Beltz, Barbara S.; Silvana Allodi

    2012-01-01

    The first-generation precursors producing adult-born neurons in the crayfish (Procambarus clarkii) brain reside in a specialized niche located on the ventral surface of the brain. In the present work, we have explored the organization and ultrastructure of this neurogenic niche, using light-level, confocal and electron microscopic approaches. Our goals were to define characteristics of the niche microenvironment, examine the morphological relationships between the niche and the vasculature an...

  9. Current Challenges in Cell-Type Discovery Through Single-Cell Data

    Directory of Open Access Journals (Sweden)

    De Vargas Roditi Laura

    2015-01-01

    Full Text Available Single cell sequencing and proteome profiling efforts in the past few years have revealed widespread genetic and proteomic heterogeneity among tumor cells. However, sensible cell-type definition of such heterogeneous cell populations has so far been a challenging task. Single cell technologies such as RNA sequencing and mass cytometry provide information precluded by conventional bulk measurements and have achieved significant improvements in multiparametricity at high cellular throughput. By combining these technologies with computational and mathematical techniques it is possible to quantitatively define cellular heterogeneity, uncovering distinct phenotypic profiles that can be utilized to, for example, characterize tumor heterogeneity with the potential to develop and improve therapeutic strategies.

  10. St. Mary's Collegiate Church, Youghal, north choir wall, tomb niche, base of niche

    OpenAIRE

    O'Donovan, Danielle

    2005-01-01

    Base of tomb niche opening, moulding from top down comprises: roll, roll, bell, roll, roll, bell, curved plinth. Very unusual Perpendicular style base, other examples can be found at Strade, Sligo Dominican, Balintubber.

  11. The influence of the pre-metastatic niche on breast cancer metastasis.

    Science.gov (United States)

    Ursini-Siegel, Josie; Siegel, Peter M

    2016-09-28

    The emergence of metastatic disease constitutes a significant life-threatening development during cancer progression. To date, intensive efforts have been focused on understanding the intrinsic properties that confer malignant potential to cancer cells, as well as the role of the primary tumour microenvironment in promoting cancer metastasis. Beyond events occurring at the primary site, the metastatic cascade is composed of numerous barriers that must be overcome in order for disseminating cancer cells to form distal metastases. The most formidable of these is the ability of cancer cells to seed and grow in a completely foreign microenvironment. Interestingly, solid malignancies often display a particular tropism for specific tissue sites. For example, breast patients with metastatic disease will often develop bone, lung, liver or brain metastases. This mini-review will explore aspects of pre-existing and induced metastatic niches and focus on how the unique composition and function of diverse niche components, within common sites of breast cancer metastasis, enable the survival and growth of disseminated cancer cells. These common supportive functions of the niche are provided by a complex array of stromal components and molecular mechanisms that are, in part, reflective of the tissue in which the metastases arise. Finally, the metastatic niche is a dynamic structure that is continually altered and sculpted by the cancer cells during progression of the metastatic lesion. PMID:26577808

  12. 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.

  13. Intestinal stem cell response to injury: lessons from Drosophila.

    Science.gov (United States)

    Jiang, Huaqi; Tian, Aiguo; Jiang, Jin

    2016-09-01

    Many adult tissues and organs are maintained by resident stem cells that are activated in response to injury but the mechanisms that regulate stem cell activity during regeneration are still poorly understood. An emerging system to study such problem is the Drosophila adult midgut. Recent studies have identified both intrinsic factors and extrinsic niche signals that control the proliferation, self-renewal, and lineage differentiation of Drosophila adult intestinal stem cells (ISCs). These findings set up the stage to interrogate how niche signals are regulated and how they are integrated with cell-intrinsic factors to control ISC activity during normal homeostasis and regeneration. Here we review the current understanding of the mechanisms that control ISC self-renewal, proliferation, and lineage differentiation in Drosophila adult midgut with a focus on the niche signaling network that governs ISC activity in response to injury. PMID:27137186

  14. Current Stem Cell Biomarkers and Their Functional Mechanisms in Prostate Cancer

    Science.gov (United States)

    Zhang, Kaile; Zhou, Shukui; Wang, Leilei; Wang, Jianlong; Zou, Qingsong; Zhao, Weixin; Fu, Qiang; Fang, Xiaolan

    2016-01-01

    Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells) might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients. PMID:27447616

  15. 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.

  16. 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)

  17. Fluctuations of the peak current of tunnel diodes in multi-junction solar cells

    International Nuclear Information System (INIS)

    Interband tunnel diodes are widely used to electrically interconnect the individual subcells in multi-junction solar cells. Tunnel diodes have to operate at high current densities and low voltages, especially when used in concentrator solar cells. They represent one of the most critical elements of multi-junction solar cells and the fluctuations of the peak current in the diodes have an essential impact on the performance and reliability of the devices. Recently we have found that GaAs tunnel diodes exhibit extremely high peak currents that can be explained by resonant tunnelling through defects homogeneously distributed in the junction. Experiments evidence rather large fluctuations of the peak current in the diodes fabricated from the same wafer. It is a challenging task to clarify the reason for such large fluctuations in order to improve the performance of the multi-junction solar cells. In this work we show that the large fluctuations of the peak current in tunnel diodes can be caused by relatively small fluctuations of the dopant concentration. We also show that the fluctuations of the peak current become smaller for deeper energy levels of the defects responsible for the resonant tunnelling.

  18. Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis-Masters of Survival and Clonality?

    Science.gov (United States)

    Pleyer, Lisa; Valent, Peter; Greil, Richard

    2016-01-01

    Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the "reprogramming" of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs. PMID:27355944

  19. Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

    Directory of Open Access Journals (Sweden)

    Lisa Pleyer

    2016-06-01

    Full Text Available Myelodysplastic syndromes (MDS are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML. Accumulating evidence suggests that the altered bone marrow (BM microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the “reprogramming” of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs.

  20. Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

    Science.gov (United States)

    Pleyer, Lisa; Valent, Peter; Greil, Richard

    2016-01-01

    Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the “reprogramming” of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs. PMID:27355944

  1. 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

  2. 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. PMID:26096695

  3. Market positioning: the shifting effects of niche overlap

    NARCIS (Netherlands)

    J. Bruggeman; D. Grunow; M.A.A.M. Leenders; I. Vermeulen; J.G. Kuilman

    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

  4. 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.

  5. Current Status of Human Adipose–Derived Stem Cells: Differentiation into Hepatocyte-Like Cells

    Directory of Open Access Journals (Sweden)

    Feras Al Battah

    2011-01-01

    Full Text Available The shortage of human organ donors and the low cell quality of available liver tissues represent major obstacles for the clinical application of orthotropic liver transplantation and hepatocyte transplantation, respectively. Therefore, worldwide research groups are investigating alternative extrahepatic cell sources. Recent in vitro studies have demonstrated that mesenchymal stem cells (MSCs from various sources, including human bone marrow, adipose tissue, and umbilical cord, can be differentiated into hepatocyte-like cells when appropriate conditions are used. In particular, interest exists for human adipose–derived stems cells (hASCs as an attractive cell source for generating hepatocyte-like cells. The hASCs are multipotent MSCs that reside in adipose tissue, with the ability to self-renew and differentiate into multiple cell lineages. Moreover, these cells can secrete multiple growth factors and cytokines that exert beneficial effects on organ or tissue injury. In this review, we will not only present recent data regarding hASC biology, their isolation, and differentiation capability towards hepatocytes, but also the potential application of hASC-derived hepatocytes to study drug toxicity. Additionally, this review will discuss the therapeutic potential of hASCs as undifferentiated cells in liver regeneration.

  6. Current Status of Human Adipose–Derived Stem Cells: Differentiation into Hepatocyte-Like Cells

    OpenAIRE

    Feras Al Battah; Joery De Kock; Tamara Vanhaecke; Vera Rogiers

    2011-01-01

    The shortage of human organ donors and the low cell quality of available liver tissues represent major obstacles for the clinical application of orthotropic liver transplantation and hepatocyte transplantation, respectively. Therefore, worldwide research groups are investigating alternative extrahepatic cell sources. Recent in vitro studies have demonstrated that mesenchymal stem cells (MSCs) from various sources, including human bone marrow, adipose tissue, and umbilical cord, can be differe...

  7. Dreams, Devices, Niches, and Edges: Coping with the Changing Landscape of Information Technology.

    Science.gov (United States)

    Crawford, Walt

    1993-01-01

    Reflects on changes in information technology and current and possible future trends. Topics discussed include technological innovations and their chances for success; information technology devices; finding market niches; and implications for libraries, including the future of print books and projections of electronic access and publishing. (LRW)

  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. 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.

  10. 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.

  11. Incremental by Design? On the Role of Incumbents in Technology Niches

    DEFF Research Database (Denmark)

    Hain, Daniel S.; Jurowetzki, Roman

    In this paper, we study structural dynamics and path dependencies of research networks in technological niches at the case of public funded research projects. We particularly investigate which benefits large incumbent firms enjoy in the formation of such networks, and discuss possible implications...... for the rate and direction of technological progress as an outcome. Literature on sustainability transitions outlines the significance of niches and protected space for the development of path-breaking technologies in early stages. They are said to offer firms an environment to experiment in joint learning...... 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...

  12. Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine.

    Science.gov (United States)

    Arab, Sonja F; Düwel, Philip; Jüngling, Eberhard; Westhofen, Martin; Lückhoff, Andreas

    2004-06-01

    Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Meniere's disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca2+ channels, may directly target vestibular hair cells where Ca2+ currents are important for the mechano-electrical transduction and transmitter release. Our aim was to clarify whether cinnarizine affected voltage-dependent Ca2+ currents in vestibular type II hair cells. Such cells were isolated from inner ears of guinea pigs by enzymatic and mechanical dissection from the gelatinous otolithic membrane and studied with the patch-clamp technique in conventional whole-cell mode. Ca2+ currents were elicited by depolarizing pulses in a solution containing 1.8 mM Ca2+ and 40 mM Ba2+. These currents resembled L-type currents (I(Ca,L)) with respect to their voltage-dependence and their inhibition by nifedipine and Cd2+ but did not show time-dependent inactivation. The currents were inhibited by cinnarizine in a concentration-dependent and reversible manner. The IC50 was 1.5 microM. A block exceeding 80% was achieved with 10 microM. The onset of current block was faster with higher concentrations but the reversibility after wash-out was less, suggesting accumulation in the membrane. We conclude that these direct actions of cinnarizine on hair cells should be considered as molecular mechanisms contributing to therapeutic effects of cinnarizine in vertigo. PMID:15138660

  13. 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.

  14. 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.

  15. 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.

  16. Current status of gene transfer into haemopoietic progenitor cells: application to Langerhans cell histiocytosis.

    OpenAIRE

    M. Brenner

    1994-01-01

    A number of recent studies have shown that it is possible to obtain significant levels of gene transfer and expression in marrow progenitor cells and their progeny by using retroviral vectors. The data obtained from these studies and the possible applications to Langerhans cell histiocytosis (LCH) are reviewed.

  17. 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.

  18. 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.

  19. 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.

  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...