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Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

Lobba, A. R. M.; Forni, M. F.; Carreira, A. C. O.; Sogayar, Mari Cleide
Fonte: WILEY-BLACKWELL; HOBOKEN Publicador: WILEY-BLACKWELL; HOBOKEN
Tipo: Artigo de Revista Científica
ENG
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The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore...

Vitamin D deficiency in children and adolescents submitted to hematopoietic stem cell transplantation

Campos,Denise Johnsson; Biagini,Gleyne Lopes Kujew; Funke,Vaneuza Araujo Moreira; Bonfim,Carmem Maria Sales; Boguszewski,César Luiz; Borba,Victória Zeghbi Cochenski
Fonte: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Publicador: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2014 EN
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Background: Sub-optimal levels of vitamin D have been found to be highly prevalent in all age groups, with epidemiologic studies demonstrating a link between vitamin D deficiency and disease susceptibility, such as infection and cancer, and mortality rates. In adult transplant patients, it has been suggested that the immunomodulatory properties of vitamin D may have an important role in the prevention and treatment of graft-versus-host disease. Objective: The objective of this study was to assess serum 25-hydroxyvitamin D levels of children and adolescents submitted to allogeneic hematopoietic stem cell transplantation. Methods: Serum 25-hydroxyvitamin D levels of 66 patients, aged 4-20 years, were assessed at three stages: before hospitalization for hematopoietic stem cell transplantation and at 30 and 180 days after hematopoietic stem cell transplantation. The control group consisted of 25 healthy children. Results: At the pre-hematopoietic stem cell transplantation stage, patients had lower levels of 25-hydroxyvitamin D compared to controls (25.7 ± 12.3 ng/mL vs. 31.9 ± 9.9 ng/mL; p-value = 0.01), and a higher prevalence of 25-hydroxyvitamin D deficiency (32% vs. 8%; p-value = 0.01). Prevalence increased significantly after hematopoietic stem cell transplantation (p-value = 0.01) with half of the patients having vitamin D deficiency at 180 days after transplantation. At this stage...

The intestinal epithelial stem cell: the mucosal governor

POTTEN, CHRISTOPHER S. ; BOOTH, CATHERINE; PRITCHARD, D. MARK
Fonte: Blackwell Publishing Publicador: Blackwell Publishing
Tipo: Artigo de Revista Científica
Publicado em /08/1997 EN
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All epithelial cells in the small and large intestine are thought to originate from stem cells located towards the base of the crypts of Lieberkühn. To-date, there are no specific intestinal stem cell markers, hence stem cell properties can only be inferred. A range of experimental techniques have been employed including cell position mapping, radiation regeneration (clonogenic) assays, chimeric and transgenic mice. This review discusses the implications of experiments performed using these techniques in order to deduce the number, location and functional properties of stem cells. Stem cell homeostasis is maintained by cell proliferation and death ‘through apoptosis’. The various growth and matrix factors and genes which may control these processes, and be important for stem cell function, are discussed along with their carcinogenic and clinical implications.

Adult Stem Cell Therapy for Autoimmune Disease

Choi, Eun Wha
Fonte: Korean Society for Stem Cell Research Publicador: Korean Society for Stem Cell Research
Tipo: Artigo de Revista Científica
Publicado em /11/2009 EN
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Many studies of autologous hematopoietic stem cell transplantation (HSCT) and allogeneic HSCT have been conducted for autoimmune disease in various animal models. Because of the substantial risk of morbidity and mortality associated with allogeneic bone marrow transplantation, autologous transplants justified trying this approach in patient with severe autoimmune disease who were refractory to current treatments. Remission was achieved in some of the patients and some of them relapsed. Recently, many in vitro studies have reported that mesenchymal stem cells (MSC) have immunomodulatory properties and immunosuppressive effects on MHC-mismatched lymphocytes proliferation by inhibiting naïve, memory and activated T cells, B cell, NK cells and dendritic cells. In addition, adipose tissue-derived MSC (AT-MSC) are becoming an alternative source of MSC for therapeutic applications because adipose tissues are abundant, easily accessible, easily obtainable with little patient discomfort and large amounts of AT-MSC can be easily obtained. A large body of in vitro research has shown that AT-MSC have same or similar immunomodulatory effects with bone marrow derived MSC. Drawing on this finding, the increasing numbers of researchers have turned on their attention to preclinical studies on AT-MSC. As this new path of research evolves with subsequent reports...

Modulation of Stem Cell Differentiation with Biomaterials

Jang, Hyeon-Ki; Kim, Byung-Soo
Fonte: Korean Society for Stem Cell Research Publicador: Korean Society for Stem Cell Research
Tipo: Artigo de Revista Científica
Publicado em /05/2010 EN
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Differentiation of stem cells can be controlled with interactions with microenvironments of the stem cells. The interactions contain various signals including soluble growth factor signal, cell adhesion signal, and mechanical signal, which can modulate differentiation of stem cells. Biomaterials can provide these types of signals to induce desirable cellular differentiation. Biomaterials can deliver soluble growth factors locally to stem cells at a controlled rate for a long period. Stem cell adhesion to specific adhesion molecules presented by biomaterials can induce specific differentiation. Mechanical signals can be delivered to stem cells seeded onto biomaterial scaffolds. These approaches would be invaluable for direction of stem cell differentiation and in vivo tissue regeneration using stem cells.

Highly Upregulated Lhx2 in the Foxn1(^{−/−}) Nude Mouse Phenotype Reflects a Dysregulated and Expanded Epidermal Stem Cell Niche

Bohr, Stefan; Patel, Suraj J; Vasko, Radovan; Shen, Keyue; Huang, Guofeng; Yarmush, Martin Leon; Berthiaume, Francois
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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Hair cycling is a prime example of stem cell dependent tissue regeneration and replenishment, and its regulatory mechanisms remain poorly understood. In the present study, we evaluated the effect of a blockage in terminal keratinocytic lineage differentiation in the Foxn1(^{−/−}) nude phenotype on the epithelial progeny. Most notably we found a constitutive upregulation of LIM homeobox protein 2 (Lhx2), a marker gene of epithelial stem cellness indispensible for hair cycle progression. However, histological evidence along with an erratic, acyclic rise of otherwise suppressed CyclinD1 levels along with several key markers of keratinocyte lineage differentiation indicate a frustrated expansion of epithelial stem cell niches in skin. In addition, CD49f/CD34/CD200–based profiling demonstrated highly significant shifts in subpopulations of epithelial progeny. Intriguingly this appeared to include the expansion of Oct4+ stem cells in dermal fractions of skin isolates in the Foxn1 knock-out opposed to wild type. Overall our findings indicate that the Foxn1(^{−/−}) phenotype has a strong impact on epithelial progeny and thus offers a promising model to study maintenance and regulation of stem cell niches within skin not feasible in other in vitro or in vivo models.

Micro- and Nanoengineering Approaches to Control Stem Cell-Biomaterial Interactions

Dolatshahi-Pirouz, Alireza; Nikkhah, Mehdi; Kolind, Kristian; Dokmeci, Mehmet R.; Khademhosseini, Ali
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
EN_US
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As our population ages, there is a greater need for a suitable supply of engineered tissues to address a range of debilitating ailments. Stem cell based therapies are envisioned to meet this emerging need. Despite significant progress in controlling stem cell differentiation, it is still difficult to engineer human tissue constructs for transplantation. Recent advances in micro- and nanofabrication techniques have enabled the design of more biomimetic biomaterials that may be used to direct the fate of stem cells. These biomaterials could have a significant impact on the next generation of stem cell based therapies. Here, we highlight the recent progress made by micro- and nanoengineering techniques in the biomaterials field in the context of directing stem cell differentiation. Particular attention is given to the effect of surface topography, chemistry, mechanics and micro- and nanopatterns on the differentiation of embryonic, mesenchymal and neural stem cells.

Impurity of Stem Cell Graft by Murine Embryonic Fibroblasts – Implications for Cell-Based Therapy of the Central Nervous System

Molcanyi, Marek; Mehrjardi, Narges Zare; Schäfer, Ute; Haj-Yasein, Nadia Nabil; Brockmann, Michael; Penner, Marina; Riess, Peter; Reinshagen, Clemens; Rieger, Bernhard; Hannes, Tobias; Hescheler, Jürgen; Bosche, Bert
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
EN_US
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Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts – MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3 ± 2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies...

JAK/STAT-regulated Heterochromatin Formation in Drosophila Stem Cell Maintenance

Xing, Yalan ; Li, Willis X
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
ENG
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66.09%
Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Biomedical Genetics, 2010.; Stem cells are characterized by their ability to self-renew and to produce daughter cells that will initiate differentiation along a specific lineage. This property has long been attributed to the regulatory signals that stem cells receive from their microenvironments, which are commonly named ‘stem cell niches’. Previous studies have identified the Janus Kinase/Signal Transducer and Activators of Transcription (JAK/STAT) as a major niche signaling regulating germline stem cell (GSC) self-renewal in Drosophila melanogaster. However, the speculated STAT transcriptional targets in stem cells have not been revealed. My thesis investigates the mechanism of such regulation through modulating heterochromatin formation. The niche of Drosophila male germline stem cells is composed by a group of somatic cells called hub cells, which constitutively express cytokine-like ligand Unpaired (Upd). Upd activates JAK/STAT pathway in germline stem cells and somatic stem cells attached to the hub cells, specifying stem cell self-renewal. Without JAK/STAT signaling, GSCs are driven into differentiation other than self-proliferation...

Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts

Wada, N.; Wang, B.; Lin, N.H.; Laslett, A.; Gronthos, S.; Bartold, P.
Fonte: Blackwell Munksgaard Publicador: Blackwell Munksgaard
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
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Background and Objective: Human induced pluripotent stem (iPS) cells, which have similar properties to human embryonic stem (hES) cells, have been generated from neonatal and adult human dermal fibroblasts by reprogramming. iPS cells have high pluripotency and differentiation potential, and may be a potential autologous stem cell source for future regenerative therapy. Material and Methods: iPS cell lines from human gingival fibroblasts and, for the first time, from periodontal ligament fibroblasts, were generated by reprogramming using a retroviral transduction cocktail of OCT3/4, SOX2, KLF4 and c-MYC. iPS induction was investigated through expression of the embryonic stem cell markers SSEA4, OCT4, NANOG, GCTM-2, TG30 and TRA-1-60. Following in vitro differentiation, the expression of genes for differentiation markers for ectoderm (SOX1, PAX6), mesoderm [RUNX1, T(Brachyury)] and endoderm (GATA4, AFP) was assessed by real-time RT-PCR. The ability to form teratomas following implantation into mouse testes was assessed by histology. Results: Human gingival fibroblast- and periodontal ligament fibroblast-derived iPS cells showed similar characteristics to hES cells. Both sets of iPS cells displayed colony morphology comparable to that of hES cells and expressed the hES cell-associated cell-surface antigens...

Biomimetic three-dimensional microenvironment for controlling stem cell fate

Zhang, H.; Dai, S.; Bi, J.; Liu, K.K.
Fonte: The Royal Society Publishing Publicador: The Royal Society Publishing
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
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66.01%
Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the individual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.; Hu Zhang, Sheng Dai, Jingxiu Bi and Kuo-Kang Liu

Stem cell therapy for treatment of central nervous system pathology in α-mannosidosis guinea pigs.

Robinson, Aaron James
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2004
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66.04%
Lysosomal storage disorders (LSD) are a group of heritable genetic diseases resulting from a deficiency of one or more lysosomal enzpe activities, with broad pathological consequences. One of the most difficult aspects of these diseases to treat is central nervous system (CNS) pathology. Numerous strategies are being pursued in order to develop effective therapies for CNS pathology in LSD. One of these strategies involves the implantation of stem cells for the in vivo secretion of deficient enzyme in the brain, to be taken up by host cells, to therapeutic effect. α-Mannosidosis is a LSD resulting from a functional deficiency of lysosomal α-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, to cause progressive neurological degeneration and other somatic pathology. We have a guinea pig model of this disease that closely models human α-mannosidosis. Although enzyme replacement therapy has shown great promise for treatment of somatic pathology in α-mannosidosis guinea pigs, it is not effective for treatment of brain pathology. Thus, this disease model was chosen as an appropriate disorder for the evaluation of intra-cranial stem cell implantation as a therapeutic approach. α-Mannosidosis guinea pigs display significant neurological abnormalities as part of the course of their disease. We postulated that the development of tests to quantitate the loss of neurological function underlying these characteristics would be useful for evaluation of therapies in this model. The first aim of this study was thus to establish such tests. The Morris water maze has been used to evaluate therapies for neurological disease in mouse models of LSD...

Exploring the mesenchymal stem cell niche using high throughput screening

Ghaemi, S.; Harding, F.; Delalat, B.; Gronthos, S.; Voelcker, N.
Fonte: Elsevier Sci Ltd Publicador: Elsevier Sci Ltd
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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In the field of stem cell technology, future advancements rely on the effective isolation, scale-up and maintenance of specific stem cell populations and robust procedures for their directed differentiation. The stem cell microenvironment - or niche - encompasses signal inputs from stem cells, supporting cells and from the extracellular matrix. In this context, the contribution of physicochemical surface variables is being increasingly recognised. This paradigm can be exploited to exert control over cellular behaviour. However, the number of parameters at play, and their complex interactions, presents a formidable challenge in delineating how the decisions of cell fate are orchestrated within the niche. Additionally, in the case of mesenchymal stem cells (MSC), more than one type of stem cell niche has been identified. By employing high throughput screening (HTS) strategies, common and specific attributes of each MSC niche can be probed. Here, we explore biological, chemical and physical parameters that are known to influence MSC self-renewal and differentiation. We then review techniques and strategies that allow the HTS of surface properties for conditions that direct stem cell fate, using MSC as a case study. Finally, challenges in recapturing the niche...

Telomerbiologische Untersuchungen zum zellulären Umsatz hämatopoetischer Stammzellen nach haploidenter Transplantation mit hoher Dosis an Stammzellen; Telomere fluorescence measurements of cellular turnover of hematopoietic stem cells after haploidentical megadose stem cell transplantation

Wolke, Holger
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
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Telomere sind die Enden aller linearen eukaryotischer Chromosomen, welche aus repetitiven DNA-Sequenzen bestehen. Die Funktion der Telomere besteht im Schutz der Chromosomenenden vor Degradation, Fusion und Rekombination. In den meisten somatischen Zellen verkürzen sich die Telomere mit jedem Zellzyklus. Dieser Verlust an telomeren DNA-Sequenzen, bei allen Vertebraten T2AG3, kann als mitotische Uhr aufgefasst werden, mit der eine Zelle die Anzahl der Zellteilungen zählt und Lebensspanne und Zellalterung dirigiert. Messungen der Telomerlängen in peripheren Blutzellen mit kurzer Lebensdauer, wie zum Beispiel Granulozyten und Monozyten, können als Surrogatmarker für den Umsatz an hämatopoetischen Stammzellen während der physiologischen Hämatopoese, aber auch nach Stammzelltransplantation dienen. Frühere Studien konnten zeigten, dass das Verkürzen der Telomere auf das erste Jahr nach Transplantation beschränkt ist. Für die vorliegende Arbeit wurde eine Kombination aus quantitativer Fluoreszenz in situ Hybridisierung und Durchflußzytometrie, die sogenannte Flow-FISH Methode, verwendet, um Lymphozyten und myeloische Zellen von Empfängern und ihren jeweiligen Spendern nach allogen-haploidenter Megadose-Stammzelltransplantation zu analysieren. Es sollte auch untersucht werden...

Untersuchungen zur antikörper-abhängigen zellvermittelten antileukämischen Aktivität (ADCC) bei Kindern nach allogener Stammzelltransplantation; Investigations of antibody dependent cellular mediated cytotoxicity in children after allogenic stem cell transplantation

Stanojevic, Stanoje
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
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66.03%
Die Haupttodesursache nach allogener Stammzelltransplantation stellt das Rezidiv dar. Ursache hierfür ist das Persistieren von residuellen Leukämiezellen im Knochenmark, der sogenannten "Minimal Residual Disease" (MRD). Ziel immuntherapeutischer Ansätze ist es, derartige "Minimal Residual Disease"-Zellen nach allogener Stammzelltransplantation spezifisch zu eliminieren. Eine Möglichkeit um dieses Ziel zu erreichen, ist die Ausnutzung der antikörper-abhängigen zellvermittelten Zytotoxizität (ADCC). Im Rahmen der vorliegenden Dissertation wurde untersucht, ob Kinder, die allogen mit positiv-angereicherten CD34-positiven Stammzellen transplantiert worden sind, zur Ausübung der ADCC fähig sind. Dazu wurden mononukleäre Zellen aus dem peripheren Blut (PBMNC) allogen transplantierter Kinder isoliert und deren zytotoxische Fähigkeit beziehungsweise ADCC in vitro mittels des BATDA-Release-Assays überprüft. Für die ADCC wurde ein gegen das CD20 Antigen gerichteter chimärer Antikörper (Rituximab) verwendet. Außerdem wurde versucht, die ADCC mittels Interleukin-2 Stimulation (IL-2) zu steigern. In vitro konnte in der vorliegenden Arbeit gezeigt werden, daß 12 von 18 untersuchten Patienten (67 Prozent) in der Lage waren, ohne Interleukin-2 Aktivierung eine ADCC gegen die Tumorzellinien Raji oder MHH-CALL-4 auszuüben. Darüber hinaus wurden dann 94 Prozent der selben untersuchten Patienten durch Stimulation mit Interleukin-2 in die Lage versetzt...

Globalization of Stem Cell Science: An Examination of Current and Past Collaborative Research Networks

Luo, Jingyuan; Matthews, Kirstin R. W.
Fonte: Universidade Rice Publicador: Universidade Rice
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.04%
Science and engineering research has becoming an increasingly international phenomenon. Traditional bibliometric studies have not captured the evolution of collaborative partnerships between countries, particularly in emerging technologies such as stem cell science, in which an immense amount of investment has been made in the past decade. Analyzing over 2,800 articles from the top journals that include stem cell research in their publications, this study demonstrates the globalization of stem cell science. From 2000 to 2010, international collaborations increased from 20.9% to 36% of all stem cell publications analyzed. The United States remains the most prolific and the most dominant country in the field in terms of publications in high impact journals. But Asian countries, particularly China are steadily gaining ground. Exhibiting the largest relative growth, the percent of Chinese-authored stem cell papers grew more than ten-fold, while the percent of Chinese-authored international papers increased over seven times from 2000 to 2010. And while the percent of total stem cell publications exhibited modest growth for European countries, the percent of international publications increased more substantially, particularly in the United Kingdom. Overall...

The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information

Deregibus, Maria Chiara; Tetta, Ciro; Camussi, Giovanni
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
Relevância na Pesquisa
66.03%
It has been commonly supposed that adultstem cells co-localize with supporting cells withinspecific regions or specialized microenvironment in eachtissue/organ, called stem cell niche. This concept wasbased on the assumption that stem cells are intrinsicallyhierarchical in nature. However, recent data indicate thatstem cells may represent a continuum with reversiblealterations in phenotype taking place during the transitthrough cell cycle. Based on this dynamic interpretationit has been suggested that the so-called niche isrepresented by a single or only few cell types continuallyadjusting their phenotype and function to individualcircumstances. A critical component in the regulation ofthe continuum of stem cell phenotypes is themicroenvironment. In this context, microvesicles (MVs)account for the transfer of genetic information betweencells. Originally considered inert cellular debris, MVsare increasingly recognized to be important mediators ofcell-to-cell communication. MVs may transfer receptors,proteins, mRNA and microRNA to target cells viaspecific receptor-mediated interaction. In stem cellbiology the exchange of genetic information may bebidirectional from stromal to stem cells. In the context oftissue injury the MV-mediated transfer of geneticinformation may reprogram the phenotype of stem cellsto acquire features of the injured tissue cells. In addition...

Genetic dissection of a stem cell niche: the case of the Drosophila ovary

Bolívar, Jorge; Pearson, John; López-Onieva, Lourdes; González-Reyes, Acaimo
Fonte: John Wiley & Sons Publicador: John Wiley & Sons
Tipo: Artículo Formato: 21457 bytes; application/pdf
ENG
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11 páginas, 6 figuras, 2 tablas.-- El material suplementario referido en este artículo puede verse en www.interscience.wiley.com/jpages/1058-8388/suppmat; In this work, we demonstrate a powerful new tool for the manipulation of the stromal component of a well-established Drosophila stem cell niche. We have generated a bric-a-brac 1 (bab1)-Gal4 line that drives UAS expression in many somatic ovary cell types from early larval stages. Using this Gal4 line, we could effectively induce FLP/FRT-mediated recombination in the stromal cells of the ovarian germline stem cell niche. Mutant clones were observed in the developing ovary of larvae and pupae, including in somatic cell types that do not divide in the adult, such as the cap cells and the terminal filament cells. Exploiting the ability of bab1-Gal4 to generate large clones, we demonstrate that bab1-Gal4 is an effective tool for analyzing stem cell niche morphogenesis and cyst formation in the germarium. We have identified a novel requirement for engrailed in the correct organization of the terminal filaments. We also demonstrate an involvement for integrins in cyst formation and follicle cell encapsulation. Finally using bab1-Gal4 in conjunction with the Gal80 system, we show that while ectopic dpp expression from stromal cells is sufficient to induce hyperplastic stem cell growth...

Stem Cell-Based Strategies to Study, Prevent, and Treat Cartilage Injury and Osteoarthritis

Diekman, Brian O'Callaghan
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2012
Relevância na Pesquisa
66.01%

Articular cartilage is a smooth connective tissue that covers the ends of bones and protects joints from wear. Cartilage has a poor healing capacity, and the lack of treatment options motivates the development of tissue engineering strategies. The widespread cartilage degeneration associated with osteoarthritis (OA) is dramatically accelerated by joint injury, but the defined initiating event presents a therapeutic window for preventive treatments. In vitro model systems allow investigation of OA risk factors and screening of potential therapeutics. This dissertation develops stem-cell based strategies to 1) treat cartilage injury and OA using tissue-engineered cartilage, 2) prevent the development of OA by delivering stem cells to the joint after injury, and 3) study cartilage by establishing systems to model genetic and environmental contributors to OA.

Adipose-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (MSCs) are promising human adult cell sources for cartilage tissue engineering, but require distinct chondrogenic conditions. As compared to ASCs, MSCs demonstrated enhanced chondrogenesis in both alginate beads and cartilage-derived matrix scaffolds.

We hypothesized that MSC therapy would prevent post-traumatic arthritis (PTA) by altering the balance of inflammation and regeneration. Highly purified MSCs (CD45-TER119-PDGFRα+Sca-1+) rapidly expanded under hypoxic conditions. Unexpectedly...

The Attack of the Clones: Patent Law and Stem Cell Research

Rimmer, Matthew
Fonte: The Law Book Company Publicador: The Law Book Company
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
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This article considers the integral role played by patent law in respect of stem cell research. It highlights concerns about commercialization, access to essential medicines and bioethics. The article maintains that there is a fundamental ambiguity in the Patents Act 1990 (Cth) as to whether stem cell research is patentable subject matter. There is a need to revise the legislation in light of the establishment of the National Stem Cell Centre and the passing of the Research Involving Embryos Act 2002 (Cth). The article raises concerns about the strong patent protection secured by the Wisconsin Alumni Research Foundation and Geron Corporation in respect of stem cell research in the United States. It contends that a number of legal reforms could safeguard access to stem cell lines, and resulting drugs and therapies. Finally, this article explores how ethical concerns are addressed within the framework of the European Biotechnology Directive. It examines the decision of the European Patent Office in relation to the so-called "Edinburgh patent", and the inquiry of the European Group on Ethics in Science and New Technologies into "The Ethical Aspects of Patenting Involving Human Stem Cells".