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Stem Cell Niche (stem + cell_niche)
Selected AbstractsPolymeric Aqueous Biphasic Systems for Non-Contact Cell Printing on Cells: Engineering Heterocellular Embryonic Stem Cell NichesADVANCED MATERIALS, Issue 24 2010Hossein Tavana An optimized polymeric aqueous two-phase system allows direct and non-contact printing of cells onto a monolayer of living cells in arbitrary shapes as well as in a high-density microarray format to create heterocellular microenvironments and study the effect of direct cell,cell interactions on cell fate. The entire process is performed in aqueous media to support full cell viability and functionality. [source] Artificial Stem Cell Niches,ADVANCED MATERIALS, Issue 32-33 2009Matthias P. Lutolf Abstract 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-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such "artificial niches" constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. [source] The Hydra polyp: Nothing but an active stem cell communityDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2010Thomas C. G. Bosch Hydra is a powerful stem cell model because its potential immortality and extensive regeneration capacity is due to the presence of three distinct stem cell lineages. All three lineages conform to a well-defined spatial distribution across the whole body column of the polyp. Stem cell function in Hydra is controlled by extracellular cues and intrinsic genetic programs. This review focuses on the elusive stem cell niche of the epithelial layers. Based on a comparison of the differences between, and commonalities among, stem cells and stem cell niches in Hydra and other invertebrates and vertebrates, we propose that the whole body column of the polyp may be considered a stem cell "niche" in which stem cell populations are established and signals ensuring the proper balance between stem cells and progenitor cells are integrated. We show that, at over 500 million years old, Hydra offers an early glimpse of the regulatory potential of stem cell niches. [source] Development of Live Cell Chips to Monitor Cell Differentiation ProcessesENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 1 2008C. Maercker Abstract A big demand exists for high-throughput functional in vitro assays which can measure cellular phenotypes by molecular methods and therefore improve the resources of primary cells for cell therapy, tissue engineering and high-content screenings in drug development. This approach focuses on cellular adhesion which is an important differentiation process during homing of stem cells. Moreover, it is a promising method especially for adherent cells which are not accessible by classical cell sorting methods. The chip design includes a housing with electrodes to measure electric field densities and impedance, respectively. Moreover, specific coatings of the wells permit a perfect growth of the selected cell types. In parallel, protein biomarkers can be followed by light microscopy. So far, experiments have been started to discriminate between different cell densities and cell types. In addition, after stimulating human cardiac fibroblasts and human umbilical vein endothelial cells, concentrations of proteins involved in adhesion had been increased, and proteins were translocated within the cells. In ongoing experiments, different human cell lines and fibroblastoid mesenchymal stem cells isolated from fat tissue, umbilical cord, or bone marrow are tested in the chip. To optimize the adhesion conditions, the surfaces within the vials of the chip were specifically activated. Microscopy was adjusted to be able to measure cellular morphology in parallel. This concept allows to identify the behavior of mesenchymal stem cells, which cannot be described so far by standard biomarkers. In addition, simulation of the homing process of the cells within its stem cell niche in an in vitro assay is a promising setup for large-scale gain-of-function or loss-of-function screenings in functional genomics as well as for generating precursor cells relevant for the therapy of various diseases. [source] Artificial Stem Cell Niches,ADVANCED MATERIALS, Issue 32-33 2009Matthias P. Lutolf Abstract 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-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such "artificial niches" constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. [source] Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope imagesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2010Mihaela Gherghiceanu Abstract A highly heterogeneous population of stem and progenitor cells has been described by light immunohistochemistry in the mammalian adult heart, but the ultrastructural identity of cardiac stem cells remains unknown. Using electron microscopy, we demonstrate the presence of cells with stem features in the adult mouse heart. These putative cardiac stem cells are small (6,10 ,m), round cells, with an irregular shaped nucleus, large nucleolus, few endoplasmic reticulum cisternae and mitochondria, but numerous ribosomes. Stem cells located in the epicardial stem cell niche undergo mitosis and apoptosis. Cells with intermediate features between stem cells and cardiomyocyte progenitors have also been seen. Moreover, electron microscopy showed that cardiomyocyte progenitors were added to the peripheral working cardiomyocytes. Telocytes make a supportive interstitial network for stem cells and progenitors in the stem cell niche. This study enhances the hypothesis of a unique type of cardiac stem cell and progenitors in different stages of differentiation. In our opinion, stem cells, cardiomyocyte progenitors and telocytes sustain a continuous cardiac renewal process in the adult mammalian heart. [source] Ex vivo organ culture of adipose tissue for in situ mobilization of adipose-derived stem cells and defining the stem cell nicheJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Young-Il Yang In spite of the advances in the knowledge of adipose-derived stem cells (ASCs), in situ location of ASCs and the niche component of adipose tissue (AT) remain controversial due to the lack of an appropriate culture system. Here we describe a fibrin matrix-supported three-dimensional (3D) organ culture system for AT which sustains the ASC niche and allows for in situ mobilization and expansion of ASCs in vitro. AT fragments were completely encapsulated within the fibrin matrix and cultured under dynamic condition. The use of organ culture of AT resulted in a robust outgrowth and proliferation in the fibrin matrix. The outgrown cells were successfully recovered from fibrin by urokinase treatment. These outgrown cells fulfilled the criteria of mesenchymal stem cells, adherence to plastic, multilineage differentiation, and cell surface molecule expression. In vitro label retaining assay revealed that newly divided cells during the culture resided in interstitium between adipocytes and capillary endothelial cells. These interstitial stromal cells proliferated and outgrew into the fibrin matrix. Both in situ mobilized and outgrown cells expressed CD146 and ,-smooth muscle actin (SMA), but no endothelial cell markers (CD31 and CD34). The structural integrity and spatial approximation of CD31,/CD34,/CD146+/SMA+ interstitial stromal cells, adipocytes, and capillary endothelial cells were well preserved during in vitro culture. Our results suggest that ASCs are natively associated with the capillary wall and more specifically, belong to a subset of pericytes. Furthermore, organ culture of AT within a fibrin matrix-supported 3D environment can recapitulate the ASC niche in vitro. J. Cell. Physiol. 224: 807,816, 2010. © 2010 Wiley-Liss, Inc. [source] Stem cells in pathobiology and regenerative medicine,THE JOURNAL OF PATHOLOGY, Issue 2 2009MR Alison Abstract This issue of the Journal of Pathology contains 16 articles largely dealing with the role of tissue-specific adult stem cells in the pathogenesis of disease, notably cancer. These authoritative reviews begin by describing the current knowledge regarding the identity and molecular regulation of normal tissue-specific stem cells, before itemizing their role in the aetiology and progression of disease. Fundamental concepts regarding the stem cell niche have been gleaned from studies of germ line stem cells in Drosophila and Caenorhabditis elegans, and these are described in detail in this issue. Somatic cell reprogramming, a process underlying not only therapeutic cloning but also the production of induced pluripotent stem (iPS) cells, is further discussed. Much attention is given to embryonic stem (ES) and iPS cells within the scientific community; this issue of the Journal of Pathology redresses this imbalance by illustrating the pivotal role of adult stem cells in much of human disease. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Spindles losing their bearings: Does disruption of orientation in stem cells predict the onset of cancer?BIOESSAYS, Issue 6 2010Trevor A. Graham Abstract Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti-tumourigenic mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers. [source] Haematopoietic stem cell niche in DrosophilaBIOESSAYS, Issue 8 2007Ute Koch Development and homeostasis of the haematopoietic system is dependent upon stem cells that have the unique ability to both self-renew and to differentiate in all cell lineages of the blood. The crucial decision between haematopoietic stem cell (HSC) self-renewal and differentiation must be tightly controlled. Ultimately, this choice is regulated by the integration of intrinsic signals together with extrinsic cues provided by an exclusive microenvironment, the so-called haematopoietic niche. Although the haematopoietic system of vertebrates has been studied extensively for many decades, the specification of the HSC niche and its signals involved are poorly understood. Much of our current knowledge of how niches regulate long-term maintenance of stem cells is derived from studies on Drosophila germ cells. Now, two recently published studies by Mandal et al.1 and Krezmien et al.2 describe the Drosophila haematopoietic niche and signal transduction pathways that are involved in the maintenance of haematopoietic precursors. Both reports emphasize several features that are important for controlling stem cell behavior and show parallels to both the vertebrate haematopoietic niche as well as the Drosophila germline stem cell niches in ovary and testis. The findings of both papers shed new light on the specific interactions between haematopoietic progenitors and their microenvironment. BioEssays 29:713,716, 2007. © 2007 Wiley Periodicals, Inc. [source] Lhx2,decisive role in epithelial stem cell maintenance, or just the "tip of the iceberg"?BIOESSAYS, Issue 12 2006Stephan Tiede Stem cell self renewal, maintenance and differentiation are influenced by the convergence of intrinsic cellular signals and extrinsic microenvironmental cues from the surrounding stem cell niche. However, the specific signals involved are often still poorly understood. This is also true for skin epithelial stem cells. Recently, by transcriptionally profiling of embryonic hair progenitors in mice, Rhee et al.1 have managed to define how murine hair follicle epithelial stem cells are specified and maintained in an undifferentiated state. These authors have identified Lhx2 as a transcription factor functionally positioned downstream of signals necessary to specify hair follicle stem cells such as p63 or NF,B, but upstream of signals like Wnt/,-catenin, Bmp or Shh that are required to drive activated stem cells via the production of transient amplifying cells into terminal differentiation. BioEssays 28: 1157,1160, 2006. © 2006 Wiley Periodicals, Inc. [source] Controlling the stem cell niche: right time, right place, right strengthBIOESSAYS, Issue 1 2006Catherin Niemann Wnt signalling through ,-catenin plays a pivotal role during embryonic pattern formation, cell fate determination and tissue homeostasis in the adult organism. In the skin, as in many other tissues, Wnt/,-catenin signalling can control lineage determination and differentiation. However, it was not known whether Wnt/,-catenin signalling is an immediate regulator of the stem cell niche in skin tissue. A recent publication now provides evidence that Wnt/,-catenin signalling exerts a direct effect on the stem cell compartment by inducing quiescent stem cells to enter the cell cycle during early stages of hair follicle regeneration. In addition, the authors demonstrate that ,-catenin is required for maintenance of the stem cell pool in the tissue.1 The data suggest that a gradient in Wnt/,-catenin activity levels can induce different responses within distinct cell populations reflected by activation of distinct transcriptional profiles. BioEssays 28:1,5, 2006. © 2005 Wiley Periodicals, Inc. [source] 2332: Pathological changes of anatomical structure and markers of limbal stem cell niche due to inflammationACTA OPHTHALMOLOGICA, Issue 2010C CURCIO Purpose It's known that severe inflammatory processes may cause limbal stem cell (SC) deficiency decreasing the number of SC niches and changing the microanatomy of these structures. Methods The aim of this study was to evaluate the expression of different SC markers in normal human limbus and to study how an inflammatory conditions can modulate these antigens. To understand the pathological changes in limbal crypts structure due to severe inflammation, a case of corneal melting and perforation in advanced herpes simplex (HSV) disease, two cases of endophthalmitis and a case of fungal infection were analyzed.Samples were examined by immunohistochemistry or immunofluorescence for p63, vimentin, laminin5, integrin (Int) ,6, int ,1, int ,4, ABCG2, desmoglein 3, connexin43, N-cadherin and cytokeratin (K) 12 positivity. We evaluated the anatomical structure of limbal crypts in each case and the positivity for SC marker used to identify SC. Results In normal limbus, the investigated SC markers were positive. In the HSV we didn't observe presence of crypts, whereas in both cases of endophthalmitis crypts were still present but they had an atypical structure: the basal cells in the crypts were "stretched" and endowed by inflammatory cells. In the pathological cases, we observed positivity for K12 while, among SC markers, p63, ABCG2 and connexin43 were still present; the others antigens were variably expressed. Conclusion Different pathologies involving the limbus may result in marked chenges of expression of SC markers within the crypts. [source] Characterization within and around the Limbal Epithelial CryptACTA OPHTHALMOLOGICA, Issue 2007AM YEUNG Purpose: The Limbal Epithelial Crypt (LEC) is an anatomical structure that is found between the junction of the cornea and sclera and is in a unique position to make it an ideal structure to examine further. Previous studies have demonstrated the LEC to have properties that suggest it may be a stem cell niche. Basal cells of the LEC are significantly smaller than basal cells found in adjacent rete pegs, and morphologically they have a higher nuclear:cytoplasmic ratio. We set out to examine LEC further by exploring the surrounding LEC matrix proteins, and with known differentiation markers. Methods: Donated corneo-sclero rims were cut into eight equal sized pieces and frozen. Each piece was cut into 7,m serial sections, and was examined by microscopy for LEC structures. Identified LEC was collected on slides and stored until they were fixed in acetone and processed by standard immunofluorescence techniques for each differentiation marker. Results: Tenacin C was more positively taken up by the basement membrane of the LEC compared with the surrounding limbus. In addition, staining for desmoglein was negative against isolated small subpopulations of cells within the basal regions of the LEC. Conclusions: The LEC structure demonstrates properties that may identify this as a possible stem cell niche. Further studies are necessary to determine the significance of the LEC in its role in stem cell maintenance. [source] The Hydra polyp: Nothing but an active stem cell communityDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2010Thomas C. G. Bosch Hydra is a powerful stem cell model because its potential immortality and extensive regeneration capacity is due to the presence of three distinct stem cell lineages. All three lineages conform to a well-defined spatial distribution across the whole body column of the polyp. Stem cell function in Hydra is controlled by extracellular cues and intrinsic genetic programs. This review focuses on the elusive stem cell niche of the epithelial layers. Based on a comparison of the differences between, and commonalities among, stem cells and stem cell niches in Hydra and other invertebrates and vertebrates, we propose that the whole body column of the polyp may be considered a stem cell "niche" in which stem cell populations are established and signals ensuring the proper balance between stem cells and progenitor cells are integrated. We show that, at over 500 million years old, Hydra offers an early glimpse of the regulatory potential of stem cell niches. [source] Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical ApplicationsADVANCED MATERIALS, Issue 4 2010Thomas Boudou Abstract The design of advanced functional materials with nanometer- and micrometer-scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer-by-layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under "mild" conditions compatible with physiological media, capability of incorporating bioactive molecules, extra-cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio-temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusing molecules into films to control their internal structures or design "reservoirs," as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell "niches." [source] Artificial Stem Cell Niches,ADVANCED MATERIALS, Issue 32-33 2009Matthias P. Lutolf Abstract 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-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such "artificial niches" constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. [source] Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents,THE JOURNAL OF PATHOLOGY, Issue 1 2009DC Gilbert Abstract Interaction between the chemokine CXCL12 (SDF1) and the G-protein coupled receptor CXCR4 is responsible for the maintenance of adult stem cell niches and is known to play an important role in utero in the migration of primordial germ cells. We demonstrate expression of CXCL12 by Sertoli cells and confirm CXCR4 expression by the germ cell population of the adult human testes. CXCR4 is also known to mediate organ-specific patterns of metastases in a range of common cancers. We identify consistent expression of CXCR4 mRNA and protein in testicular germ cell tumours (TGCT) that accounts for their patterns of relapse in sites of known CXCL12 expression. Extragonadal primary germ cell tumours express CXCR4 and their sites of occurrence are coincident with areas of known CXCL12 expression in utero. We show that CXCL12 stimulates the invasive migration of a TGCT cell line in vitro in a CXCR4-dependent fashion and activates ERK. Furthermore, we demonstrate that expression of CXCL12 in stage I non-seminomas is significantly associated with organ-confined disease post-orchidectomy and reduced risk of relapse (p = 0.003). This may be through the loss of CXCL12 gradients that might otherwise attract cells away from the primary tumour. We propose CXCL12 expression as a potential predictor of subsequent relapse that could lead to avoiding unnecessary treatment and associated late toxicities. Our observations support a role for CXCL12/CXCR4 in the adult germ cell population and demonstrate pathological function in germ cell tumour development and metastasis that may have clinical utility. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Haematopoietic stem cell niche in DrosophilaBIOESSAYS, Issue 8 2007Ute Koch Development and homeostasis of the haematopoietic system is dependent upon stem cells that have the unique ability to both self-renew and to differentiate in all cell lineages of the blood. The crucial decision between haematopoietic stem cell (HSC) self-renewal and differentiation must be tightly controlled. Ultimately, this choice is regulated by the integration of intrinsic signals together with extrinsic cues provided by an exclusive microenvironment, the so-called haematopoietic niche. Although the haematopoietic system of vertebrates has been studied extensively for many decades, the specification of the HSC niche and its signals involved are poorly understood. Much of our current knowledge of how niches regulate long-term maintenance of stem cells is derived from studies on Drosophila germ cells. Now, two recently published studies by Mandal et al.1 and Krezmien et al.2 describe the Drosophila haematopoietic niche and signal transduction pathways that are involved in the maintenance of haematopoietic precursors. Both reports emphasize several features that are important for controlling stem cell behavior and show parallels to both the vertebrate haematopoietic niche as well as the Drosophila germline stem cell niches in ovary and testis. The findings of both papers shed new light on the specific interactions between haematopoietic progenitors and their microenvironment. BioEssays 29:713,716, 2007. © 2007 Wiley Periodicals, Inc. [source] In search for correlation among markers for limbal stem cells nicheACTA OPHTHALMOLOGICA, Issue 2009C CURCIO Purpose The corneoscleral limbus is known to be the site of corneal epithelial stem cells (SC). Several molecules have been proposed as SC markers but none of them is able to univocally identify them. The aim of this study was to evaluate co-expression of different SC markers in human limbus. Methods In this work five corneoscleral specimens from normal human donor eye-bank eyes (age 52-73 years) were fixed in formalin, divided in 8 segments, embedded in paraffin and examined by immunohistochemistry and immunofluorescence for p63, vimentin (vim), laminin 5, integrin (Int) ,6, Int ,1, Int ,4, connexin 43, ki67 and N-cadherin positivity. We firstly analyzed the distribution and the anatomical structure of limbal crypts in each of the segments. Then we evaluated the percentage of positive areas in the niches. Finally we looked for colocalizations and possible correlations among markers. Results We confirmed a different number of niches among the segments of the same corneoscleral rim. Moreover we observed high variability of niches number among patients which interestingly correlates with the percentage of p63 positivity of niche cells. Confocal microscopy double staining for p63 and vim did not show evident colocalization and vim + cells were seen in the superficial layers rather than in the deep layer of crypts. Int ,1 staining directly correlated with p63 positivity while the remaining proteins appeared variably and widely distributed Conclusion Colocalization was evident at least for two SC markers (Int ,1/p63) within the basal layers, while vim, expressed mainly in the superficial layers could act as late progenitor cell marker. [source] Artificial Stem Cell Niches,ADVANCED MATERIALS, Issue 32-33 2009Matthias P. Lutolf Abstract 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-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such "artificial niches" constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. [source] |