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Sample records for model organism stem

  1. Advancing the flatworm Macrostomum lignano as a versatile model organism for stem cell research

    NARCIS (Netherlands)

    Demircan, T.D.

    2013-01-01

    Flatworms are a classical model for regeneration and stem cell research due to their astonishing regeneration capacity facilitated by pluripotent stem cells called neoblasts. M. lignano has several important experimental properties that make it a convenient model organism: the transparency of the

  2. The Flatworm Macrostomum lignano Is a Powerful Model Organism for Ion Channel and Stem Cell Research

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    Daniil Simanov

    2012-01-01

    Full Text Available Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. Here we introduce the flatworm Macrostomum lignano as a versatile model organism for addressing these topics. We discuss biological and experimental properties of M. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration in M. lignano.

  3. The Flatworm Macrostomum lignano Is a Powerful Model Organism for Ion Channel and Stem Cell Research.

    Science.gov (United States)

    Simanov, Daniil; Mellaart-Straver, Imre; Sormacheva, Irina; Berezikov, Eugene

    2012-01-01

    Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. Here we introduce the flatworm Macrostomum lignano as a versatile model organism for addressing these topics. We discuss biological and experimental properties of M. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration in M. lignano.

  4. Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

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    Martin Hoffmann

    Full Text Available Therapeutic application of mesenchymal stem cells (MSC requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

  5. Generation of functional organs from stem cells

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    Yunying Liu

    2013-01-01

    Full Text Available We are now well entering the exciting era of stem cells. Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, diabetes, and etc. It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue. In fact, organ transplantation has been successfully practiced in clinics for liver or kidney failure. However, the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs. Toward that direction, generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists. Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells, a blastocyst complementation system, tissue decellularization/recellularization and a combination of stem cells and tissue engineering.

  6. Integrated STEM Assessment Model

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    Bicer, Ali; Capraro, Robert M.; Capraro, Mary M.

    2017-01-01

    Previous research identified a strong correlation between mathematics and science performance albeit for small samples of students. Even though there was a high correlation between mathematics and science performance, researchers examining students' STEM achievement investigated mathematics and science achievement separately. The present study…

  7. Nucleosome Organization in Human Embryonic Stem Cells.

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    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  8. Comparative analysis of septic injury-inducible genes in phylogenetically distant model organisms of regeneration and stem cell research, the planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris

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    Vilcinskas Andreas

    2008-04-01

    Full Text Available Abstract Background The planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris have emerged as valuable model organisms in regeneration and stem cell research because of their prominent ability to regenerate a complete organism from any small body fragment. Under natural conditions wounding may result from predator attacks. These injuries open their innermost to a wide array of microbes present in the environment. Therefore, we established the hypothesis that regeneration processes may be linked to or at least accompanied by innate immune responses. In order to screen for septic wounding inducible genes we dissected individuals using a scalpel in the presence of a crude bacterial lipopolysaccharide preparation that is commonly used to elicit innate immune responses in animals and applied the suppression subtractive hybridization technique that selectively amplifies cDNAs of differentially expressed genes. Results This analysis revealed the induced expression of 27 genes in immune challenged Schmidtea and 35 genes in immune challenged Hydra. Identified genes from both animals encode proteins that share sequence similarities with potential homologues from other organisms known to be involved in signaling (e.g. calreticulin in Schmidtea and major vault protein in Hydra, stress responses (e.g. Hsp20 in Schmidtea and a PRP19/PSO4 DNA repair protein in Hydra, or to represent potential antimicrobial effectors (e.g. perforin-like protein in Schmidtea and PR-1-like protein and neutrophil cytosolic factor 1 in Hydra. As expected, septic wounding also induces expression of genes in Schmidtea and Hydra potentially involved in tissue remodeling associated with regeneration processes (e.g. matrix metalloproteinase in Schmidtea and a potential von Willebrand factor in Hydra. Conclusion We identified numerous immune-inducible genes in Hydra and Schmidtea that show a similar distribution corresponding to their physiological roles, although lineages of

  9. The role of adipose-derived stem cells in a self-organizing 3D model with regard to human soft tissue healing.

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    Oberringer, Martin; Bubel, Monika; Jennewein, Martina; Guthörl, Silke; Morsch, Tamara; Bachmann, Sophie; Metzger, Wolfgang; Pohlemann, Tim

    2018-01-05

    The clinical phenomenon of inadequate soft tissue healing still remains an important issue. The occurrence of chronic wounds is correlated to the life span, which is still increasing in western countries. Tissue engineering products containing adipose-derived stem cells are discussed as a promising therapeutic approach. Several studies confirmed the value of these cells for soft tissue healing improvement, suggesting a paracrine as well as a direct effect on vessel repair and angiogenesis. In an attempt to figure out specific effects of adipose-derived stem cells on dermal microvascular endothelial cells with respect to the different phases of soft tissue healing, we designed a 3D in vitro model on the basis of spheroids. Basic parameters like spheroid volume, cell numbers, and rate of apoptotic cells were determined in dependence on culture time, on different oxygen conditions and using mono- as well as co-cultures of both cell types. Furthermore we focused on gene expression and protein levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor, which are discussed against the background of therapies for chronic wounds. The visualization of α-smooth muscle actin allowed the estimation of the function of adipose-derived stem cells as stabilizer for dermal microvascular endothelial cells. The results of the present 3D model underscore a paracrine effect of adipose-derived stem cells on microvessel repair during early hypoxic conditions, whereas a stabilizing effect occurs during a later phase of soft tissue healing, simultaneously to reoxygenation.

  10. Mathematical Modeling: A Bridge to STEM Education

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    Kertil, Mahmut; Gurel, Cem

    2016-01-01

    The purpose of this study is making a theoretical discussion on the relationship between mathematical modeling and integrated STEM education. First of all, STEM education perspective and the construct of mathematical modeling in mathematics education is introduced. A review of literature is provided on how mathematical modeling literature may…

  11. Empowering Effective STEM Role Models to Promote STEM Equity in Local Communities

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    Harte, T.; Taylor, J.

    2017-12-01

    Empowering Effective STEM Role Models, a three-hour training developed and successfully implemented by NASA Langley Research Center's Science Directorate, is an effort to encourage STEM professionals to serve as role models within their community. The training is designed to help participants reflect on their identity as a role model and provide research-based strategies to effectively engage youth, particularly girls, in STEM (science, technology, engineering, and mathematics). Research shows that even though girls and boys do not demonstrate a significant difference in their ability to be successful in mathematics and science, there is a significant difference in their confidence level when participating in STEM subject matter and pursuing STEM careers. The Langley training model prepares professionals to disrupt this pattern and take on the habits and skills of effective role models. The training model is based on other successful models and resources for role modeling in STEM including SciGirls; the National Girls Collaborative; and publications by the American Association of University Women and the National Academies. It includes a significant reflection component, and participants walk through situation-based scenarios to practice a focused suite of research-based strategies. These strategies can be implemented in a variety of situations and adapted to the needs of groups that are underrepresented in STEM fields. Underpinning the training and the discussions is the fostering of a growth mindset and promoting perseverance. "The Power of Yet" becomes a means whereby role models encourage students to believe in themselves, working toward reaching their goals and dreams in the area of STEM. To provide additional support, NASA Langley role model trainers are available to work with a champion at other organizations to facilitate the training. This champion helps recruit participants, seeks leadership buy-in, and helps provide valuable insights for needs and

  12. Genome engineering of stem cell organoids for disease modeling

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    Yingmin Sun

    2017-01-01

    Full Text Available Abstract Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.

  13. A MODEL FOR POSTRADIATION STEM CELL KINETICS,

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    In polycythemic rats observed for 17 days postradiation (300 R, 250 KVP X-rays) it was noted that stem cell release diminished to 8 percent of the...correlate these findings with a kinetic model of erythropoiesis. It was suggested that the initial depression in stem cell release might be due to cellular

  14. Human pluripotent stem cells: an emerging model in developmental biology.

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    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

  15. Queer in STEM Organizations: Workplace Disadvantages for LGBT Employees in STEM Related Federal Agencies

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    Erin A. Cech

    2017-02-01

    Full Text Available Lesbian, gay, bisexual, and transgender (LGBT individuals in U.S. workplaces often face disadvantages in pay, promotion, and inclusion and emergent research suggests that these disadvantages may be particularly pernicious within science and engineering environments. However, no research has systematically examined whether LGBT employees indeed encounter disadvantages in science, technology, engineering and math (STEM organizations. Using representative data of over 30,000 workers employed in six STEM-related federal agencies (the Department of Energy, the Environmental Protection Agency, the National Science Foundation, NASA, the Nuclear Regulatory Commission, and the Department of Transportation, over 1000 of whom identify as LGBT, we compare the workplace experiences of LGBT employees in STEM-related federal agencies with those of their non-LGBT colleagues. Across numerous measures along two separate dimensions of workplace experiences—perceived treatment as employees and work satisfaction—LGBT employees in STEM agencies report systematically more negative workplace experiences than their non-LGBT colleagues. Exploring how these disadvantages vary by agency, supervisory status, age cohort, and gender, we find that LGBT persons have more positive experiences in regulatory agencies but that supervisory status does not improve LGBT persons’ experiences, nor do the youngest LGBT employees fare better than their older LGBT colleagues. LGBT-identifying men and women report similar workplace disadvantages. We discuss the implications of these findings for STEM organizations and STEM inequality more broadly.

  16. The Stem Cell Club: a model for unrelated stem cell donor recruitment.

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    Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

    2017-12-01

    Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

  17. Local stem cell depletion model for radiation myelitis

    International Nuclear Information System (INIS)

    Yaes, R.J.; Kalend, A.

    1988-01-01

    We propose a model for normal tissue damage based on the assumption that adult mammalian stem cells have limited mobility and, consequently, for each organ, there is a maximum volume (the critical volume, Vc), that can be repopulated and repaired by a single surviving stem cell. This concept is applied to a simple, 1-dimensional model of the spinal cord, where the critical volume is a slice of thickness, t, assumed to be small compared to lengths of spinal cord usually irradiated clinically. The probability of myelitis is explicitly obtained as a function of the dose, dose per fraction, length of cord irradiated, slice thickness, number of stem cells per slice and parameters alpha and beta of the stem cell survival curve. The complication probability is expressed as a triple negative exponential function of dose analogous to the double negative exponential function for tumor control, resulting in a steep dose-response curve with short tails in both the high dose and low dose regions. We show that the model predictions are compatible with the experimental data for radiation myelitis in the rat. We discuss how this concept can be applied to other organs such as skin and to organs composed of structurally and functionally distinct subunits, such as the kidney

  18. Genome organization, instabilities, stem cells, and cancer

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    Senthil Kumar Pazhanisamy

    2009-01-01

    Full Text Available It is now widely recognized that advances in exploring genome organization provide remarkable insights on the induction and progression of chromosome abnormalities. Much of what we know about how mutations evolve and consequently transform into genome instabilities has been characterized in the spatial organization context of chromatin. Nevertheless, many underlying concepts of impact of the chromatin organization on perpetuation of multiple mutations and on propagation of chromosomal aberrations remain to be investigated in detail. Genesis of genome instabilities from accumulation of multiple mutations that drive tumorigenesis is increasingly becoming a focal theme in cancer studies. This review focuses on structural alterations evolve to raise a variety of genome instabilities that are manifested at the nucleotide, gene or sub-chromosomal, and whole chromosome level of genome. Here we explore an underlying connection between genome instability and cancer in the light of genome architecture. This review is limited to studies directed towards spatial organizational aspects of origin and propagation of aberrations into genetically unstable tumors.

  19. Large animal models for stem cell therapy.

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    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  20. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  1. The Effect of STEM Learning through the Project of Designing Boat Model toward Student STEM Literacy

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    Tati, T.; Firman, H.; Riandi, R.

    2017-09-01

    STEM Learning focusses on development of STEM-literate society, the research about implementation of STEM learning to develope students’ STEM literacy is still limited. This study is aimed to examine the effect of implementation STEM learning through the project of designing boat model on students STEM literacy in energy topic. The method of this study was a quasi-experiment with non-randomized pretest-posttest control group design. There were two classes involved, the experiment class used Project Based Learning with STEM approach and control class used Project-Based Learning without STEM approach. A STEM Literacy test instrument was developed to measure students STEM literacy which consists of science literacy, mathematics literacy, and technology-engineering literacy. The analysis showed that there were significant differences on improvement science literacy, mathematics technology-engineering between experiment class and control class with effect size more than 0.8 (large effect). The difference of improvement of STEM literacy between experiment class and control class is caused by the existence of design engineering activity which required students to apply the knowledge from every field of STEM. The challenge that was faced in STEM learning through design engineering activity was how to give the students practice to integrate STEM field in solving the problems. In additional, most of the students gave positive response toward implementation of STEM learning through design boat model project.

  2. Desensitization for solid organ and hematopoietic stem cell transplantation

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    Zachary, Andrea A; Leffell, Mary S

    2014-01-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. PMID:24517434

  3. [A medical-pharmaceutical partnership model as a contributor to the success in conditioning regimen for allogenic hematopoietic stem cell transplantation in adults: a cross-reflection on our organizations].

    Science.gov (United States)

    Bourget, Philippe; Falaschi, Ludivine; Suarez, Felipe; Galland, Valérie; Blot, Dominique; Trompette, Caroline; Sibon, David; Fontbrune, Flore Sicre de; Merlette, Christophe; Vidal, Fabrice; Corriol, Odile; Giraud, Bérénice; Broissand, Christine; Clement, Rozenn; Hermine, Olivier

    2012-06-01

    Allogeneic hematopoietic stem-cell transplant (allo-SCT) remains the only cure for many hematological malignancies and some benign and congenital diseases. Busulfan, proposed in its injectable form, has quickly become a mainstay of pharmacological and myeloablative (or non-myeloablative) conditioning. This is following the outbreak in 2010 of a multicenter international clinical phase II trial, we tested the robustness and reliability of our organization in a complex model of organization and multifactorial partnership. In this type "BuCy2" protocol based on a classical treatment duration of 4 consecutive days, the administration of IV busulfan is given in one single daily infusion instead of the conventional 16 infusions, while keeping the same total dose. Under these conditions, the treatment is totally secured using a therapeutic drug monitoring of busulfan, applied in real-time. The process is technically complex and requires the very close cooperation of the teams involved. A strength, weakness, opportunity and threat (SWOT) analysis has been constructed; it fully supports continuous quality improvement to the triple benefit of the nursing chain, the patients and their environment. Several critical points were identified and corrected. The experiment strongly contributes to the safety and security of the medication circuit at the hospital and, improves the performance of allo-SCT. It also contributes to the protection of all actors in the health field and their working environment via a well-functioning quality management system.

  4. Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats

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    Michelle Cruz

    2012-01-01

    Full Text Available The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days later pelvic organs and muscles were imaged for visualization of GFP-positive cells. Significantly more MSCs home to the urethra, vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs were present 10 days after injection but GFP intensity had decreased. This study provides basic science evidence that intravenous administration of MSCs could provide an effective route for cell-based therapy to facilitate repair after injury and treat stress incontinence.

  5. Modeling Keratoconus Using Induced Pluripotent Stem Cells.

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    Joseph, Roy; Srivastava, Om P; Pfister, Roswell R

    2016-07-01

    To model keratoconus (KC) using induced pluripotent stem cells (iPSC) generated from fibroblasts of both KC and normal human corneal stroma by a viral method. Both normal and KC corneal fibroblasts from four human donors were reprogramed directly by delivering reprogramming factors in a single virus using 2A "self-cleaving" peptides, using a single polycistronic lentiviral vector coexpressing four transcription factors (Oct 4, Sox2, Klf4, and Myc) to yield iPSC. These iPS cells were characterized by immunofluorescence detection using of stem cell markers (SSEA4, Oct4, and Sox2). The mRNA sequencing was performed and the datasets were analyzed using ingenuity pathways analysis (IPA) software. The generated stem cell-like clones expressed the pluripotency markers, SSEA4, Oct4, Sox2, Tra-1-60, and also expressed pax6. Our transcriptome analysis showed 4300 genes, which had 2-fold change and 870 genes with a q-value of iPSC compared to normal iPSC. One of the genes that showed difference in KC iPSC was FGFR2 (down-regulated by 2.4 fold), an upstream target of Pi3-Kinase pathway, was further validated in keratoconus corneal sections and also KC iPSC-derived keratocytes (down regulated by 2.0-fold). Both normal and KC-derived keratocytes expressed keratocan, signature marker for keratocytes. KC iPSC-derived keratocytes showed adverse growth and proliferation and was further confirmed by using Ly2924002, a PI3k inhibitor, which severely affected the growth and differentiation in normal iPSC. Based on our result, we propose a model for KC in which inhibition FGFR2-Pi3-Kinase pathway affects the AKT phosphorylation, and thus affecting the keratocytes survival signals. This inhibition of the survival signals could be a potential mechanism for the KC-specific decreased cell survival and apoptosis of keratocytes.

  6. Organization of haemopoietic stem cells: the generation-age hypothesis

    International Nuclear Information System (INIS)

    Rosendaal, M.; Hodgson, G.S.; Bradley, T.R.

    1978-01-01

    This paper proposes that the previous division history of each stem cell is one determinant of the functional organisation of the haemopoietic stem cell population. Older stem cell are used to form blood before younger ones. The stem cells generating capacity of a lineage is finite, and cells are eventually lost to the system by forming two committed precursors of the cell lines, and the next oldest stem cell takes over. Hence the proposed term 'generation-age hypothesis', supported by experimental evidence. Older stem cells from normal bone marrow and 13 day foetal liver were stripped away with phase-specific drugs revealing a younger population of stem cells with three-to four-fold greater stem cell generating capacity. Normal stem cells aged by continuous irradiation and serial retransplantation had eight-fold reduced generating capacity. That of stem cells in the bloodstream was half to a quarter that of normal bone marrow stem cells. There were some circulating stem cells, identified by reaction to brain-associated antigen, positive for 75% of normal femoral stem cells but not their progeny, whose capacity for stem cell generation was an eighth to one fortieth that of normal cells. (U.K.)

  7. Conditioning a segmented stem profile model for two diameter measurements

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    Raymond L. Czaplewski; Joe P. Mcclure

    1988-01-01

    The stem profile model of Max and Burkhart (1976) is conditioned for dbh and a second upper stem measurement. This model was applied to a loblolly pine data set using diameter outside bark at 5.3m (i.e., height of 17.3 foot Girard form class) as the second upper stem measurement, and then compared to the original, unconditioned model. Variance of residuals was reduced...

  8. Repopulation of decellularized whole organ scaffold using stem cells: an emerging technology for the development of neo-organ.

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    Khan, Aleem Ahmed; Vishwakarma, Sandeep Kumar; Bardia, Avinash; Venkateshwarulu, J

    2014-12-01

    Demand of donor organs for transplantation in treatment of organ failure is increasing. Hence there is a need to develop new strategies for the alternative sources of organ development. Attempts are being made to use xenogenic organs by genetic manipulation but the organ rejection against human always has been a major challenge for the survival of the graft. Advancement in the genetic bioengineering and combination of different allied sciences for the development of humanized organ system, the therapeutic influence of stem cell fraction on the reconstitution of organ architecture and their regenerative abilities in different tissues and organs provides a better approach to solve the problem of organ shortage. However, the available strategies for generating the organ/tissue scaffolds limit its application due to the absence of complete three-dimensional (3D) organ architecture, mechanical strength, long-term cell survival, and vascularization. Repopulation of whole decellularized organ scaffolds using stem cells has added a new dimension for creating new bioengineered organs. In recent years, several studies have demonstrated the potential application of decellularization and recellularization approach for the development of functional bio-artificial organs. With the help of established procedures for conditioning, extensive stem cells and organ engineering experiments/transplants for the development of humanized organs will allow its preclinical evaluation for organ regeneration before translation to the clinic. This review focuses on the major aspects of organ scaffold generation and repopulation of different types of whole decellularized organ scaffolds using stem cells for the functional benefit and their confines.

  9. Growth models for tree stems and vines

    Science.gov (United States)

    Bressan, Alberto; Palladino, Michele; Shen, Wen

    2017-08-01

    The paper introduces a PDE model for the growth of a tree stem or a vine. The equations describe the elongation due to cell growth, and the response to gravity and to external obstacles. An additional term accounts for the tendency of a vine to curl around branches of other plants. When obstacles are present, the model takes the form of a differential inclusion with state constraints. At each time t, a cone of admissible reactions is determined by the minimization of an elastic deformation energy. The main theorem shows that local solutions exist and can be prolonged globally in time, except when a specific ;breakdown configuration; is reached. Approximate solutions are constructed by an operator-splitting technique. Some numerical simulations are provided at the end of the paper.

  10. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    Science.gov (United States)

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  11. Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme.

    Science.gov (United States)

    Sneddon, Julie B; Borowiak, Malgorzata; Melton, Douglas A

    2012-11-29

    One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types, but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process. Using the pancreatic lineage as a model for embryonic-stem-cell differentiation, we demonstrate that this is a solvable problem. Co-culture with organ-matched mesenchyme permits proliferation and self-renewal of progenitors, without differentiation, and enables an expansion of more than a million-fold for human endodermal cells with full retention of their developmental potential. This effect is specific both to the mesenchymal cell and to the progenitor being amplified. Progenitors that have been serially expanded on mesenchyme give rise to glucose-sensing, insulin-secreting cells when transplanted in vivo. Theoretically, the identification of stage-specific renewal signals can be incorporated into any scheme for the efficient production of large numbers of differentiated cells from stem cells and may therefore have wide application in regenerative biology.

  12. Total tree, merchantable stem and branch volume models for ...

    African Journals Online (AJOL)

    Total tree, merchantable stem and branch volume models for miombo woodlands of Malawi. Daud J Kachamba, Tron Eid. Abstract. The objective of this study was to develop general (multispecies) models for prediction of total tree, merchantable stem and branch volume including options with diameter at breast height (dbh) ...

  13. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction

    International Nuclear Information System (INIS)

    Francois, S.

    2006-01-01

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

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

    Directory of Open Access Journals (Sweden)

    Min Su Kim

    2008-03-01

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

  15. The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration

    Directory of Open Access Journals (Sweden)

    Luca Gentile

    2011-01-01

    Full Text Available Planarian flatworms are an exception among bilaterians in that they possess a large pool of adult stem cells that enables them to promptly regenerate any part of their body, including the brain. Although known for two centuries for their remarkable regenerative capabilities, planarians have only recently emerged as an attractive model for studying regeneration and stem cell biology. This revival is due in part to the availability of a sequenced genome and the development of new technologies, such as RNA interference and next-generation sequencing, which facilitate studies of planarian regeneration at the molecular level. Here, we highlight why planarians are an exciting tool in the study of regeneration and its underlying stem cell biology in vivo, and discuss the potential promises and current limitations of this model organism for stem cell research and regenerative medicine.

  16. Integration of embryonic stem cells in metanephric kidney organ culture.

    Science.gov (United States)

    Steenhard, Brooke M; Isom, Kathryn S; Cazcarro, Patricia; Dunmore, Judy H; Godwin, Alan R; St John, Patricia L; Abrahamson, Dale R

    2005-06-01

    Many stages of nephrogenesis can be studied using cultured embryonic kidneys, but there is no efficient technique available to readily knockdown or overexpress transgenes for rapid evaluation of resulting phenotypes. Embryonic stem (ES) cells have unlimited developmental potential and can be manipulated at the molecular genetic level by a variety of methods. The aim of this study was to determine if ES cells could respond to developmental signals within the mouse embryonic day 12 to embryonic day 13 (E12 to E13) kidney microenvironment and incorporate into kidney structures. ROSA26 ES cells were shown to express beta-galactosidase ubiquitously when cultured in the presence of leukemia inhibitory factor to suppress differentiation. When these cells were microinjected into E12 to E13 metanephroi and then placed in transwell organ culture, ES cell-derived, beta-galactosidase-positive cells were identified in epithelial structures resembling tubules. On rare occasions, individual ES cells were observed in structures resembling glomerular tufts. Electron microscopy showed that the ES cell-derived tubules were surrounded by basement membrane and had apical microvilli and junctional complexes. Marker analysis revealed that a subset of these epithelial tubules bound Lotus tetragonolobus and expressed alpha(1) Na(+)/K(+) ATPase. ES cells were infected before injection with a cytomegalovirus promoter-green fluorescence protein (GFP) adenovirus and GFP expression was found as early as 18 h, persisting for up to 48 h in cultured kidneys. This ES cell technology may achieve the objective of obtaining a versatile cell culture system in which molecular interventions can be used in vitro and consequences of these perturbations on the normal kidney development program in vivo can be studied.

  17. FireStem2D — A two-dimensional heat transfer model for simulating tree stem injury in fires

    Science.gov (United States)

    Efthalia K. Chatziefstratiou; Gil Bohrer; Anthony S. Bova; Ravishankar Subramanian; Renato P.M. Frasson; Amy Scherzer; Bret W. Butler; Matthew B. Dickinson

    2013-01-01

    FireStem2D, a software tool for predicting tree stem heating and injury in forest fires, is a physically-based, two-dimensional model of stem thermodynamics that results from heating at the bark surface. It builds on an earlier one-dimensional model (FireStem) and provides improved capabilities for predicting fire-induced mortality and injury before a fire occurs by...

  18. Mesenchymal Stem Cells in Sepsis and Associated Organ Dysfunction: A Promising Future or Blind Alley?

    Directory of Open Access Journals (Sweden)

    Jan Horák

    2017-01-01

    Full Text Available Sepsis, newly defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is the most common cause of death in ICUs and one of the principal causes of death worldwide. Although substantial progress has been made in the understanding of fundamental mechanisms of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm “one disease, one drug” is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. In this context, the immune-reprogramming properties of cell-based therapy using mesenchymal stem cells (MSC represent an emerging therapeutic strategy in sepsis and associated organ dysfunction. This article provides an update of the current knowledge regarding MSC in preclinical models of sepsis and sepsis-induced acute kidney injury. Recommendations for further translational research in this field are discussed.

  19. Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip.

    Science.gov (United States)

    Zhang, Jie; Wei, Xiaofeng; Zeng, Rui; Xu, Feng; Li, XiuJun

    2017-06-01

    Microfluidic lab-on-a-chip provides a new platform with unique advantages to mimic complex physiological microenvironments in vivo and has been increasingly exploited to stem cell research. In this review, we highlight recent advances of microfluidic devices for stem cell culture and differentiation toward the development of organ-on-a-chip, especially with an emphasis on vital innovations within the last 2 years. Various aspects for improving on-chip stem-cell culture and differentiation, particularly toward organ-on-a-chip, are discussed, along with microenvironment control, surface modification, extracellular scaffolds, high throughput and stimuli. The combination of microfluidic technologies and stem cells hold great potential toward versatile systems of 'organ-on-a-chip' as desired. Adapted with permission from [1-8].

  20. Nuclear organization during in vitro differentiation of porcine mesenchymal stem cells (MSCs) into adipocytes.

    Science.gov (United States)

    Stachecka, Joanna; Walczak, Agnieszka; Kociucka, Beata; Ruszczycki, Błażej; Wilczyński, Grzegorz; Szczerbal, Izabela

    2018-02-01

    Differentiation of progenitor cells into adipocytes is accompanied by remarkable changes in cell morphology, cytoskeletal organization, and gene expression profile. Mature adipocytes are filled with a large lipid droplet and the nucleus tends to move to the cell periphery. It was hypothesized that the differentiation process is also associated with changes of nuclear organization. The aim of this study was to determine the number and distribution of selected components of nuclear architecture during porcine in vitro adipogenesis. The pig is an important animal model sharing many similarities to humans at the anatomical, physiological, and genetic levels and has been recognized as a good model for human obesity. Thus, understanding how cellular structures important for fundamental nuclear processes may be altered during adipocyte differentiation is of great importance. Mesenchymal stem cells (MSCs) were derived from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) and were cultured for 7 days in the adipogenic medium. A variable differentiation potential of these cell populations towards adipogenic lineage was observed, and for further study, a comparative characteristic of the nuclear organization in BM-MSCs and AD-MSCs was performed. Nuclear substructures were visualized by indirect immunofluorescence (nucleoli, nuclear speckles, PML bodies, lamins, and HP1α) or fluorescence in situ hybridization (telomeres) on fixed cells at 0, 3, 5, and 7 days of differentiation. Comprehensive characterization of these structures, in terms of their number, size, dynamics, and arrangement in three-dimensional space of the nucleus, was performed. It was found that during differentiation of porcine MSCs into adipocytes, changes of nuclear organization occurred and concerned: (1) the nuclear size and shape; (2) reduced lamin A/C expression; and (3) reorganization of chromocenters. Other elements of nuclear architecture such as nucleoli, SC-35 nuclear speckles, and telomeres

  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. Stem cells in animal asthma models: a systematic review.

    Science.gov (United States)

    Srour, Nadim; Thébaud, Bernard

    2014-12-01

    Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  3. Engineering three-dimensional stem cell morphogenesis for the development of tissue models and scalable regenerative therapeutics.

    Science.gov (United States)

    Kinney, Melissa A; Hookway, Tracy A; Wang, Yun; McDevitt, Todd C

    2014-02-01

    The physiochemical stem cell microenvironment regulates the delicate balance between self-renewal and differentiation. The three-dimensional assembly of stem cells facilitates cellular interactions that promote morphogenesis, analogous to the multicellular, heterotypic tissue organization that accompanies embryogenesis. Therefore, expansion and differentiation of stem cells as multicellular aggregates provides a controlled platform for studying the biological and engineering principles underlying spatiotemporal morphogenesis and tissue patterning. Moreover, three-dimensional stem cell cultures are amenable to translational screening applications and therapies, which underscores the broad utility of scalable suspension cultures across laboratory and clinical scales. In this review, we discuss stem cell morphogenesis in the context of fundamental biophysical principles, including the three-dimensional modulation of adhesions, mechanics, and molecular transport and highlight the opportunities to employ stem cell spheroids for tissue modeling, bioprocessing, and regenerative therapies.

  4. Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

    Science.gov (United States)

    Hoffman, Andrew M; Dow, Steven W

    2016-07-01

    Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. © 2016 AlphaMed Press.

  5. Input point distribution for regular stem form spline modeling

    Directory of Open Access Journals (Sweden)

    Karel Kuželka

    2015-04-01

    Full Text Available Aim of study: To optimize an interpolation method and distribution of measured diameters to represent regular stem form of coniferous trees using a set of discrete points. Area of study: Central-Bohemian highlands, Czech Republic; a region that represents average stand conditions of production forests of Norway spruce (Picea abies [L.] Karst. in central Europe Material and methods: The accuracy of stem curves modeled using natural cubic splines from a set of measured diameters was evaluated for 85 closely measured stems of Norway spruce using five statistical indicators and compared to the accuracy of three additional models based on different spline types selected for their ability to represent stem curves. The optimal positions to measure diameters were identified using an aggregate objective function approach. Main results: The optimal positions of the input points vary depending on the properties of each spline type. If the optimal input points for each spline are used, then all spline types are able to give reasonable results with higher numbers of input points. The commonly used natural cubic spline was outperformed by other spline types. The lowest errors occur by interpolating the points using the Catmull-Rom spline, which gives accurate and unbiased volume estimates, even with only five input points. Research highlights: The study contributes to more accurate representation of stem form and therefore more accurate estimation of stem volume using data obtained from terrestrial imagery or other close-range remote sensing methods.

  6. Induced pluripotent stem cells and Parkinson's disease: modelling and treatment.

    Science.gov (United States)

    Xu, Xiaoyun; Huang, Jinsha; Li, Jie; Liu, Ling; Han, Chao; Shen, Yan; Zhang, Guoxin; Jiang, Haiyang; Lin, Zhicheng; Xiong, Nian; Wang, Tao

    2016-02-01

    Many neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hiPSCs, as well as the potential value of hiPSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment. © 2016 John Wiley & Sons Ltd.

  7. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Science.gov (United States)

    Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

    2016-01-01

    Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  8. Merging concepts - coupling an agent-based model of hematopoietic stem cells with an ODE model of granulopoiesis.

    Science.gov (United States)

    Krinner, Axel; Roeder, Ingo; Loeffler, Markus; Scholz, Markus

    2013-11-01

    Hematopoiesis is a complex process involving different cell types and feedback mechanisms mediated by cytokines. This complexity stimulated various models with different scopes and applications. A combination of complementary models promises to provide their mutual confirmation and to explain a broader range of scenarios. Here we propose a combination of an ordinary differential equation (ODE) model of human granulopoiesis and an agent-based model (ABM) of hematopoietic stem cell (HSC) organization. The first describes the dynamics of bone marrow cell stages and circulating cells under various perturbations such as G-CSF treatment or chemotherapy. In contrast to the ODE model describing cell numbers, our ABM focuses on the organization of individual cells in the stem population. We combined the two models by replacing the HSC compartment of the ODE model by a difference equation formulation of the ABM. In this hybrid model, regulatory mechanisms and parameters of the original models were kept unchanged except for a few specific improvements: (i) Effect of chemotherapy was restricted to proliferating HSC and (ii) HSC regulation in the ODE model was replaced by the intrinsic regulation of the ABM. Model simulations of bleeding, chronic irradiation and stem cell transplantation revealed that the dynamics of hybrid and ODE model differ markedly in scenarios with stem cell damage. Despite these differences in response to stem cell damage, both models explain clinical data of leukocyte dynamics under four chemotherapy regimens. ABM and ODE model proved to be compatible and were combined without altering the structure of both models. The new hybrid model introduces model improvements by considering the proliferative state of stem cells and enabling a cell cycle-dependent effect of chemotherapy. We demonstrated that it is able to explain and predict granulopoietic dynamics for a large variety of scenarios such as irradiation, bone marrow transplantation, chemotherapy and

  9. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... some of the phenotype can be observed in-vitro, but these phenotypes, when compared to the patient, correlate extremely well. Many studies have found novel molecular mechanisms involved in the disease and therefore elucidate new potential targets for reversing the phenotype. Future research...

  10. Modeling the Chagas’ disease after stem cell transplantation

    Science.gov (United States)

    Galvão, Viviane; Miranda, José Garcia Vivas

    2009-04-01

    A recent model for Chagas’ disease after stem cell transplantation is extended for a three-dimensional multi-agent-based model. The computational model includes six different types of autonomous agents: inflammatory cell, fibrosis, cardiomyocyte, proinflammatory cytokine tumor necrosis factor- α, Trypanosoma cruzi, and bone marrow stem cell. Only fibrosis is fixed and the other types of agents can move randomly through the empty spaces using the three-dimensional Moore neighborhood. Bone marrow stem cells can promote apoptosis in inflammatory cells, fibrosis regression and can differentiate in cardiomyocyte. T. cruzi can increase the number of inflammatory cells. Inflammatory cells and tumor necrosis factor- α can increase the quantity of fibrosis. Our results were compared with experimental data giving a fairly fit and they suggest that the inflammatory cells are important for the development of fibrosis.

  11. Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges.

    Science.gov (United States)

    Kerkis, Irina; Haddad, Monica Santoro; Valverde, Cristiane Wenceslau; Glosman, Sabina

    2015-12-14

    Huntington's disease (HD) is an inherited disease that causes progressive nerve cell degeneration. It is triggered by a mutation in the HTT gene that strongly influences functional abilities and usually results in movement, cognitive and psychiatric disorders. HD is incurable, although treatments are available to help manage symptoms and to delay the physical, mental and behavioral declines associated with the condition. Stem cells are the essential building blocks of life, and play a crucial role in the genesis and development of all higher organisms. Ablative surgical procedures and fetal tissue cell transplantation, which are still experimental, demonstrate low rates of recovery in HD patients. Due to neuronal cell death caused by accumulation of the mutated huntingtin (mHTT) protein, it is unlikely that such brain damage can be treated solely by drug-based therapies. Stem cell-based therapies are important in order to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. This review summarizes current knowledge on neural stem/progenitor cell and mesenchymal stem cell transplantation, which has been carried out in several animal models of HD, discussing cell distribution, survival and differentiation after transplantation, as well as functional recovery and anatomic improvements associated with these approaches. We also discuss the usefulness of this information for future preclinical and clinical studies in HD.

  12. Adult Stem Cell-Derived Kidney Organoids to Model Tissue Physiology and Disease

    NARCIS (Netherlands)

    Schutgens, Frans

    2017-01-01

    “Organoid” is defined as a 3D structure grown from stem cells and consisting of organ-specific cell types that self-organizes through cell sorting and spatially restricted lineage commitment. Organoids can be derived from either adult stem cells (ASCs) or pluripotent stem cells (PSCs). The

  13. COMPARISON OF HUMAN ADIPOSE-DERIVED STEM CELLS AND BONE MARROW-DERIVED STEM CELLS IN A MYOCARDIAL INFARCTION MODEL

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Holst-Hansen, Claus

    2012-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... randomised to receive intramyocardial injections of adipose-derived stem cells, bone marrow derived mesenchymal stem cells or phosphate-buffered saline one week following induction of myocardial infarction. Results: After four weeks, left ventricular ejection fraction was improved in the adipose-derived stem...

  14. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

    Science.gov (United States)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

    2017-04-01

    Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  15. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche.

    Science.gov (United States)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R; Gumucio, Deborah L; Fu, Jianping

    2017-04-01

    Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  16. Skeletal muscle regeneration models for experimental stem cell therapy

    Czech Academy of Sciences Publication Activity Database

    Čížková, D.; Mokrý, J.; Soukup, Tomáš

    2006-01-01

    Roč. 8, č. S2 (2006), s. 64-65 ISSN 1465-3249. [International Conference "Strategies in Tissue Engineering" /2./. 31.05.2006-02.06.2006, Würzburg] Keywords : rat * skeletal muscle * stem cell s * muscle regeneration * muscle regeneration model Subject RIV: ED - Physiology

  17. Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

    NARCIS (Netherlands)

    Tüysüz, Nesrin; van Bloois, Louis|info:eu-repo/dai/nl/304839183; van den Brink, Stieneke; Begthel, Harry; Verstegen, Monique M A; Cruz, Luis J; Hui, Lijian; van der Laan, Luc J W; de Jonge, Jeroen; Vries, Robert; Braakman, Eric; Mastrobattista, Enrico|info:eu-repo/dai/nl/228061105; Cornelissen, Jan J; Clevers, Hans|info:eu-repo/dai/nl/07164282X; Ten Berge, Derk

    2017-01-01

    Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature,

  18. Mesenchymal Stem Cell Therapy for Protection and Repair of Injured Vital Organs

    NARCIS (Netherlands)

    van Poll, D.; Parekkadan, B.; Rinkes, I. H. M. Borel; Tilles, A. W.; Yarmush, M. L.

    Recently there has been a paradigm shift in what is considered to be the therapeutic promise of mesenchymal stem cells (MSCs) in diseases of vital organs. Originally, research focused on MSCs as a source of regenerative cells by differentiation of transplanted cells into lost cell types. It is now

  19. Solid organ transplants following hematopoietic stem cell transplant in children.

    Science.gov (United States)

    Bunin, Nancy; Guzikowski, Virginia; Rand, Elizabeth R; Goldfarb, Samuel; Baluarte, Jorge; Meyers, Kevin; Olthoff, Kim M

    2010-12-01

    SOT may be indicated for a select group of pediatric patients who experience permanent organ failure following HSCT. However, there is limited information available about outcomes. We identified eight children at our center who received an SOT following an HSCT. Patients were six months to 18 yr at HSCT. Diseases for which children underwent HSCT included thalassemia, Wiskott-Aldrich syndrome, Shwachman-Diamond/bone marrow failure, sickle cell disease (SCD), erythropoietic porphyria (EP), ALL, chronic granulomatous disease, and neuroblastoma. Time from HSCT to SOT was 13 days to seven yr (median, 27 months. Lung SOT was performed for two patients with BO, kidney transplants for three patients, and liver transplants for three patients (VOD, chronic GVHD). Seven patients are alive with functioning allografts 6-180 months from SOT. Advances in organ procurement, operative technique, immunosuppressant therapy, and infection control may allow SOT for a select group of patients post-HSCT. However, scarcity of donor organs available in a timely fashion continues to be a limiting factor. Children who have undergone HSCT and develop single organ failure should be considered for an SOT if there is a high likelihood of cure of the primary disease. © 2010 John Wiley & Sons A/S.

  20. Organ-level quorum sensing directs regeneration in hair stem cell populations

    Science.gov (United States)

    Chen, Chih-Chiang; Wang, Lei; Plikus, Maksim V.; Jiang, Ting Xin; Murray, Philip J.; Ramos, Raul; Guerrero-Juarez, Christian F.; Hughes, Michael W; Lee, Oscar K.; Shi, Songtao; Widelitz, Randall B.; Lander, Arthur D.; Chuong, Cheng Ming

    2015-01-01

    SUMMARY Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair removal, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Removing hair at different densities leads to a regeneration of up to 5 times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells. PMID:25860610

  1. Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells

    Science.gov (United States)

    2017-09-01

    Determine if AngII promotes MB cell tumorigenicity through a AT1R-MYC positive feedback loop. This aim will build on our working model that AngII...AWARD NUMBER: W81XWH-14-1-0176 TITLE: Modeling Aggressive Medulloblastoma Using Human-Induced Pluripotent Stem Cells PRINCIPAL INVESTIGATOR...DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response

  2. Modelling of tomato stem diameter growth rate based on physiological responses

    International Nuclear Information System (INIS)

    Li, L.; Tan, J.; Lv, T.

    2017-01-01

    The stem diameter is an important parameter describing the growth of tomato plant during vegetative growth stage. A stem diameter growth model was developed to predict the response of plant growth under different conditions. By analyzing the diurnal variations of stem diameter in tomato (Solanum lycopersicum L.), it was found that the stem diameter measured at 3:00 am was the representative value as the daily basis of tomato stem diameter. Based on the responses of growth rate in stem diameter to light and temperature, a linear regression relationship was applied to establish the stem diameter growth rate prediction model for the vegetative growth stage in tomato and which was further validated by experiment. The root mean square error (RMSE) and relative error (RE) were used to test the correlation between measured and modeled stem diameter variations. Results showed that the model can be used in prediction for stem diameter growth rate at vegetative growth stage in tomato. (author)

  3. Retransformation bias in a stem profile model

    Science.gov (United States)

    Raymond L. Czaplewski; David Bruce

    1990-01-01

    An unbiased profile model, fit to diameter divided by diameter at breast height, overestimated volume of 5.3-m log sections by 0.5 to 3.5%. Another unbiased profile model, fit to squared diameter divided by squared diameter at breast height, underestimated bole diameters by 0.2 to 2.1%. These biases are caused by retransformation of the predicted dependent variable;...

  4. Model organisms and target discovery.

    Science.gov (United States)

    Muda, Marco; McKenna, Sean

    2004-09-01

    The wealth of information harvested from full genomic sequencing projects has not generated a parallel increase in the number of novel targets for therapeutic intervention. Several pharmaceutical companies have realized that novel drug targets can be identified and validated using simple model organisms. After decades of service in basic research laboratories, yeasts, worms, flies, fishes, and mice are now the cornerstones of modern drug discovery programs.: © 2004 Elsevier Ltd . All rights reserved.

  5. Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond.

    Science.gov (United States)

    Liu, Chun; Oikonomopoulos, Angelos; Sayed, Nazish; Wu, Joseph C

    2018-03-08

    The advent of human induced pluripotent stem cells (iPSCs) presents unprecedented opportunities to model human diseases. Differentiated cells derived from iPSCs in two-dimensional (2D) monolayers have proven to be a relatively simple tool for exploring disease pathogenesis and underlying mechanisms. In this Spotlight article, we discuss the progress and limitations of the current 2D iPSC disease-modeling platform, as well as recent advancements in the development of human iPSC models that mimic in vivo tissues and organs at the three-dimensional (3D) level. Recent bioengineering approaches have begun to combine different 3D organoid types into a single '4D multi-organ system'. We summarize the advantages of this approach and speculate on the future role of 4D multi-organ systems in human disease modeling. © 2018. Published by The Company of Biologists Ltd.

  6. Stemness of the organ of Corti relates to the epigenetic status of Sox2 enhancers.

    Directory of Open Access Journals (Sweden)

    Jörg Waldhaus

    Full Text Available In the adult mammalian auditory epithelium, the organ of Corti, loss of sensory hair cells results in permanent hearing loss. The underlying cause for the lack of regenerative response is the depletion of otic progenitors in the cell pool of the sensory epithelium. Here, we show that an increase in the sequence-specific methylation of the otic Sox2 enhancers NOP1 and NOP2 is correlated with a reduced self-renewal potential in vivo and in vitro; additionally, the degree of methylation of NOP1 and NOP2 is correlated with the dedifferentiation potential of postmitotic supporting cells into otic stem cells. Thus, the stemness the organ of Corti is related to the epigenetic status of the otic Sox2 enhancers. These observations validate the continued exploration of treatment strategies for dedifferentiating or reprogramming of differentiated supporting cells into progenitors to regenerate the damaged organ of Corti.

  7. Advances in pluripotent stem cell-derived endothelial cells: from biomaterials to organ regeneration.

    Science.gov (United States)

    Lui, Kathy O

    2014-01-01

    Human embryonic stem cells (ESCs), by virtue of their capability to self-renew and differentiate into a variety of cell types, represent the first type of pluripotent stem cells (PSCs) to be used in clinical transplantation during recent phase-I trials; however, it is still unclear whether hESC-derived tissues can self-organize and form part of the vascularized, functional organ following transplantation. Recently, endothelial cells (ECs) or angiogenic factors such as VEGFA have been demonstrated to support development and regeneration of multiple organ systems, including the heart, pancreas, liver, lung and bone marrow. Therefore, co-transplantation of ECs derived from the same parental PSCs that differentiate into cell types of interest; or overexpression of the inductive angiogenic factors responsible for organ regeneration might be beneficial to support function of hPSC-derived tissues. In this special issue, we discuss how protein kinases (Ng and colleagues); DNA methylation and histone modification (Tsui and colleagues) regulate cellular pluripotency and cell-fate specification of PSCs. In addition, we discuss how ECs and angiogenic factors could contribute to repair and regeneration of organs such as the heart (Yuan and colleagues), the cardiovascular system (Tse and colleagues) and the pancreas (Lui). We also discuss the role of mesenchymal stem cells or paracrine factors secreted by them in tissue repair (Li and colleagues). Lastly, we discuss how to generate self-organized and vascularized tissues derived from PSCs in a 2- or 3-dimensional format by fusing tissue bioengineering approaches with stem cell technology (Chen).

  8. Early metabolic/cellular-level resuscitation following terminal brain stem herniation: implications for organ transplantation.

    Science.gov (United States)

    Arbour, Richard B

    2013-01-01

    Patients with terminal brain stem herniation experience global physiological consequences and represent a challenging population in critical care practice as a result of multiple factors. The first factor is severe depression of consciousness, with resulting compromise in airway stability and lung ventilation. Second, with increasing severity of brain trauma, progressive brain edema, mass effect, herniation syndromes, and subsequent distortion/displacement of the brain stem follow. Third, with progression of intracranial pathophysiology to terminal brain stem herniation, multisystem consequences occur, including dysfunction of the hypothalamic-pituitary axis, depletion of stress hormones, and decreased thyroid hormone bioavailability as well as biphasic cardiovascular state. Cardiovascular dysfunction in phase 1 is a hyperdynamic and hypertensive state characterized by elevated systemic vascular resistance and cardiac contractility. Cardiovascular dysfunction in phase 2 is a hypotensive state characterized by decreased systemic vascular resistance and tissue perfusion. Rapid changes along the continuum of hyperperfusion versus hypoperfusion increase risk of end-organ damage, specifically pulmonary dysfunction from hemodynamic stress and high-flow states as well as ischemic changes consequent to low-flow states. A pronounced inflammatory state occurs, affecting pulmonary function and gas exchange and contributing to hemodynamic instability as a result of additional vasodilatation. Coagulopathy also occurs as a result of consumption of clotting factors as well as dilution of clotting factors and platelets consequent to aggressive crystalloid administration. Each consequence of terminal brain stem injury complicates clinical management within this patient demographic. In general, these multisystem consequences are managed with mechanism-based interventions within the context of caring for the donor's organs (liver, kidneys, heart, etc.) after death by neurological

  9. In vitro models of cancer stem cells and clinical applications.

    Science.gov (United States)

    S Franco, Sara; Szczesna, Karolina; Iliou, Maria S; Al-Qahtani, Mohammed; Mobasheri, Ali; Kobolák, Julianna; Dinnyés, András

    2016-09-30

    Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current non-surgical treatments can cure cancer effectively. The reason could be due to the subpopulation called "cancer stem cells" (CSCs), being defined as those cells within a tumour that have properties of stem cells: self-renewal and the ability for differentiation into multiple cell types that occur in tumours.The phenomenon of CSCs is based on their resistance to many of the current cancer therapies, which results in tumour relapse. Although further investigation regarding CSCs is still needed, there is already evidence that these cells may play an important role in the prognosis of cancer, progression and therapeutic strategy. Therefore, long-term patient survival may depend on the elimination of CSCs. Consequently, isolation of pure CSC populations or reprogramming of cancer cells into CSCs, from cancer cell lines or primary tumours, would be a useful tool to gain an in-depth knowledge about heterogeneity and plasticity of CSC phenotypes and therefore carcinogenesis. Herein, we will discuss current CSC models, methods used to characterize CSCs, candidate markers, characteristic signalling pathways and clinical applications of CSCs. Some examples of CSC-specific treatments that are currently in early clinical phases will also be presented in this review.

  10. GRAFTING FOR THE RECOVERY OF YELLOW PASSION FRUIT STEM IN ORGANIC SYSTEM

    Directory of Open Access Journals (Sweden)

    MARIA IZABEL FREITAS LINS REZENDE

    Full Text Available ABSTRACT The aim of the present study was to evaluate the effect of stem repair grafting on the recovery of damaged plants, yield and quality of yellow passion fruits in organic system. The experiment was conducted simulating five stem damages (treatments in randomized complete block design with four replications of four plants each. After reaching on average 7.3 ± 1.2 mm in stem diameter, plants were perforated at 20, 40, 60 and 80% of the stem diameter with the aid of a steel drill. The reduction in plant stand treatment with 80 % damage reduces plant productivity. Then, bridge-type grafting was performed by connecting the top and bottom of the injury. The grafting success percentage ranged from 81.3 to 95.8% and did not differ between treatments, but the survival rate of plants was lower in treatments with 40 and 80% of injuries. There were no statistically significant differences between treatments for the following variables: number of fruits per plant, average fruit weight, total soluble solids (TSS, total titratable acidity (TTA and (TSS/TTA ratio. Recovery stem grafting allows injured plants to maintain the same productivity by up to 60% compared to plants without injuries.

  11. Modeling Human Cardiac Hypertrophy in Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Ekaterina Ovchinnikova

    2018-03-01

    Full Text Available Summary: Cardiac hypertrophy accompanies many forms of cardiovascular diseases. The mechanisms behind the development and regulation of cardiac hypertrophy in the human setting are poorly understood, which can be partially attributed to the lack of a human cardiomyocyte-based preclinical test system recapitulating features of diseased myocardium. The objective of our study is to determine whether human embryonic stem cell-derived cardiomyocytes (hESC-CMs subjected to mechanical stretch can be used as an adequate in vitro model for studying molecular mechanisms of cardiac hypertrophy. We show that hESC-CMs subjected to cyclic stretch, which mimics mechanical overload, exhibit essential features of a hypertrophic state on structural, functional, and gene expression levels. The presented hESC-CM stretch approach provides insight into molecular mechanisms behind mechanotransduction and cardiac hypertrophy and lays groundwork for the development of pharmacological approaches as well as for discovering potential circulating biomarkers of cardiac dysfunction. : In this article, Berezikov, van der Meer, and colleagues used stem cell-derived cardiomyocytes to model human cardiac hypertrophy. Their approach provides novel insights into molecular mechanisms behind mechanotransduction and cardiac hypertrophy and lays groundwork for the development of new pharmacological approaches as well as for discovering new potential circulating biomarkers of cardiac dysfunction. Keywords: stem cells, human cardiomyocytes, hypertrophy, in vitro disease modeling, cardiomyocytes stretch response, mechanotransduction

  12. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    Energy Technology Data Exchange (ETDEWEB)

    Gross, Emilie; Quillet-Mary, Anne [INSERM, UMR1037-Cancer Research Center of Toulouse, 31300 Toulouse (France); ERL 5294 CNRS, BP3028 CHU Purpan, 31300 Toulouse (France); Université Toulouse III Paul-Sabatier, 31300 Toulouse (France); Ysebaert, Loic; Laurent, Guy [INSERM, UMR1037-Cancer Research Center of Toulouse, 31300 Toulouse (France); ERL 5294 CNRS, BP3028 CHU Purpan, 31300 Toulouse (France); Université Toulouse III Paul-Sabatier, 31300 Toulouse (France); Service d' Hématologie, CHU Purpan, 31300 Toulouse (France); Fournie, Jean-Jacques, E-mail: jean-jacques.fournie@inserm.fr [INSERM, UMR1037-Cancer Research Center of Toulouse, 31300 Toulouse (France); ERL 5294 CNRS, BP3028 CHU Purpan, 31300 Toulouse (France); Université Toulouse III Paul-Sabatier, 31300 Toulouse (France)

    2011-03-25

    The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

  13. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    International Nuclear Information System (INIS)

    Gross, Emilie; Quillet-Mary, Anne; Ysebaert, Loic; Laurent, Guy; Fournie, Jean-Jacques

    2011-01-01

    The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity

  14. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Fournie

    2011-03-01

    Full Text Available The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

  15. Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids

    Directory of Open Access Journals (Sweden)

    Lam-Phuong Nguyen DO

    2016-04-01

    Full Text Available Acute fibrinous and organizing pneumonia (AFOP is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

  16. [Regeneration of vertebrate appendage: an old experimental model to study stem cells in the adult].

    Science.gov (United States)

    Tawk, Marcel; Vriz, Sophie

    2003-04-01

    The application of stem cell therapy to cure degenerative diseases offers immense possibilities, but the research in this field is the subject of ethical debates raised by the question of destructive research on early human embryos. Stem cells taken in the adult constitute an alternative to human embryonic stem cells, but our knowledge on totipotent or pluripotent cells is currently insufficient. Furthermore, many questions must be solved before selection and differentiation of these cells in a given cellular type can be controlled on a routine basis. What are the molecular characteristics of an adult stem cell? What are the mechanisms involved in cell reprogramming? Which signals control stem cell replication and differentiation? Basic research activities must be carried out in order to clarify all these points. In this context, the regeneration of vertebrate appendages provides a model for this type of research. The regeneration process is defined by both the morphological and functional reconstruction of a part of a living organism, which has previously been destroyed. But why are some vertebrates able to regenerate complex structures and others apparently not? Among most vertebrates, the capacity to regenerate is limited to some tissues. It is however possible to observe the regeneration of appendages (limb, tail, fin, jaw, etc.) among several amphibians and fish. This regeneration leads to re-forming of the amputated part with a complete restoration of its shape, segmentation and function. Why is the amputation of limbs not followed by regeneration in mammals and birds: absence of stem cells, absence of recruitment signals for these cells, or absence of signal receptivity? This review constitutes a report on the current understanding of the basis of on regeneration of legs in tetrapods and of fins in fish with an emphasis in the role of the nervous system in this process.

  17. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models.

    Science.gov (United States)

    Sandoe, Jackson; Eggan, Kevin

    2013-07-01

    Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Recent advances in pluripotent stem cell technology now grant access to substantial quantities of disease-pertinent neurons both with and without predisposing mutations. While this suite of technologies has revolutionized the field of 'in vitro disease modeling', great care must be taken in their deployment if robust, durable discoveries are to be made. Here we review what we perceive to be several of the stumbling blocks in the use of stem cells for the study of neurological disease and offer strategies to overcome them.

  18. Self-Organization of Spatial Patterning in Human Embryonic Stem Cells.

    Science.gov (United States)

    Deglincerti, Alessia; Etoc, Fred; Ozair, M Zeeshan; Brivanlou, Ali H

    2016-01-01

    The developing embryo is a remarkable example of self-organization, where functional units are created in a complex spatiotemporal choreography. Recently, human embryonic stem cells (ESCs) have been used to recapitulate in vitro the self-organization programs that are executed in the embryo in vivo. This represents an unique opportunity to address self-organization in humans that is otherwise not addressable with current technologies. In this chapter, we review the recent literature on self-organization of human ESCs, with a particular focus on two examples: formation of embryonic germ layers and neural rosettes. Intriguingly, both activation and elimination of TGFβ signaling can initiate self-organization, albeit with different molecular underpinnings. We discuss the mechanisms underlying the formation of these structures in vitro and explore future challenges in the field. © 2016 Elsevier Inc. All rights reserved.

  19. The sexual identity of adult intestinal stem cells controls organ size and plasticity

    Science.gov (United States)

    Hudry, Bruno; Khadayate, Sanjay; Miguel-Aliaga, Irene

    2016-01-01

    SUMMARY Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realisation that cell-intrinsic mechanisms play important and persistent roles1,2. Here we use the Drosophila melanogaster intestine to investigate the nature and significance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncover its key roles in controlling organ size, its reproductive plasticity and its response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms, which control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognised. PMID:26887495

  20. Adult stem cells in mice : visualization and characterization using genetic mouse models

    NARCIS (Netherlands)

    Snippert, H.J.G.

    2011-01-01

    The onset of each living organism starts with pluripotent stem cells that have the ability to differentiate into all the different cell types of an organism. However, during the earliest stages of development, the pluripotent stem cells will stepwise lose their developmental potential. The cells

  1. Stem cells in skin regeneration: biomaterials and computational models

    Directory of Open Access Journals (Sweden)

    Daniele eTartarini

    2016-01-01

    Full Text Available The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles, has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells have been proposed for the treatment of these wounds, thanks to the ability of stem cells to self-renew and specifically differentiate in response to the target bimolecular environment. Here we discuss how advanced biomedical devices can be developed by combining stem cells with properly engineered biomaterials and computational models. Examples include composite skin substitutes and bioactive dressings with controlled porosity and surface topography for controlling the infiltration and differentiation of the cells. In this scenario, mathematical frameworks for the simulation of cell population growth can provide support for the design of bio-constructs, reducing the need of expensive, time-consuming and ethically controversial animal experimentation.

  2. Induced pluripotent stem cell models of lysosomal storage disorders

    Directory of Open Access Journals (Sweden)

    Daniel K. Borger

    2017-06-01

    Full Text Available Induced pluripotent stem cells (iPSCs have provided new opportunities to explore the cell biology and pathophysiology of human diseases, and the lysosomal storage disorder research community has been quick to adopt this technology. Patient-derived iPSC models have been generated for a number of lysosomal storage disorders, including Gaucher disease, Pompe disease, Fabry disease, metachromatic leukodystrophy, the neuronal ceroid lipofuscinoses, Niemann-Pick types A and C1, and several of the mucopolysaccharidoses. Here, we review the strategies employed for reprogramming and differentiation, as well as insights into disease etiology gleaned from the currently available models. Examples are provided to illustrate how iPSC-derived models can be employed to develop new therapeutic strategies for these disorders. We also discuss how models of these rare diseases could contribute to an enhanced understanding of more common neurodegenerative disorders such as Parkinson’s disease, and discuss key challenges and opportunities in this area of research.

  3. Stem Measurements and Taper Modeling Using Photogrammetric Point Clouds

    Directory of Open Access Journals (Sweden)

    Rong Fang

    2017-07-01

    Full Text Available The estimation of tree biomass and the products that can be obtained from a tree stem have focused forest research for more than two centuries. Traditionally, measurements of the entire tree bole were expensive or inaccurate, even when sophisticated remote sensing techniques were used. We propose a fast and accurate procedure for measuring diameters along the merchantable portion of the stem at any given height. The procedure uses unreferenced photos captured with a consumer grade camera. A photogrammetric point cloud (PPC is produced from the acquired images using structure from motion, which is a computer vision range imaging technique. A set of 18 loblolly pines (Pinus taeda Lindl. from east Louisiana, USA, were photographed, subsequently cut, and the diameter measured every meter. The same diameters were measured on the point cloud with AutoCAD Civil3D. The ground point cloud reconstruction provided useful information for at most 13 m along the stem. The PPC measurements are biased, overestimating real diameters by 17.2 mm, but with a reduced standard deviation (8.2%. A linear equation with parameters of the error at a diameter at breast height (d1.3 and the error of photogrammetric rendering reduced the bias to 1.4 mm. The usability of the PPC measurements in taper modeling was assessed with four models: Max and Burkhart [1], Baldwin and Feduccia [2], Lenhart et al. [3], and Kozak [4]. The evaluation revealed that the data fit well with all the models (R2 ≥ 0.97, with the Kozak and the Baldwin and Feduccia performing the best. The results support the replacement of taper with PPC, as faster, and more accurate and precise product estimations are expected.

  4. Smed-SmB, a member of the LSm protein superfamily, is essential for chromatoid body organization and planarian stem cell proliferation.

    Science.gov (United States)

    Fernandéz-Taboada, Enrique; Moritz, Sören; Zeuschner, Dagmar; Stehling, Martin; Schöler, Hans R; Saló, Emili; Gentile, Luca

    2010-04-01

    Planarians are an ideal model system to study in vivo the dynamics of adult pluripotent stem cells. However, our knowledge of the factors necessary for regulating the 'stemness' of the neoblasts, the adult stem cells of planarians, is sparse. Here, we report on the characterization of the first planarian member of the LSm protein superfamily, Smed-SmB, which is expressed in stem cells and neurons in Schmidtea mediterranea. LSm proteins are highly conserved key players of the splicing machinery. Our study shows that Smed-SmB protein, which is localized in the nucleus and the chromatoid body of stem cells, is required to safeguard the proliferative ability of the neoblasts. The chromatoid body, a cytoplasmatic ribonucleoprotein complex, is an essential regulator of the RNA metabolism required for the maintenance of metazoan germ cells. However, planarian neoblasts and neurons also rely on its functions. Remarkably, Smed-SmB dsRNA-mediated knockdown results in a rapid loss of organization of the chromatoid body, an impairment of the ability to post-transcriptionally process the transcripts of Smed-CycB, and a severe proliferative failure of the neoblasts. This chain of events leads to a quick depletion of the neoblast pool, resulting in a lethal phenotype for both regenerating and intact animals. In summary, our results suggest that Smed-SmB is an essential component of the chromatoid body, crucial to ensure a proper RNA metabolism and essential for stem cell proliferation.

  5. Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

    Science.gov (United States)

    Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

    2016-03-31

    The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

  6. Mathematical Models of Pluripotent Stem Cells: At the Dawn of Predictive Regenerative Medicine.

    Science.gov (United States)

    Pir, Pınar; Le Novère, Nicolas

    2016-01-01

    Regenerative medicine, ranging from stem cell therapy to organ regeneration, is promising to revolutionize treatments of diseases and aging. These approaches require a perfect understanding of cell reprogramming and differentiation. Predictive modeling of cellular systems has the potential to provide insights about the dynamics of cellular processes, and guide their control. Moreover in many cases, it provides alternative to experimental tests, difficult to perform for practical or ethical reasons. The variety and accuracy of biological processes represented in mathematical models grew in-line with the discovery of underlying molecular mechanisms. High-throughput data generation led to the development of models based on data analysis, as an alternative to more established modeling based on prior mechanistic knowledge. In this chapter, we give an overview of existing mathematical models of pluripotency and cell fate, to illustrate the variety of methods and questions. We conclude that current approaches are yet to overcome a number of limitations: Most of the computational models have so far focused solely on understanding the regulation of pluripotency, and the differentiation of selected cell lineages. In addition, models generally interrogate only a few biological processes. However, a better understanding of the reprogramming process leading to ESCs and iPSCs is required to improve stem-cell therapies. One also needs to understand the links between signaling, metabolism, regulation of gene expression, and the epigenetics machinery.

  7. Modeling Genomic Imprinting Disorders Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Chamberlain, Stormy J; Germain, Noelle D; Chen, Pin-Fang; Hsiao, Jack S; Glatt-Deeley, Heather

    2016-01-01

    Induced pluripotent stem cell (iPSC) technology has allowed for the invaluable modeling of many genetic disorders including disorders associated with genomic imprinting. Genomic imprinting involves differential DNA and histone methylation and results in allele-specific gene expression. Most of the epigenetic marks in somatic cells are erased and reestablished during the process of reprogramming into iPSCs. Therefore, in generating models of disorders associated with genomic imprinting, it is important to verify that the imprinting status and allele-specific gene expression patterns of the parental somatic cells are maintained in their derivative iPSCs. Here, we describe three techniques: DNA methylation analysis, allele-specific PCR, and RNA FISH, which we use to analyze genomic imprinting in iPSC models of neurogenetic disorders involving copy number variations of the chromosome 15q11-q13 region.

  8. A SCARECROW-RETINOBLASTOMA Protein Network Controls Protective Quiescence in the Arabidopsis Root Stem Cell Organizer

    NARCIS (Netherlands)

    Cruz-Ramirez, A.; Diaz Trivino, S.; Wachsman, G.; Du, Y.; Arteága-Vázquez, M.; Zhang Hongtao,; Benjamins, R.; Blilou, I.; Neef, A.B.; Chandler, V.; Scheres, B.

    2013-01-01

    Quiescent long-term somatic stem cells reside in plant and animal stem cell niches. Within the Arabidopsis root stem cell population, the Quiescent Centre (QC), which contains slowly dividing cells, maintains surrounding short-term stem cells and may act as a long-term reservoir for stem cells. The

  9. Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective

    Science.gov (United States)

    Heffernan, John M.; Sirianni, Rachael W.

    2018-02-01

    Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.

  10. Modeling Neurological Disorders by Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Tanut Kunkanjanawan

    2011-01-01

    Full Text Available Studies of human brain development are critical as research on neurological disorders have been progressively advanced. However, understanding the process of neurogenesis through analysis of the early embryo is complicated and limited by a number of factors, including the complexity of the embryos, availability, and ethical constrains. The emerging of human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs has shed light of a new approach to study both early development and disease pathology. The cells behave as precursors of all embryonic lineages; thus, they allow tracing the history from the root to individual branches of the cell lineage tree. Systems for neural differentiation of hESCs and iPSCs have provided an experimental model that can be used to augment in vitro studies of in vivo brain development. Interestingly, iPSCs derived from patients, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. This paper summarizes the recent reports of the development of iPSCs from patients who suffer from neurological diseases and evaluates the feasibility of iPSCs as a disease model. The benefits and obstacles of iPSC technology are highlighted in order to raising the cautions of misinterpretation prior to further clinical translations.

  11. Advances in stem cells and regenerative medicine: single-cell dynamics, new models and translational perspectives.

    Science.gov (United States)

    Twigger, Alecia-Jane; Scheel, Christina H

    2017-09-01

    An international cohort of over 300 stem cell biologists came together in Heidelberg, Germany in May 2017 as delegates of the 'Advances in Stem Cells and Regenerative Medicine' conference run through the European Molecular Biology Organization. This Meeting Review highlights the novel insights into stem cell regulation, new technologies aiding in discovery and exciting breakthroughs in the field of regenerative medicine that emerged from the meeting. © 2017. Published by The Company of Biologists Ltd.

  12. The Potential of the Combination of CRISPR/Cas9 and Pluripotent Stem Cells to Provide Human Organs from Chimaeric Pigs

    Directory of Open Access Journals (Sweden)

    Wanyou Feng

    2015-03-01

    Full Text Available Clinical organ allotransplantation is limited by the availability of deceased human donors. However, the transplantation of human organs produced in other species would provide an unlimited number of organs. The pig has been identified as the most suitable source of organs for humans as organs of any size would be available. Genome editing by RNA-guided endonucleases, also known as clustered regularly interspaced short palindromic repeat (CRISPR/Cas9, in combination with induced pluripotent stem cells (iPSC, may have the potential to enable the creation of human organs from genetically-modified chimaeric pigs. These could potentially provide an unlimited supply of organs that would not be rejected by the recipient’s immune system. However, substantial research is needed to prove that this approach will work. Genetic modification of chimaeric pigs could also provide useful models for developing therapies for various human diseases, especially in relation to drug development.

  13. Organization Development: Strategies and Models.

    Science.gov (United States)

    Beckhard, Richard

    This book, written for managers, specialists, and students of management, is based largely on the author's experience in helping organization leaders with planned-change efforts, and on related experience of colleagues in the field. Chapter 1 presents the background and causes for the increased concern with organization development and planned…

  14. Stem cell contributions to neurological disease modeling and personalized medicine.

    Science.gov (United States)

    Liang, Nicholas; Trujillo, Cleber A; Negraes, Priscilla D; Muotri, Alysson R; Lameu, Claudiana; Ulrich, Henning

    2018-01-03

    Human induced pluripotent stem cells (iPSCs) represent a revolutionary tool for disease modeling and drug discovery. The generation of tissue-relevant cell types exhibiting a patient's genetic and molecular background offers the ability to develop individual and effective therapies. In this review, we present some major achievements in the neuroscience field using iPSCs and discuss promising perspectives in personalized medicine. In addition to disease modeling, the understanding of the cellular and molecular basis of neurological disorders is explored, including the discovery of new targets and potential drugs. Ultimately, we highlight how iPSC technology, together with genome editing approaches, may bring a deep impact on pre-clinical trials by reducing costs and increasing the success of treatments in a personalized fashion. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Modeling human neurological disorders with induced pluripotent stem cells.

    Science.gov (United States)

    Imaizumi, Yoichi; Okano, Hideyuki

    2014-05-01

    Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained

  16. Probabilistic Modeling of Reprogramming to Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Liu, Lin L; Brumbaugh, Justin; Bar-Nur, Ori; Smith, Zachary; Stadtfeld, Matthias; Meissner, Alexander; Hochedlinger, Konrad; Michor, Franziska

    2016-12-20

    Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is typically an inefficient and asynchronous process. A variety of technological efforts have been made to accelerate and/or synchronize this process. To define a unified framework to study and compare the dynamics of reprogramming under different conditions, we developed an in silico analysis platform based on mathematical modeling. Our approach takes into account the variability in experimental results stemming from probabilistic growth and death of cells and potentially heterogeneous reprogramming rates. We suggest that reprogramming driven by the Yamanaka factors alone is a more heterogeneous process, possibly due to cell-specific reprogramming rates, which could be homogenized by the addition of additional factors. We validated our approach using publicly available reprogramming datasets, including data on early reprogramming dynamics as well as cell count data, and thus we demonstrated the general utility and predictive power of our methodology for investigating reprogramming and other cell fate change systems. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Probabilistic Modeling of Reprogramming to Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Lin L. Liu

    2016-12-01

    Full Text Available Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs is typically an inefficient and asynchronous process. A variety of technological efforts have been made to accelerate and/or synchronize this process. To define a unified framework to study and compare the dynamics of reprogramming under different conditions, we developed an in silico analysis platform based on mathematical modeling. Our approach takes into account the variability in experimental results stemming from probabilistic growth and death of cells and potentially heterogeneous reprogramming rates. We suggest that reprogramming driven by the Yamanaka factors alone is a more heterogeneous process, possibly due to cell-specific reprogramming rates, which could be homogenized by the addition of additional factors. We validated our approach using publicly available reprogramming datasets, including data on early reprogramming dynamics as well as cell count data, and thus we demonstrated the general utility and predictive power of our methodology for investigating reprogramming and other cell fate change systems.

  18. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan

    2012-07-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  19. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    Science.gov (United States)

    Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O2 pressure (pO2) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2 to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases. PMID:22224628

  20. Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres [Oslo University Hospital-Rikshospitalet, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); Bargallo, Nuria [Universitat de Barcelona, Section of Neuroradiology, Department of Radiology, Hospital Clinic, Barcelona (Spain); Institut d' investigacions Biomediques August Pi i Sunyer (IDIBARS), Resonance Magnetic Image Core Facility, Barcelona (Spain); Floeisand, Yngvar [Oslo University Hospital-Rikshospitalet, Department of Hematology, Oslo (Norway); Sponheim, Jon [Oslo University Hospital-Rikshospitalet, Section of Gastroenterology, Department of Transplantation Medicine, Oslo (Norway); Graus, Francesc [Universitat de Barcelona, Department of Neurology, Hospital Clinic, Barcelona (Spain); Institut d' investigacions Biomediques August Pi i Sunyer (IDIBARS), Neuroimmunology Program, Barcelona (Spain); Hald, John K. [Oslo University Hospital-Rikshospitalet, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Faculty of Medicine, Oslo (Norway)

    2017-02-15

    Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months. Further differentiation will be based on etiology: infections, drug toxicity, metabolic derangements, cerebrovascular complications, and posttransplantation malignancies. In addition, differentiation will be based on complications specific to the type of transplantation: allogeneic and autologous hematopoietic stem cells (HSC), heart, lung, kidney, pancreas, and liver. Thus, in this article we emphasize the strategic role of neuroradiology in the diagnosis and response to treatment by utilizing a methodical approach in the work up of patients with neurologic complications after transplantation. (orig.)

  1. Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation

    International Nuclear Information System (INIS)

    Server, Andres; Bargallo, Nuria; Floeisand, Yngvar; Sponheim, Jon; Graus, Francesc; Hald, John K.

    2017-01-01

    Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months. Further differentiation will be based on etiology: infections, drug toxicity, metabolic derangements, cerebrovascular complications, and posttransplantation malignancies. In addition, differentiation will be based on complications specific to the type of transplantation: allogeneic and autologous hematopoietic stem cells (HSC), heart, lung, kidney, pancreas, and liver. Thus, in this article we emphasize the strategic role of neuroradiology in the diagnosis and response to treatment by utilizing a methodical approach in the work up of patients with neurologic complications after transplantation. (orig.)

  2. APPLICATION OF STEM CELLS AND PRECURSOR CELLS FOR STIMULATION OF ORGAN REVASCULARIZATION AND REGENERATION

    Directory of Open Access Journals (Sweden)

    M. V. Eremeeva

    2010-01-01

    Full Text Available Different angiogenic factors induced angiogenesis stimulation in ischemic tissues stays in the focus of scientific research for long time. The key role in ischemic angiogenesis belongs to endothelial precursor cells, plenty of which are reserved in bone marrow. Resident endothelial precursor cells are also found in some tissues and in circulation. These cells are involved in neoangiogenesis as well. Theoretically, injection of exogeneous endothelial precusor cells might contribute to restoration of circulation in the ischemic organ. Various types of cells have been approved for regeneration stimulation in a number of experimental protocols. A various degree of improvement of myocardial contractive function has been obtained as a universal result of these investigations, though the mechanisms underlying observed effect remain evasive. The paper focuses on advantages and drawbacks of embryonic, hematopoetic and mesenhimal stem cells application for angiogenesis stimulation and organs and tissues regeneration. 

  3. Fruit tree model for uptake of organic compounds from soil

    DEFF Research Database (Denmark)

    Trapp, Stefan; Rasmussen, D.; Samsoe-Petersen, L.

    2003-01-01

    rences: 20 [ view related records ] Citation Map Abstract: Apples and other fruits are frequently cultivated in gardens and are part of our daily diet. Uptake of pollutants into apples may therefore contribute to the human daily intake of toxic substances. In current risk assessment of polluted...... soils, regressions or models are in use, which were not intended to be used for tree fruits. A simple model for uptake of neutral organic contaminants into fruits is developed. It considers xylem and phloem transport to fruits through the stem. The mass balance is solved for the steady......-state, and an example calculation is given. The Fruit Tree Model is compared to the empirical equation of Travis and Arms (T&A), and to results from fruits, collected in contaminated areas. For polar compounds, both T&A and the Fruit Tree Model predict bioconcentration factors fruit to soil (BCF, wet weight based...

  4. Which bank? A guardian model for regulation of embryonic stem cell research in Australia.

    Science.gov (United States)

    McLennan, A

    2007-08-01

    In late 2005 the Legislation Review: Prohibition of Human Cloning Act 2002 (Cth) and the Research Involving Human Embryos Act 2002 (Cth) recommended the establishment of an Australian stem cell bank. This article aims to address a lack of discussion of issues surrounding stem cell banking by suggesting possible answers to the questions of whether Australia should establish a stem cell bank and what its underlying philosophy and functions should be. Answers are developed through an analysis of regulatory, scientific and intellectual property issues relating to embryonic stem cell research in the United Kingdom, United States and Australia. This includes a detailed analysis of the United Kingdom Stem Cell Bank. It is argued that a "guardian" model stem cell bank should be established in Australia. This bank would aim to promote the maximum public benefit from human embryonic stem cell research by providing careful regulatory oversight and addressing ethical issues, while also facilitating research by addressing practical scientific concerns and intellectual property issues.

  5. Modeling Neuropsychiatric and Neurodegenerative Diseases With Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth A. LaMarca

    2018-04-01

    Full Text Available Human-induced pluripotent stem cells (hiPSCs have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional “mini-brains” and clustered, regularly interspersed short palindromic repeats (CRISPR-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson’s disease, and consider the future of this groundbreaking research.

  6. Model Organisms Fact Sheet: Using Model Organisms to Study Health and Disease

    Science.gov (United States)

    ... research organisms to explore the basic biology and chemistry of life. Scientists decide which organism to study ... and much is already known about their genetic makeup . For these and other reasons, studying model organisms ...

  7. Modeling Neurovascular Disorders and Therapeutic Outcomes with Human-Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Allison M. Bosworth

    2018-01-01

    Full Text Available The neurovascular unit (NVU is composed of neurons, astrocytes, pericytes, and endothelial cells that form the blood–brain barrier (BBB. The NVU regulates material exchange between the bloodstream and the brain parenchyma, and its dysfunction is a primary or secondary cause of many cerebrovascular and neurodegenerative disorders. As such, there are substantial research thrusts in academia and industry toward building NVU models that mimic endogenous organization and function, which could be used to better understand disease mechanisms and assess drug efficacy. Human pluripotent stem cells, which can self-renew indefinitely and differentiate to almost any cell type in the body, are attractive for these models because they can provide a limitless source of individual cells from the NVU. In addition, human-induced pluripotent stem cells (iPSCs offer the opportunity to build NVU models with an explicit genetic background and in the context of disease susceptibility. Herein, we review how iPSCs are being used to model neurovascular and neurodegenerative diseases, with particular focus on contributions of the BBB, and discuss existing technologies and emerging opportunities to merge these iPSC progenies with biomaterials platforms to create complex NVU systems that recreate the in vivo microenvironment.

  8. Potent tumor tropism of induced pluripotent stem cells and induced pluripotent stem cell-derived neural stem cells in the mouse intracerebral glioma model.

    Science.gov (United States)

    Yamazoe, Tomohiro; Koizumi, Shinichiro; Yamasaki, Tomohiro; Amano, Shinji; Tokuyama, Tsutomu; Namba, Hiroki

    2015-01-01

    Although neural and mesenchymal stem cells have been well-known to have a strong glioma tropism, this activity in induced pluripotent stem cells (iPSCs) has not yet been fully studied. In the present study, we tested tumor tropic activity of mouse iPSCs and neural stem cells derived from the iPSC (iPS-NSCs) using in vitro Matrigel invasion chamber assay and in vivo mouse intracranial tumor model. Both iPSC and iPS-NSC had a similar potent in vitro tropism for glioma conditioned media. The migrated iPSCs to the gliomas kept expressing Nanog-GFP gene, suggesting no neuronal or glial differentiation. iPSCs or iPS-NSCs labeled with 5-bromo-2-deoxyuridine were intracranially implanted in the contralateral hemisphere to the GL261 glioma cell implantation in the allogeneic C57BL/6 mouse. Active migration of both stem cells was observed 7 days after implantation. Again, the iPSCs located in the tumor area expressed Nanog-GFP gene, suggesting that the migrated cells were still iPSCs. These findings demonstrated that both iPSCs and iPS-NSCs had potent glioma tropism and could be candidates as vehicles in stem cell-based glioma therapy.

  9. Incorporating additional tree and environmental variables in a lodgepole pine stem profile model

    Science.gov (United States)

    John C. Byrne

    1993-01-01

    A new variable-form segmented stem profile model is developed for lodgepole pine (Pinus contorta) trees from the northern Rocky Mountains of the United States. I improved estimates of stem diameter by predicting two of the model coefficients with linear equations using a measure of tree form, defined as a ratio of dbh and total height. Additional improvements were...

  10. Modelling organic particles in the atmosphere

    International Nuclear Information System (INIS)

    Couvidat, Florian

    2012-01-01

    Organic aerosol formation in the atmosphere is investigated via the development of a new model named H 2 O (Hydrophilic/Hydrophobic Organics). First, a parameterization is developed to take into account secondary organic aerosol formation from isoprene oxidation. It takes into account the effect of nitrogen oxides on organic aerosol formation and the hydrophilic properties of the aerosols. This parameterization is then implemented in H 2 O along with some other developments and the results of the model are compared to organic carbon measurements over Europe. Model performance is greatly improved by taking into account emissions of primary semi-volatile compounds, which can form secondary organic aerosols after oxidation or can condense when temperature decreases. If those emissions are not taken into account, a significant underestimation of organic aerosol concentrations occurs in winter. The formation of organic aerosols over an urban area was also studied by simulating organic aerosols concentration over the Paris area during the summer campaign of Megapoli (July 2009). H 2 O gives satisfactory results over the Paris area, although a peak of organic aerosol concentrations from traffic, which does not appear in the measurements, appears in the model simulation during rush hours. It could be due to an underestimation of the volatility of organic aerosols. It is also possible that primary and secondary organic compounds do not mix well together and that primary semi volatile compounds do not condense on an organic aerosol that is mostly secondary and highly oxidized. Finally, the impact of aqueous-phase chemistry was studied. The mechanism for the formation of secondary organic aerosol includes in-cloud oxidation of glyoxal, methylglyoxal, methacrolein and methylvinylketone, formation of methyltetrols in the aqueous phase of particles and cloud droplets, and the in-cloud aging of organic aerosols. The impact of wet deposition is also studied to better estimate the

  11. Stem Cells as In Vitro Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Patricia L. Martínez-Morales

    2012-01-01

    Full Text Available Progress in understanding neurodegenerative cell biology in Parkinson's disease (PD has been hampered by a lack of predictive and relevant cellular models. In addition, the lack of an adequate in vitro human neuron cell-based model has been an obstacle for the uncover of new drugs for treating PD. The ability to generate induced pluripotent stem cells (iPSCs from PD patients and a refined capacity to differentiate these iPSCs into DA neurons, the relevant disease cell type, promises a new paradigm in drug development that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSC that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSC can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling PD “in a dish” and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets, and enhance the probability of clinical success of new drugs.

  12. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Rishindra M., E-mail: reddyrm@med.umich.edu [Medical Center, University of Michigan, 1500 E. Medical Center Drive, 2120 Taubman Center, Ann Arbor, MI 48109 (United States); Kakarala, Madhuri; Wicha, Max S. [Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (United States)

    2011-06-20

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples.

  13. Very small embryonic/epiblast-like stem cells (VSELs) and their potential role in aging and organ rejuvenation--an update and comparison to other primitive small stem cells isolated from adult tissues.

    Science.gov (United States)

    Ratajczak, Mariusz Z; Shin, Dong-Myung; Liu, Rui; Mierzejewska, Kasia; Ratajczak, Janina; Kucia, Magda; Zuba-Surma, Ewa K

    2012-04-01

    Very small embryonic-like stem cells (VSELs) are a population of developmentally early stem cells residing in adult tissues. These rare cells, which are slightly smaller than red blood cells, i) become mobilized during stress situations into peripheral blood, ii) are enriched in the Sca1+Lin-CD45- cell fraction in mice and the CD133+ Lin-CD45- cell fraction in humans, iii) express markers of pluripotent stem cells (e.g., Oct4, Nanog, and SSEA), and iv) display a distinct morphology characterized by a high nuclear/cytoplasmic ratio and undifferentiated chromatin. Recent evidence indicates that murine VSELs are kept quiescent in adult tissues and protected from teratoma formation by epigenetic modification of imprinted genes that regulate insulin/insulin like growth factor signaling (IIS). The successful reversal of these epigenetic changes in VSELs that render them quiescent will be crucial for efficient expansion of these cells. The most recent data in vivo from our and other laboratories demonstrated that both murine and human VSELs exhibit some characteristics of long-term repopulating hematopoietic stem cells (LT-HSCs), are at the top of the hierarchy in the mesenchymal lineage, and may differentiate into organ-specific cells (e.g., cardiomyocytes). Moreover, as recently demonstrated the number of these cells positively correlates in several murine models with longevity. Finally, while murine BM-derived VSELs have been extensively characterized more work is needed to better characterize these small cells at the molecular level in humans.

  14. Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Ho, Beatrice Xuan; Pek, Nicole Min Qian; Soh, Boon-Seng

    2018-03-21

    The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo. This review serves to highlight recent advances in the 3D organoid technology for use in modeling complex hereditary diseases, cancer, host-microbe interactions, and possible use in translational and personalized medicine where organoid cultures were used to uncover diagnostic biomarkers for early disease detection via high throughput pharmaceutical screening. In addition, this review also aims to discuss the advantages and shortcomings of utilizing organoids in disease modeling. In summary, studying human diseases using hiPSC-derived organoids may better illustrate the processes involved due to similarities in the architecture and microenvironment present in an organoid, which also allows drug responses to be properly recapitulated in vitro.

  15. Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Beatrice Xuan Ho

    2018-03-01

    Full Text Available The rising interest in human induced pluripotent stem cell (hiPSC-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo. This review serves to highlight recent advances in the 3D organoid technology for use in modeling complex hereditary diseases, cancer, host–microbe interactions, and possible use in translational and personalized medicine where organoid cultures were used to uncover diagnostic biomarkers for early disease detection via high throughput pharmaceutical screening. In addition, this review also aims to discuss the advantages and shortcomings of utilizing organoids in disease modeling. In summary, studying human diseases using hiPSC-derived organoids may better illustrate the processes involved due to similarities in the architecture and microenvironment present in an organoid, which also allows drug responses to be properly recapitulated in vitro.

  16. Development of a tree shrew metabolic syndrome model and use of umbilical cord mesenchymal stem cell transplantation for treatment.

    Science.gov (United States)

    Pan, Xing-Hua; Zhu, Lu; Yao, Xiang; Liu, Ju-Fen; Li, Zi-An; Yang, Jian-Yong; Pang, Rong-Qing; Ruan, Guang-Ping

    2016-12-01

    The aim of this study was to establish a tree shrew metabolic syndrome model and demonstrate the utility of MSCs in treating metabolic syndrome. We used tree shrew umbilical cord mesenchymal stem cell (TS-UC-MSC) transplantation for the treatment of metabolic syndrome to demonstrate the clinical application of these stem cells and to provide a theoretical basis and reference methods for this treatment. Tree shrew metabolic syndrome model showed significant insulin resistance, high blood sugar, lipid metabolism disorders, and hypertension, consistent with the diagnostic criteria. TS-UC-MSC transplantation at 16 weeks significantly reduced blood sugar and lipid levels, improved insulin resistance and the regulation of insulin secretion, and reduced the expression levels of the pro-inflammatory cytokines IL-1 and IL-6 (P metabolic syndrome model and showed that MSC migrate in diseased organs and can attenuate metabolic syndrome severity in a tree shrew model.

  17. Transcriptional regulation by histone modifications: towards a theory of chromatin re-organization during stem cell differentiation

    International Nuclear Information System (INIS)

    Binder, Hans; Steiner, Lydia; Przybilla, Jens; Rohlf, Thimo; Prohaska, Sonja; Galle, Jörg

    2013-01-01

    Chromatin-related mechanisms, as e.g. histone modifications, are known to be involved in regulatory switches within the transcriptome. Only recently, mathematical models of these mechanisms have been established. So far they have not been applied to genome-wide data. We here introduce a mathematical model of transcriptional regulation by histone modifications and apply it to data of trimethylation of histone 3 at lysine 4 (H3K4me3) and 27 (H3K27me3) in mouse pluripotent and lineage-committed cells. The model describes binding of protein complexes to chromatin which are capable of reading and writing histone marks. Molecular interactions of the complexes with DNA and modified histones create a regulatory switch of transcriptional activity. The regulatory states of the switch depend on the activity of histone (de-) methylases, the strength of complex-DNA-binding and the number of nucleosomes capable of cooperatively contributing to complex-binding. Our model explains experimentally measured length distributions of modified chromatin regions. It suggests (i) that high CpG-density facilitates recruitment of the modifying complexes in embryonic stem cells and (ii) that re-organization of extended chromatin regions during lineage specification into neuronal progenitor cells requires targeted de-modification. Our approach represents a basic step towards multi-scale models of transcriptional control during development and lineage specification. (paper)

  18. Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

    Science.gov (United States)

    Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

    2015-10-01

    Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

  19. Invertebrates as model organisms for research on aging biology.

    Science.gov (United States)

    Murthy, Mahadev; Ram, Jeffrey L

    2015-01-30

    Invertebrate model systems, such as nematodes and fruit flies, have provided valuable information about the genetics and cellular biology involved in aging. However, limitations of these simple, genetically tractable organisms suggest the need for other model systems, some of them invertebrate, to facilitate further advances in the understanding of mechanisms of aging and longevity in mammals, including humans. This paper introduces 10 review articles about the use of invertebrate model systems for the study of aging by authors who participated in an 'NIA-NIH symposium on aging in invertebrate model systems' at the 2013 International Congress for Invertebrate Reproduction and Development. In contrast to the highly derived characteristics of nematodes and fruit flies as members of the superphylum Ecdysozoa, cnidarians, such as Hydra, are more 'basal' organisms that have a greater number of genetic orthologs in common with humans. Moreover, some other new model systems, such as the urochordate Botryllus schlosseri , the tunicate Ciona , and the sea urchins (Echinodermata) are members of the Deuterostomia, the same superphylum that includes all vertebrates, and thus have mechanisms that are likely to be more closely related to those occurring in humans. Additional characteristics of these new model systems, such as the recent development of new molecular and genetic tools and a more similar pattern to humans of regeneration and stem cell function suggest that these new model systems may have unique advantages for the study of mechanisms of aging and longevity.

  20. Research progress in animal models and stem cell therapy for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Han F

    2014-12-01

    Full Text Available Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the treatment of AD. We first review the advances in molecular pathogenesis and animal models of AD and then discuss recent clinical studies using small molecules and immunoglobulins to target amyloid-beta plaques for AD therapy. Finally, we discuss stem cell therapy for AD using neural stem cells, olfactory ensheathing cells, embryonic stem cells, and mesenchymal stem cell from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific induced pluripotent stem cells are proposed as a future treatment for AD. Keywords: amyloid-beta plaque, neurofibrillary tangle, neural stem cell, olfactory ensheathing cell, mesenchymal stem cell, induced pluripotent stem cell

  1. An approach to conifer stem localization and modeling in high density airborne LiDAR data

    Science.gov (United States)

    Harikumar, A.; Bovolo, F.; Bruzzone, L.

    2017-10-01

    Individual tree level inventory performed using high density multi-return airborne Light Detection and Ranging (LiDAR) systems provides both internal and external geometric details on individual tree crowns. Among them, the parameters such as, the stem location, and Diameter at Breast Height of the stem (DBH) are very relevant for accurate biomass, and forest growth estimation. However, methods that can accurately estimate these parameters along the vertical canopy are lacking in the state of the art. Thus, we propose a method to locate and model the stem by analyzing the empty volume that appears within the 3D high density LiDAR point cloud of a conifer, due to the stem. In a high LiDAR density data, the points most proximal to the stem location in the upper half of the crown are very likely due to laser reflections from the stem and/or the branch-stem junctions. By locating accurately these points, we can define the lattice of points representing branch-stem junctions and use it to model the empty volume associated to the stem location. We identify these points by using a state-of-the-art internal crown structure modelling technique that models individual conifer branches in a high density LiDAR data. Under the assumption that conifer stem can be closely modelled using a cone shape, we regression fit a geometric shape onto the lattice of branch-stem junction points. The parameters of the geometric shape are used to accurately estimate the diameter at breast height, and height of the tree. The experiments were performed on a set of hundred conifers consisting of trees from six dominant European conifer species, for which the height and the DBH were known. The results prove the method to be accurate.

  2. Precision monitoring of immunotherapies in solid organ and hematopoietic stem cell transplantation.

    Science.gov (United States)

    DiLoreto, Rose; Khush, Kiran; De Vlaminck, Iwijn

    2017-05-15

    Pharmacological immunotherapies are a key component of post-transplant therapy in solid-organ and hematopoietic stem cell transplantation. In current clinical practice, immunotherapies largely follow a one-size fits all approach, leaving a large portion of transplant recipients either over- or under-immunosuppressed, and consequently at risk of infections or immune-mediated complications. Our goal here is to review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies. We will discuss recent advances in precision measurements of pharmacological immunosuppression, measurements of the plasma and gut microbiome, strategies to monitor for allograft injury and post-transplant malignancies via circulating cell-free DNA, and comprehensive measurements of the B and T cell immune cell repertoire. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...... and 2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal......, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  5. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    International Nuclear Information System (INIS)

    Winkler, Sandra; Borkham-Kamphorst, Erawan; Stock, Peggy; Brückner, Sandra; Dollinger, Matthias; Weiskirchen, Ralf; Christ, Bruno

    2014-01-01

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH

  6. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig (Germany)

    2014-08-15

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.

  7. Arabic Language Modeling with Stem-Derived Morphemes for Automatic Speech Recognition

    Science.gov (United States)

    Heintz, Ilana

    2010-01-01

    The goal of this dissertation is to introduce a method for deriving morphemes from Arabic words using stem patterns, a feature of Arabic morphology. The motivations are three-fold: modeling with morphemes rather than words should help address the out-of-vocabulary problem; working with stem patterns should prove to be a cross-dialectally valid…

  8. Sustainability Transdisciplinary Education Model: Interface of Arts, Science, and Community (STEM)

    Science.gov (United States)

    Clark, Barbara; Button, Charles

    2011-01-01

    Purpose: The purpose of this paper is to describe the components of a sustainability transdisciplinary education model (STEM), a contemporary approach linking art, science, and community, that were developed to provide university and K-12 students, and society at large shared learning opportunities. The goals and application of the STEM curriculum…

  9. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova

    2011-08-01

    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  10. Project-matrix models of marketing organization

    Directory of Open Access Journals (Sweden)

    Gutić Dragutin

    2009-01-01

    Full Text Available Unlike theory and practice of corporation organization, in marketing organization numerous forms and contents at its disposal are not reached until this day. It can be well estimated that marketing organization today in most of our companies and in almost all its parts, noticeably gets behind corporation organization. Marketing managers have always been occupied by basic, narrow marketing activities as: sales growth, market analysis, market growth and market share, marketing research, introduction of new products, modification of products, promotion, distribution etc. They rarely found it necessary to focus a bit more to different aspects of marketing management, for example: marketing planning and marketing control, marketing organization and leading. This paper deals with aspects of project - matrix marketing organization management. Two-dimensional and more-dimensional models are presented. Among two-dimensional, these models are analyzed: Market management/products management model; Products management/management of product lifecycle phases on market model; Customers management/marketing functions management model; Demand management/marketing functions management model; Market positions management/marketing functions management model. .

  11. The Zebrafish Model Organism Database (ZFIN)

    Data.gov (United States)

    U.S. Department of Health & Human Services — ZFIN serves as the zebrafish model organism database. It aims to: a) be the community database resource for the laboratory use of zebrafish, b) develop and support...

  12. Modeling Virtual Organization Architecture with the Virtual Organization Breeding Methodology

    Science.gov (United States)

    Paszkiewicz, Zbigniew; Picard, Willy

    While Enterprise Architecture Modeling (EAM) methodologies become more and more popular, an EAM methodology tailored to the needs of virtual organizations (VO) is still to be developed. Among the most popular EAM methodologies, TOGAF has been chosen as the basis for a new EAM methodology taking into account characteristics of VOs presented in this paper. In this new methodology, referred as Virtual Organization Breeding Methodology (VOBM), concepts developed within the ECOLEAD project, e.g. the concept of Virtual Breeding Environment (VBE) or the VO creation schema, serve as fundamental elements for development of VOBM. VOBM is a generic methodology that should be adapted to a given VBE. VOBM defines the structure of VBE and VO architectures in a service-oriented environment, as well as an architecture development method for virtual organizations (ADM4VO). Finally, a preliminary set of tools and methods for VOBM is given in this paper.

  13. Complex Systems and Self-organization Modelling

    CERN Document Server

    Bertelle, Cyrille; Kadri-Dahmani, Hakima

    2009-01-01

    The concern of this book is the use of emergent computing and self-organization modelling within various applications of complex systems. The authors focus their attention both on the innovative concepts and implementations in order to model self-organizations, but also on the relevant applicative domains in which they can be used efficiently. This book is the outcome of a workshop meeting within ESM 2006 (Eurosis), held in Toulouse, France in October 2006.

  14. Pluripotent stem cells: An in vitro model for nanotoxicity assessments.

    Science.gov (United States)

    Handral, Harish K; Tong, Huei Jinn; Islam, Intekhab; Sriram, Gopu; Rosa, Vinicus; Cao, Tong

    2016-10-01

    The advent of technology has led to an established range of engineered nanoparticles that are used in diverse applications, such as cell-cell interactions, cell-material interactions, medical therapies and the target modulation of cellular processes. The exponential increase in the utilization of nanomaterials and the growing number of associated criticisms has highlighted the potential risks of nanomaterials to human health and the ecosystem. The existing in vivo and in vitro platforms show limitations, with fluctuations being observed in the results of toxicity assessments. Pluripotent stem cells (PSCs) are viable source of cells that are capable of developing into specialized cells of the human body. PSCs can be efficiently used to screen new biomaterials/drugs and are potential candidates for studying impairments of biophysical morphology at both the cellular and tissue levels during interactions with nanomaterials and for diagnosing toxicity. Three-dimensional in vitro models obtained using PSC-derived cells would provide a realistic, patient-specific platform for toxicity assessments and in drug screening applications. The current review focuses on PSCs as an alternative in vitro platform for assessing the hazardous effects of nanomaterials on health systems and highlights the importance of PSC-derived in vitro platforms. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Inactivation of Salmonella in tomato stem scars by organic acid wash and chitosan-allyl isothiocyanate coating

    Science.gov (United States)

    The objective of this study was to evaluate inactivation of inoculated Salmonella enterica on tomato stem scars exploiting integrated treatment of organic acid wash (AW) followed by chitosan-allyl isothiocyanate (CT-AIT) coating. The treatment effect on microbial loads and fruit quality during 21 d...

  16. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  17. Stem thrust prediction model for Westinghouse wedge gate valves with linkage type stem-to-disk connection

    International Nuclear Information System (INIS)

    Wang, J.K.; Sharma, V.; Kalsi, M.S.

    1996-01-01

    The Electric Power Research Institute (EPRI) conducted a comprehensive research program with the objective of providing nuclear utilities with analytical methods to predict motor operated valve (MOV) performance under design basis conditions. This paper describes the stem thrust calculation model developed for evaluating the performance of one such valve, the Westinghouse flexible wedge gate valve. These procedures account for the unique functional characteristics of this valve design. In addition, model results are compared to available flow loop and in situ test data as a basis for evaluating the performance of the valve model

  18. Stem thrust prediction model for Westinghouse wedge gate valves with linkage type stem-to-disk connection

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.K.; Sharma, V.; Kalsi, M.S. [Kalsi Engineering, Inc., Sugar Land, TX (United States)] [and others

    1996-12-01

    The Electric Power Research Institute (EPRI) conducted a comprehensive research program with the objective of providing nuclear utilities with analytical methods to predict motor operated valve (MOV) performance under design basis conditions. This paper describes the stem thrust calculation model developed for evaluating the performance of one such valve, the Westinghouse flexible wedge gate valve. These procedures account for the unique functional characteristics of this valve design. In addition, model results are compared to available flow loop and in situ test data as a basis for evaluating the performance of the valve model.

  19. Role model and prototype matching: Upper-secondary school students’ meetings with tertiary STEM students

    DEFF Research Database (Denmark)

    Lykkegaard, Eva; Ulriksen, Lars

    2016-01-01

    concerning STEM students and attending university. The regular self-to-prototype matching process was shown in real-life role-models meetings to be extended to a more complex three-way matching process between students’ self-perceptions, prototype images and situation-specific conceptions of role models......Previous research has found that young people’s prototypes of science students and scientists affect their inclination to choose tertiary STEM programs. Consequently, many recruitment initiatives include role models to challenge these prototypes. The present study followed 15 STEM-oriented upper......-secondary school students from university-distant backgrounds during and after their participation in an 18-months long university-based recruitment and outreach project involving tertiary STEM students as role models. The analysis focusses on how the students’ meetings with the role models affected their thoughts...

  20. In vitro functional gut-like organ formation from mouse embryonic stem cells.

    Science.gov (United States)

    Yamada, Takatsugu; Yoshikawa, Masahide; Takaki, Miyako; Torihashi, Shigeko; Kato, Yoko; Nakajima, Yoshiyuki; Ishizaka, Shigeaki; Tsunoda, Yukio

    2002-01-01

    Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages in vitro. We have recently found that ES cells can give rise to a functional gut-like unit, which forms a three-dimensional dome-like structure with lumen and exhibits mechanical activity, such as spontaneous contraction and peristalsis. The aim of the present study was to investigate the electrophysiological and morphological properties of ES cell-derived contracting clusters. Electrical activity was examined by an extracellular recording. Morphology and cellular components were investigated by immunohistochemistry and electron microscopy. Clusters with rhythmic contractions displayed electrical slow waves at a regular rhythm, and clusters with highly coordinated peristalsis showed regular slow waves and spontaneous spike action potentials. Immunoreactivity for c-Kit, a marker of interstitial cells of Cajal (ICC), was observed in dense network structures. Neuronal marker PGP9.5 immunoreactivity was observed only in clusters with peristalsis. The topographical structure of the wall was organized by an inner epithelial layer and outer smooth muscle layer. The smooth muscle layer was provided with an ICC network and innervated with enteric neurons. ES cells can differentiate into a functional gut-like organ in vitro that exhibits physiological and morphological properties characteristic of the gastrointestinal (GI) tract. This ES cell-derived gut provides a powerful tool for studying GI motility and gut development in vitro, and has potential for elucidating and treating a variety of motility disorders.

  1. Generation of mesenchymal stem cells as a medicinal product in organ transplantation.

    Science.gov (United States)

    Verbeek, Richard

    2013-02-01

    Mesenchymal stem cells (MSCs) are emerging as an alternative treatment in solid-organ transplantation. The use of MSCs as a therapeutic product requires the translation of basic research protocols into a production process under good manufacturing practice (GMP) to obtain a safe product of high quality. This requires a different mindset from the academic setting of changing protocols into a well defined, controlled and documented process. This review describes some of the challenges faced by culturing MSCs as a medicinal product. Clinical-grade MSCs are used in the clinical trials and proved to be safe as a medicinal product. Because of the differences in the type of MSCs and in the production process, clinical outcome is not always comparable. New standardized methods in the culture condition such as the use of alternatives for fetal bovine serum (FBS), standardized plating densities or the use of bioreactors may further standardize the production process. To generate MSCs as a medicinal product in organ transplantation, regulation requires that MSCs have to be generated under GMP. During the whole production process, all critical steps should be known and described. Further steps should be taken to optimize and standardize the production process.

  2. The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

    OpenAIRE

    Muller-Sieburg, C.E.; Sieburg, H.B.

    2006-01-01

    Hematopoietic stem cells (HSC) show heterogeneous behavior even when isolated as phenotypically homogeneous populations. The cellular and molecular mechanisms that control the generation of diversity (GOD) in the HSC compartment are not well understood, but have been the focus of much debate. There is increasing evidence that the most important HSC functions, self-renewal and differentiation, are epigenetically preprogrammed and therefore predictable. Indeed, recent data show that the adult H...

  3. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

    Energy Technology Data Exchange (ETDEWEB)

    Francois, S

    2006-01-15

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  4. Precise and long-term tracking of adipose-derived stem cells and their regenerative capacity via superb bright and stable organic nanodots.

    Science.gov (United States)

    Ding, Dan; Mao, Duo; Li, Kai; Wang, Xiaomin; Qin, Wei; Liu, Rongrong; Chiam, David Shunzhong; Tomczak, Nikodem; Yang, Zhimou; Tang, Ben Zhong; Kong, Deling; Liu, Bin

    2014-12-23

    Monitoring and understanding long-term fate and regenerative therapy of administrated stem cells in vivo is of great importance. Herein we report organic nanodots with aggregation-induced emission characteristics (AIE dots) for long-term tracking of adipose-derived stem cells (ADSCs) and their regenerative capacity in living mice. The AIE dots possess high fluorescence (with a high quantum yield of 25±1%), excellent biological and photophysical stabilities, low in vivo toxicity, and superb retention in living ADSCs with negligible interference on their pluripotency and secretome. These AIE dots also exhibit superior in vitro cell tracking capability compared to the most popular commercial cell trackers, PKH26 and Qtracker 655. In vivo quantitative studies with bioluminescence and GFP labeling as the controls reveal that the AIE dots can precisely and quantitatively report the fate of ADSCs and their regenerative capacity for 42 days in an ischemic hind limb bearing mouse model.

  5. The free-living flatworm Macrostomum lignano: a new model organism for ageing research.

    Science.gov (United States)

    Mouton, Stijn; Willems, Maxime; Braeckman, Bart P; Egger, Bernhard; Ladurner, Peter; Schärer, Lukas; Borgonie, Gaetan

    2009-04-01

    To study the several elements and causes of ageing, diverse model organisms and methodologies are required. The most frequently used models are Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster and rodents. All have their advantages and disadvantages and allow studying particular aspects of the ageing process. During the last few years, several ageing studies focussed on stem cells and their role in tissue homeostasis. Here we present a new model organism which can study this relation where other model systems fail. The flatworm Macrostomum lignano possesses a dynamic population of likely totipotent somatic stem cells known as neoblasts. Several characteristics qualify M. lignano as a suitable model system for ageing studies in general and more specifically for gaining more insight in the causal relation between stem cells, ageing and rejuvenation. In this review, we will briefly describe the species and its life history, and discuss the role of its stem cells in ageing and rejuvenation. We also give an overview of the available experimental tools that allow a multidisciplinary approach for studying ageing in M. lignano.

  6. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.

    Directory of Open Access Journals (Sweden)

    Andrea Sottoriva

    2011-05-01

    Full Text Available The cancer stem cell (CSC concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.

  7. The U.S. STEM Undergraduate Model: Applying System Dynamics to Help Meet President Obama's Goals for One Million STEM Graduates and the U.S. Navy's Civilian STEM Workforce Needs

    Science.gov (United States)

    Business-Higher Education Forum, 2013

    2013-01-01

    This report shows how insights gained from system dynamics modeling and the U.S. STEM Undergraduate Model® can help inform the Navy's strategy to grow a robust civilian workforce that is strongly invested with Navy-relevant STEM skills and ready to contribute to the next generation of Naval innovation. This work positions the Navy to serve a…

  8. Stem breakage of salt marsh vegetation under wave forcing: A field and model study

    Science.gov (United States)

    Vuik, Vincent; Suh Heo, Hannah Y.; Zhu, Zhenchang; Borsje, Bas W.; Jonkman, Sebastiaan N.

    2018-01-01

    One of the services provided by coastal ecosystems is wave attenuation by vegetation, and subsequent reduction of wave loads on flood defense structures. Therefore, stability of vegetation under wave forcing is an important factor to consider. This paper presents a model which determines the wave load that plant stems can withstand before they break or fold. This occurs when wave-induced bending stresses exceed the flexural strength of stems. Flexural strength was determined by means of three-point-bending tests, which were carried out for two common salt marsh species: Spartina anglica (common cord-grass) and Scirpus maritimus (sea club-rush), at different stages in the seasonal cycle. Plant stability is expressed in terms of a critical orbital velocity, which combines factors that contribute to stability: high flexural strength, large stem diameter, low vegetation height, high flexibility and a low drag coefficient. In order to include stem breakage in the computation of wave attenuation by vegetation, the stem breakage model was implemented in a wave energy balance. A model parameter was calibrated so that the predicted stem breakage corresponded with the wave-induced loss of biomass that occurred in the field. The stability of Spartina is significantly higher than that of Scirpus, because of its higher strength, shorter stems, and greater flexibility. The model is validated by applying wave flume tests of Elymus athericus (sea couch), which produced reasonable results with regards to the threshold of folding and overall stem breakage percentage, despite the high flexibility of this species. Application of the stem breakage model will lead to a more realistic assessment of the role of vegetation for coastal protection.

  9. Human embryonic stem cells as models for aneuploid chromosomal syndromes.

    Science.gov (United States)

    Biancotti, Juan-Carlos; Narwani, Kavita; Buehler, Nicole; Mandefro, Berhan; Golan-Lev, Tamar; Yanuka, Ofra; Clark, Amander; Hill, David; Benvenisty, Nissim; Lavon, Neta

    2010-09-01

    Syndromes caused by chromosomal aneuploidies are widely recognized genetic disorders in humans and often lead to spontaneous miscarriage. Preimplantation genetic screening is used to detect chromosomal aneuploidies in early embryos. Our aim was to derive aneuploid human embryonic stem cell (hESC) lines that may serve as models for human syndromes caused by aneuploidies. We have established 25 hESC lines from blastocysts diagnosed as aneuploid on day 3 of their in vitro development. The hESC lines exhibited morphology and expressed markers typical of hESCs. They demonstrated long-term proliferation capacity and pluripotent differentiation. Karyotype analysis revealed that two-third of the cell lines carry a normal euploid karyotype, while one-third remained aneuploid throughout the derivation, resulting in eight hESC lines carrying either trisomy 13 (Patau syndrome), 16, 17, 21 (Down syndrome), X (Triple X syndrome), or monosomy X (Turner syndrome). On the basis of the level of single nucleotide polymorphism heterozygosity in the aneuploid chromosomes, we determined whether the aneuploidy originated from meiotic or mitotic chromosomal nondisjunction. Gene expression profiles of the trisomic cell lines suggested that all three chromosomes are actively transcribed. Our analysis allowed us to determine which tissues are most affected by the presence of a third copy of either chromosome 13, 16, 17 or 21 and highlighted the effects of trisomies on embryonic development. The results presented here suggest that aneuploid embryos can serve as an alternative source for either normal euploid or aneuploid hESC lines, which represent an invaluable tool to study developmental aspects of chromosomal abnormalities in humans.

  10. Cell-based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells.

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-Gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W

    2014-11-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver, or brain. Genomic, proteomic, and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of promitotic, antiapoptotic, antiinflammatory, and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, the authors review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. (ANESTHESIOLOGY 2014; 121:1099-121).

  11. Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

    Directory of Open Access Journals (Sweden)

    Nikolce Gjorevski

    2017-01-01

    Full Text Available Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

  12. The conceptual model of organization social responsibility

    OpenAIRE

    LUO, Lan; WEI, Jingfu

    2014-01-01

    With the developing of the research of CSR, people more and more deeply noticethat the corporate should take responsibility. Whether other organizations besides corporatesshould not take responsibilities beyond their field? This paper puts forward theconcept of organization social responsibility on the basis of the concept of corporate socialresponsibility and other theories. And the conceptual models are built based on theconception, introducing the OSR from three angles: the types of organi...

  13. A Model of Factors Contributing to STEM Learning and Career Orientation

    Science.gov (United States)

    Nugent, Gwen; Barker, Bradley; Welch, Greg; Grandgenett, Neal; Wu, ChaoRong; Nelson, Carl

    2015-05-01

    The purpose of this research was to develop and test a model of factors contributing to science, technology, engineering, and mathematics (STEM) learning and career orientation, examining the complex paths and relationships among social, motivational, and instructional factors underlying these outcomes for middle school youth. Social cognitive career theory provided the foundation for the research because of its emphasis on explaining mechanisms which influence both career orientations and academic performance. Key constructs investigated were youth STEM interest, self-efficacy, and career outcome expectancy (consequences of particular actions). The study also investigated the effects of prior knowledge, use of problem-solving learning strategies, and the support and influence of informal educators, family members, and peers. A structural equation model was developed, and structural equation modeling procedures were used to test proposed relationships between these constructs. Results showed that educators, peers, and family-influenced youth STEM interest, which in turn predicted their STEM self-efficacy and career outcome expectancy. STEM career orientation was fostered by youth-expected outcomes for such careers. Results suggest that students' pathways to STEM careers and learning can be largely explained by these constructs, and underscore the importance of youth STEM interest.

  14. Immunosuppressive and remodelling properties of mesenchymal stem cells in a model of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Patricia Semedo

    2009-12-01

    Full Text Available Objective: To investigate the role of mesenchymal stem cells in fibrogenesis using a model of chronic renal insufficiency. Methods: Mesenchymal stem cells  were obtained from tibias and femurs of Wistar-EPM rats. After three to five passages, the cells were submitted to phenotypic analyses and differentiation. Wistar rats were submitted to the 5/6 nephrectomy model, and 2.105 mesenchymal stem cells  were administered intravenously to each rat every two weeks until the eighth week. Rresults: Sex-determining region Y was observed in female rats treated with stem cells. Serum and urine analyses showed improvement of functional parameters in mesenchymal stem cells treated animals, such as creatinine, serum urea, and proteinuria. Moreover, hemocrit analysis showed improvement of anemia in mesenchymal stem cells treated animals. Masson’s Trichromium and Picrosirius Red staining demonstrated reduced levels of fibrosis in mesenchymal stem cells treated in animals. These results were corroborated by reduced vimentin, collagen I, TGFβ, FSP-1, MCP-1 and Smad3 mRNA expression. Renal IL-6 and TNFα mRNA expression levels were significantly decreased after mesenchymal stem cells treatment, while IL-4 and IL-10 expression were increased. Serum expression of IL-1α, IL-1β, IL-6, IFN-γ, TNF-α, and IL-10 was decreased in mesenchymal cell-treated animals. Cconclusions: Altogether, these results suggest that mesenchymal stem cells therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal lesion. The immunosuppresive and remodeling properties of the mesenchymal stem cells  may be involved in the improved fibrotic outcome.

  15. Dual chamber stent prevents organ malperfusion in a model of donation after cardiac death.

    Science.gov (United States)

    Tillman, Bryan W; Chun, Youngjae; Cho, Sung Kwon; Chen, Yanfei; Liang, Nathan; Maul, Timothy; Demetris, Anthony; Gu, Xinzhu; Wagner, William R; Tevar, Amit D

    2016-10-01

    The paradigm for donation after cardiac death subjects donor organs to ischemic injury. A dual-chamber organ perfusion stent would maintain organ perfusion without affecting natural cardiac death. A center lumen allows uninterrupted cardiac blood flow, while an external chamber delivers oxygenated blood to the visceral vessels. A prototype organ perfusion stent was constructed from commercial stents. In a porcine model, the organ perfusion stent was deployed, followed by a simulated agonal period. Oxygenated blood perfused the external stent chamber. Organ perfusion was compared between controls (n = 3) and organ perfusion stent (n = 6). Finally, a custom, nitinol, dual chamber organ perfusion stent was fabricated using a retrievable "petal and stem" design. Endovascular organ perfusion stent deployment achieved visceral isolation without adverse impact on cardiac parameters. Visceral oxygen delivery was 4.8-fold greater compared with controls. During the agonal period, organs in organ perfusion stent-treated animals appeared well perfused in contrast with the malperfused controls. A custom nitinol and polyurethane organ perfusion stent was recaptured easily with simple sheath advancement. An organ perfusion stent maintained organ perfusion during the agonal phase in a porcine model of donation after cardiac death organ donation without adversely affecting cardiac function. Ultimately, the custom retrievable design of this study may help resolve the critical shortage of donor organs for transplant. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

    Science.gov (United States)

    Qu, Bo; Xin, Guo-Rong; Zhao, Li-Xia; Xing, Hui; Lian, Li-Ying; Jiang, Hai-Yan; Tong, Jia-Zhao; Wang, Bei-Bei; Jin, Shi-Zhu

    2014-01-01

    The gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD). BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

  17. Diagnosis and treatment of fungal infections in allogeneic stem cell and solid organ transplant recipients.

    Science.gov (United States)

    Vehreschild, Jörg J; Rüping, Maria J G T; Steinbach, Angela; Cornely, Oliver A

    2010-01-01

    Invasive fungal diseases (IFD) are severe complications in patients receiving immunosuppression after solid organ or allogeneic stem cell transplantation. Extensive study has been conducted on therapeutic strategies for IFD in neutropenic patients, mostly those with hematological malignancy. There is an ongoing discussion on whether these studies may be applied to transplant patients as well. We have reviewed relevant literature on transplantation and clinical mycology of the last 20 years and selected articles relevant for today's treatment decisions. This article reports on the epidemiology of IFD in transplant recipients and current antifungal drugs in the context of tansplantation medicine. For invasive aspergillosis and invasive candidiasis, we give a detailed report of current clinical evidence. This review is intended as a quick-start for clinicians and other care providers new to transplant care and as an update for experienced transplant physicians. In a field in which evidence is scarce and conflicting, we provide evidence-based strategies for diagnosing and treating the most relevant IFD in transplant recipients. Physicians treating transplant patients should maintain a high level of awareness towards IFD. They should know the local epidemiology of IFD to make the optimal decision between current diagnostic and therapeutic strategies. Prophylaxis or early treatment should be considered given the high mortality of IFD.

  18. Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review

    Science.gov (United States)

    L'Huillier, Arnaud G; Kumar, Deepali

    2015-01-01

    The Solid Organ Transplantation (SOT) and Haematopoietic Stem Cell Transplantation (HSCT) population is continuously increasing as a result of broader indications for transplant and improved survival. Infectious diseases, including vaccine-preventable diseases, are a significant threat for this population, primarily after but also prior to transplantation. As a consequence, clinicians must ensure that patients are optimally immunized before transplantation, to provide the best protection during the early post-transplantation period, when immunosuppression is the strongest and vaccine responses are poor. After 3–6 months, inactivated vaccines immunization can be resumed. By contrast, live-attenuated vaccines are lifelong contraindicated in SOT patients, but can be considered in HSCT patients at least 2 years after transplantation, if there is no immunosuppression or graft-versus-host-disease. However, because of the advantages of live-attenuated over inactivated vaccines - and also sometimes the absence of an inactivated alternative - an increasing number of prospective studies on live vaccine immunization after transplantation are performed and give new insights about safety and immunogenicity in this population. PMID:26291740

  19. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  20. Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

    Directory of Open Access Journals (Sweden)

    Sriram Chandrasekaran

    2017-12-01

    Full Text Available Summary: Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates. The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells. Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive and primed cells. Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate. : Chandrasekaran et al. use computational modeling, metabolomics, and metabolic inhibitors to discover metabolic differences between various pluripotent stem cell states and infer their impact on stem cell fate decisions. Keywords: systems biology, stem cell biology, metabolism, genome-scale modeling, pluripotency, histone methylation, naive (ground state, primed state, cell fate, metabolic network

  1. A Comprehensive Review of Immunization Practices in Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients.

    Science.gov (United States)

    Chong, Pearlie P; Avery, Robin K

    2017-08-01

    Vaccine-preventable diseases, especially influenza, varicella, herpes zoster, and invasive pneumococcal infections, continue to lead to significant morbidity and mortality in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. We highlight guideline recommendations for the use of key vaccines in SOT and HSCT recipients and to review the latest evidence and developments in the field. Physicians should vaccinate individuals with end-stage organ disease, as vaccine seroresponse rates are higher pretransplantation. Most live attenuated vaccines continue to be contraindicated post-transplantation, but there are emerging safety profile and efficacy data to support the use of specific live attenuated vaccines, such as measles, mumps, and rubella in pediatric liver or kidney transplant recipients who are on low-level maintenance immunosuppression and without recent history of allograft rejection. An inactivated subunit varicella zoster virus vaccine is currently awaiting US Food and Drug Administration approval. While we await the safety profile and efficacy data of this subunit vaccine in transplant recipients, it will likely benefit immunocompromised individuals, including transplant recipients, because the live attenuated herpes zoster vaccine is currently contraindicated in transplant recipients and transplantation candidates receiving immunosuppression. There is currently no evidence that vaccines lead to allograft rejection in SOT recipients. Household contacts of SOT and HSCT recipients should be vaccinated per the Advisory Committee on Immunization Practices schedule and recommendations. Immunizations remain underutilized in transplantation patients. Although efficacy of vaccines in SOT and HSCT may be suboptimal, partial protection is preferred over no protection. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  2. Stem cells regenerative properties on new rat spinal fusion model

    Czech Academy of Sciences Publication Activity Database

    Klíma, K.; Vaněček, Václav; Kohout, A.; Jiroušek, Ondřej; Foltán, R.; Štulík, J.; Machoň, V.; Pavlíková, G.; Jendelová, Pavla; Syková, Eva; Šedý, Jiří

    2015-01-01

    Roč. 64, č. 1 (2015), s. 119-128 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT13477; GA ČR(CZ) GAP304/10/0320 Institutional support: RVO:67985823 ; RVO:68378297 ; RVO:68378041 Keywords : mesenchymal stem cells * bone graft substitute * spinal fusion Subject RIV: FH - Neurology Impact factor: 1.643, year: 2015

  3. Development and validation of stem volume models for Pinus kesiya ...

    African Journals Online (AJOL)

    Stem volume equations (overbark) were developed, using established volume equation forms, and validated using a subset of the data collected for Pinus kesiya in Benguet province, Philippines. A total of 481 trees from Pinus kesiya stands in Benguet were measured through non-destructive sampling. The data set was ...

  4. Stem biomass and volume models of selected tropical tree species ...

    African Journals Online (AJOL)

    Estimating tree volume and biomass constitutes an essential part of the forest resources assessment and the evaluation of the climate change mitigation potential of forests through biomass accumulation and carbon sequestration. This research article provides stem volume and biomass equations applicable to five tree ...

  5. Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

    Science.gov (United States)

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

    Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

  6. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem

  7. Numerical Model of Streaming DEP for Stem Cell Sorting

    Directory of Open Access Journals (Sweden)

    Rucha Natu

    2016-11-01

    Full Text Available Neural stem cells are of special interest due to their potential in neurogenesis to treat spinal cord injuries and other nervous disorders. Flow cytometry, a common technique used for cell sorting, is limited due to the lack of antigens and labels that are specific enough to stem cells of interest. Dielectrophoresis (DEP is a label-free separation technique that has been recently demonstrated for the enrichment of neural stem/progenitor cells. Here we use numerical simulation to investigate the use of streaming DEP for the continuous sorting of neural stem/progenitor cells. Streaming DEP refers to the focusing of cells into streams by equilibrating the dielectrophoresis and drag forces acting on them. The width of the stream should be maximized to increase throughput while the separation between streams must be widened to increase efficiency during retrieval. The aim is to understand how device geometry and experimental variables affect the throughput and efficiency of continuous sorting of SC27 stem cells, a neurogenic progenitor, from SC23 cells, an astrogenic progenitor. We define efficiency as the ratio between the number of SC27 cells over total number of cells retrieved in the streams, and throughput as the number of SC27 cells retrieved in the streams compared to their total number introduced to the device. The use of cylindrical electrodes as tall as the channel yields streams featuring >98% of SC27 cells and width up to 80 µm when using a flow rate of 10 µL/min and sample cell concentration up to 105 cells/mL.

  8. COMPUTER MODEL FOR ORGANIC FERTILIZER EVALUATION

    OpenAIRE

    Lončarić, Zdenko; Vukobratović, Marija; Ragaly, Peter; Filep, Tibor; Popović, Brigita; Karalić, Krunoslav; Vukobratović, Želimir

    2009-01-01

    Evaluation of manures, composts and growing media quality should include enough properties to enable an optimal use from productivity and environmental points of view. The aim of this paper is to describe basic structure of organic fertilizer (and growing media) evaluation model to present the model example by comparison of different manures as well as example of using plant growth experiment for calculating impact of pH and EC of growing media on lettuce plant growth. The basic structure of ...

  9. Resveratrol and Lifespan in Model Organisms.

    Science.gov (United States)

    Pallauf, Kathrin; Rimbach, Gerald; Rupp, Petra Maria; Chin, Dawn; Wolf, Insa M A

    2016-01-01

    Resveratrol may possess life-prolonging and health-benefitting properties, some of which may resemble the effect of caloric restriction (CR). CR appears to prolong the lifespan of model organisms in some studies and may benefit human health. However, for humans, restricting food intake for an extended period of time seems impracticable and substances imitating the beneficial effects of CR without having to reduce food intake could improve health in an aging and overweight population. We have reviewed the literature studying the influence of resveratrol on the lifespan of model organisms including yeast, flies, worms, and rodents. We summarize the in vivo findings, describe modulations of molecular targets and gene expression observed in vivo and in vitro, and discuss how these changes may contribute to lifespan extension. Data from clinical studies are summarized to provide an insight about the potential of resveratrol supplementation in humans. Resveratrol supplementation has been shown to prolong lifespan in approximately 60% of the studies conducted in model organisms. However, current literature is contradictory, indicating that the lifespan effects of resveratrol vary strongly depending on the model organism. While worms and killifish seemed very responsive to resveratrol, resveratrol failed to affect lifespan in the majority of the studies conducted in flies and mice. Furthermore, factors such as dose, gender, genetic background and diet composition may contribute to the high variance in the observed effects. It remains inconclusive whether resveratrol is indeed a CR mimetic and possesses life-prolonging properties. The limited bioavailability of resveratrol may further impede its potential effects.

  10. Integrated modelling of two xenobiotic organic compounds

    DEFF Research Database (Denmark)

    Lindblom, Erik Ulfson; Gernaey, K.V.; Henze, Mogens

    2006-01-01

    This paper presents a dynamic mathematical model that describes the fate and transport of two selected xenobiotic organic compounds (XOCs) in a simplified representation. of an integrated urban wastewater system. A simulation study, where the xenobiotics bisphenol A and pyrene are used as reference...

  11. A STRATEGIC MANAGEMENT MODEL FOR SERVICE ORGANIZATIONS

    OpenAIRE

    Andreea ZAMFIR

    2013-01-01

    This paper provides a knowledge-based strategic management of services model, with a view to emphasise an approach to gaining competitive advantage through knowledge, people and networking. The long-term evolution of the service organization is associated with the way in which the strategic management is practised.

  12. Mesenchymal stem cells support growth and organization of host-liver colorectal-tumor organoids and possibly resistance to chemotherapy.

    Science.gov (United States)

    Devarasetty, Mahesh; Wang, Edina; Soker, Shay; Skardal, Aleksander

    2017-06-07

    Despite having yielded extensive breakthroughs in cancer research, traditional 2D cell cultures have limitations in studying cancer progression and metastasis and screening therapeutic candidates. 3D systems can allow cells to grow, migrate, and interact with each other and the surrounding matrix, resulting in more realistic constructs. Furthermore, interactions between host tissue and developing tumors influence the susceptibility of tumors to drug treatments. Host-liver colorectal-tumor spheroids composed of primary human hepatocytes, mesenchymal stem cells (MSC) and colon carcinoma HCT116 cells were created in simulated microgravity rotating wall vessel (RWV) bioreactors. The cells were seeded on hyaluronic acid-based microcarriers, loaded with liver-specific growth factors and ECM components. Only in the presence of MSC, large tumor foci rapidly formed inside the spheroids and increased in size steadily over time, while not greatly impacting albumin secretion from hepatocytes. The presence of MSC appeared to drive self-organization and formation of a stroma-like tissue surrounding the tumor foci and hepatocytes. Exposure to a commonly used chemotherapeutic 5-FU showed a dose-dependent cytotoxicity. However, if tumor organoids were allowed to mature in the RWV, they were less sensitive to the drug treatment. These data demonstrate the potential utility of liver tumor organoids for cancer progression and drug response modeling.

  13. Modeling of Organic Effects on Aerosols Growth

    Science.gov (United States)

    Caboussat, A.; Amundson, N. R.; He, J.; Seinfeld, J. H.

    2006-05-01

    Over the last two decades, a series of modules has been developed in the atmospheric modeling community to predict the phase transition, multistage growth phenomena, crystallization and evaporation of inorganic aerosols. In the same time, the water interactions of particles containing organic constituents have been recognized as an important factor for aerosol activation and cloud formation. However, the research on hygroscopicity of organic-containing aerosols, motivated by the organic effect on aerosol growth and activation, has gathered much less attention. We present here a new model (UHAERO), that is both efficient and rigorously computes phase separation and liquid-liquid equilibrium for organic particles, as well as the dynamics partitioning between gas and particulate phases, with emphasis on the role of water vapor in the gas-liquid partitioning. The model does not rely on any a priori specification of the phases present in certain atmospheric conditions. The determination of the thermodynamic equilibrium is based on the minimization of the Gibbs free energy. The mass transfer between the particle and the bulk gas phase is dynamically driven by the difference between bulk gas pressure and the gas pressure at the surface of a particle. The multicomponent phase equilibrium for a closed organic aerosol system at constant temperature and pressure and for specified feeds is the solution to the liquid-liquid equilibrium problem arising from the constrained minimization of the Gibbs free energy. A geometrical concept of phase simplex (phase separation) is introduced to characterize the thermodynamic equilibrium. The computation of the mass fluxes is achieved by coupling the thermodynamics of the organic aerosol particle and the determination of the mass fluxes. Numerical results show the efficiency of the model, which make it suitable for insertion in global three- dimensional air quality models. The Gibbs free energy is modeled by the UNIFAC model to illustrate

  14. Growth dynamics and cytoskeleton organization during stem maturation and gravity-induced stem bending in Zea mays L

    Science.gov (United States)

    Collings, D. A.; Winter, H.; Wyatt, S. E.; Allen, N. S.; Davies, E. (Principal Investigator)

    1998-01-01

    Characterization of gravitropic bending in the maize stem pulvinus, a tissue that functions specifically in gravity responses, demonstrates that the pulvinus is an ideal system for studying gravitropism. Gravistimulation during the second of three developmental phases of the pulvinus induces a gradient of cell elongation across the non-growing cells of the pulvinus, with the most elongation occurring on the lower side. This cell elongation is spatially and temporally separated from normal internodal cell elongation. The three characterized growth phases in the pulvinus correspond closely to a specialized developmental sequence in which structural features typical of cells not fully matured are retained while cell maturation occurs in surrounding internodal and nodal tissue. For example, the lignification of supporting tissue and rearrangement of transverse microtubules to oblique that occur in the internode when cell elongation ceases are delayed for up to 10 d in the adjacent cells of the pulvinus, and only occurs as a pulvinus loses its capacity to respond to gravistimulation. Gravistimulation does not modify this developmental sequence. Neither wall lignification nor rearrangement of transverse microtubules occurs in the rapidly elongating lower side or non-responsive upper side of the pulvinus until the pulvinus loses the capacity to bend further. Gravistimulation does, however, lead to the formation of putative pit fields within the expanding cells of the pulvinus.

  15. Emergent organization in a model market

    Science.gov (United States)

    Yadav, Avinash Chand; Manchanda, Kaustubh; Ramaswamy, Ramakrishna

    2017-09-01

    We study the collective behaviour of interacting agents in a simple model of market economics that was originally introduced by Nørrelykke and Bak. A general theoretical framework for interacting traders on an arbitrary network is presented, with the interaction consisting of buying (namely consumption) and selling (namely production) of commodities. Extremal dynamics is introduced by having the agent with least profit in the market readjust prices, causing the market to self-organize. In addition to examining this model market on regular lattices in two-dimensions, we also study the cases of random complex networks both with and without community structures. Fluctuations in an activity signal exhibit properties that are characteristic of avalanches observed in models of self-organized criticality, and these can be described by power-law distributions when the system is in the critical state.

  16. Biophysical Modeling of Respiratory Organ Motion

    Science.gov (United States)

    Werner, René

    Methods to estimate respiratory organ motion can be divided into two groups: biophysical modeling and image registration. In image registration, motion fields are directly extracted from 4D ({D}+{t}) image sequences, often without concerning knowledge about anatomy and physiology in detail. In contrast, biophysical approaches aim at identification of anatomical and physiological aspects of breathing dynamics that are to be modeled. In the context of radiation therapy, biophysical modeling of respiratory organ motion commonly refers to the framework of continuum mechanics and elasticity theory, respectively. Underlying ideas and corresponding boundary value problems of those approaches are described in this chapter, along with a brief comparison to image registration-based motion field estimation.

  17. Methods in Molecular Biology: Germline Stem Cells | Center for Cancer Research

    Science.gov (United States)

    The protocols in Germline Stem Cells are intended to present selected genetic, molecular, and cellular techniques used in germline stem cell research. The book is divided into two parts. Part I covers germline stem cell identification and regulation in model organisms. Part II covers current techniques used in in vitro culture and applications of germline stem cells.

  18. Dynamics of prostate cancer stem cells with diffusion and organism response.

    Science.gov (United States)

    Quinn, Terrance; Sinkala, Zachariah

    2009-04-01

    We develop a systems based model for prostate cancer, as a sub-system of the organism. We accomplish this in two stages. We first start with a general ODE that includes organism response terms. Then, to account for normally observed spatial diffusion of cell populations, the ODE is extended to a PDE that includes spatial terms. Numerical solutions of the full PDE are provided, and are indicative of traveling wave fronts. This motivates the use of a well known transformation to derive a canonically related (non-linear) system of ODEs for traveling wave solutions. For biological feasibility, we show that the non-negative cone for the traveling wave system is time invariant. We also prove that the traveling waves have a unique global attractor. Biologically, the global attractor would be the limit for the avascular tumor growth. We conclude with comments on clinical implications of the model.

  19. [Nosocomial infection in patients receiving a solid organ transplant or haematopoietic stem cell transplant].

    Science.gov (United States)

    Moreno Camacho, Asunción; Ruiz Camps, Isabel

    2014-01-01

    Bacterial infections are the most common infections in solid organ transplant recipients. These infections occur mainly in the first month after transplantation and are hospital-acquired. Nosocomial infections cause significant morbidity and are the most common cause of mortality in this early period of transplantation. These infections are caused by multi-drug resistant (MDR) microorganisms, mainly Gram-negative enterobacteria, non-fermentative Gram-negative bacilli, enterococci, and staphylococci. The patients at risk of developing nosocomial bacterial infections are those previously colonized with MDR bacteria while on the transplant waiting list. Intravascular catheters, the urinary tract, the lungs, and surgical wounds are the most frequent sources of infection. Preventive measures are the same as those applied in non-immunocompromised, hospitalized patients except in patients at high risk for developing fungal infection. These patients need antifungal therapy during their hospitalization, and for preventing some bacterial infections in the early transplant period, patients need vaccinations on the waiting list according to the current recommendations. Although morbidity and mortality related to infectious diseases have decreased during the last few years in haematopoietic stem cell transplant recipients, they are still one of the most important complications in this population. Furthermore, as occurs in the general population, the incidence of nosocomial infections has increased during the different phases of transplantation. It is difficult to establish general preventive measures in these patients, as there are many risk factors conditioning these infections. Firstly, they undergo multiple antibiotic treatments and interventions; secondly, there is a wide variability in the degree of neutropenia and immunosuppression among patients, and finally they combine hospital and home stay during the transplant process. However, some simple measures could be

  20. [Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice].

    Science.gov (United States)

    Chen, Ling-Zhen; Yin, Song-Mei; Zhang, Xiao-Ling; Chen, Jia-Yu; Wei, Bo-Xiong; Zhan, Yu; Yu, Wei; Wu, Jin-Ming; Qu, Jia; Guo, Zi-Kuan

    2012-12-01

    The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co γ-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells.

  1. Characterization of in vitro gutlike organ formed from mouse embryonic stem cells.

    Science.gov (United States)

    Ishikawa, Tadao; Nakayama, Shinsuke; Nakagawa, Tadashi; Horiguchi, Kazuhide; Misawa, Hiromi; Kadowaki, Makoto; Nakao, Akimasa; Inoue, Soichiro; Komuro, Terumasa; Takaki, Miyako

    2004-06-01

    Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca(2+) concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.

  2. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  3. Mesenchymal stem cells as a therapeutic tool in tissue and organ regeneration

    Directory of Open Access Journals (Sweden)

    Anna Bajek

    2011-01-01

    Full Text Available Tissue engineering is an interdisciplinary field that offers new opportunities for regeneration of diseased and damaged tissue with the use of many different cell types,including adult stem cells. In tissue engineering and regenerative medicine the most popular are mesenchymal stem cells (MSCs isolated from bone marrow. Bone marrow mesenchymal stem cells are a potential source of progenitor cells for osteoblasts, chondroblasts, adipocytes, skeletal muscles and cardiomyocytes. It has also been shown that these cells can differentiate into ecto- and endodermal cells, e.g. neuronal cells, glial cells, keratinocytes and hepatocytes. The availability of autologous MSCs, their proliferative potential and multilineage differentiation capacity make them an excellent tool for tissue engineering and regenerative medicine. The aim of this publication is to present characteristic and biological properties of mesenchymal stem cells isolated from bone marrow.

  4. Current challenges for the targeted delivery and molecular imaging of stem cells in animal models.

    Science.gov (United States)

    Momeni, Arezoo; Neelamegham, Sriram; Parashurama, Natesh

    2017-07-04

    In contrast to conventional, molecular medicine that focuses on targeting specific pathways, stem cell therapy aims to perturb many related mechanisms in order to derive therapeutic benefit. This emerging modality is inherently complex due to the variety of cell types that can be used, delivery approaches that need to be optimized in order to target the cellular therapeutic to specific sites in vivo, and non-invasive imaging methods that are needed to monitor cell fate. This review highlights advancements in the field, with focus on recent publications that use preclinical animal models for cardiovascular stem cell therapy. It highlights studies where cell adhesion engineering (CAE) has been used to functionalize stem cells to home them to sites of therapy, much like peripheral blood neutrophils. It also describes the current state of molecular imaging approaches that aim to non-invasively track the spatio-temporal pattern of stem cell delivery in living subjects.

  5. Human stem cells as a model of motoneuron development and diseases

    Science.gov (United States)

    Liu, Yan; Zhang, Su-Chun

    2010-01-01

    Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) possess potentiality to produce all cell and tissue types of the human body. Under chemically defined culture systems, hESCs and hiPSCs have been efficiently directed to functional spinal motoneurons and astrocytes. The differentiation process faithfully recapitulates the developmental process predicted from studies in vertebrate animals and human specimens, suggesting the usefulness of stem cell differentiation systems in understanding human cellular development. Motoneurons and astrocytes differentiated from genetically altered hESCs or disease hiPSCs exhibit predicted phenotypes. They thus offer a simplified dynamic model for analyzing pathological processes that lead to human motoneuron degeneration, which in turn may serve as a template for pharmaceutical screening. In addition, the human stem cell-derived motoneurons and astrocytes, including those specifically derived from a patient, may become a source for cell therapy. PMID:20536934

  6. Stem cell therapy for joint problems using the horse as a clinically relevant animal model

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Betts, Dean H.

    2007-01-01

    of the developmental biology of synovial joints and their pathologies. Before human clinical trials are undertaken, stem cell-based therapies for non-life-threatening disorders should be evaluated for their safety and efficacy using animal models of spontaneous disease and not solely by the existing laboratory models...... of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

  7. CD105+-mesenchymal stem cells migrate into osteoarthritis joint: An animal model.

    Science.gov (United States)

    Fernandez-Pernas, Pablo; Rodríguez-Lesende, Iván; de la Fuente, Alexandre; Mateos, Jesús; Fuentes, Isaac; De Toro, Javier; Blanco, Fco J; Arufe, M C

    2017-01-01

    Mesenchymal stem cells are being the focus of connective tissue technology and regenerative medicine, presenting a good choice cell source for improving old and well recognized techniques of cartilage defect repair. For instance, the autologous chondrocyte transplantation using new concepts of regenerative medicine. The present study investigated the risk of xenogenicity of human synovial membrane-derived MSCs, injected into the monkeys using intravenous and intra-articular administration. The animal models used were adult monkeys Rhesus which had been injured into the left knee to create an Osteoarthritis (OA) animal model. CD105+-MSCs were injected twice into the OA monkeys with an interval of one week between them. The animals were euthanized one month after treatment. Immunohistochemistry analysis of different organs: spleen, heart, fat, liver, gut, pancreas, lung, skeletal muscle and kidney from the animals revealed that CD105+-MSCs migrated towards the injured knee joint. MSCs naive were found statistically significant increased in the injured knee in front of healthy one. CD105+-MSCs were negatives for CD68 and the area where CD105+-MSCs were found presented SDF-1 increased levels in front of healthy knee. We concluded that a characterized MSCs subset could be a safe alternative for cell therapy in clearly localized pathologies.

  8. Veterinary applications of induced pluripotent stem cells: regenerative medicine and models for disease?

    Science.gov (United States)

    Cebrian-Serrano, Alberto; Stout, Tom; Dinnyes, Andras

    2013-10-01

    Induced pluripotent stem cells (iPSCs) can now be derived from a tissue biopsy and represent a promising new platform for disease modelling, drug and toxicity testing, biomarker development and cell-based therapies for regenerative medicine. In regenerative medicine, large animals may represent the best models for man, and thereby provide invaluable systems in which to test the safety and the potential of iPSCs. Hence, testing iPSCs in veterinary species may serve a double function, namely, developing therapeutic products for regenerative medicine in veterinary patients while providing valuable background information for human clinical trials. The production of iPSCs from livestock or wild species is attractive because it could improve efficiency and reduce costs in various fields, such as transgenic animal generation and drug development, preservation of biological diversity, and because it also offers an alternative to xenotransplantation for in vivo generation of organs. Although the technology of cellular reprogramming using the so-called 'Yamanaka factors' is in its peak expectation phase and many concerns still need to be addressed, the rapid technical progress suggests that iPSCs could contribute significantly to novel therapies in veterinary and biomedical practice in the near future. This review provides an overview of the potential applications of iPSCs in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Cardiac regeneration using pluripotent stem cells—Progression to large animal models

    Directory of Open Access Journals (Sweden)

    James J.H. Chong

    2014-11-01

    Full Text Available Pluripotent stem cells (PSCs have indisputable cardiomyogenic potential and therefore have been intensively investigated as a potential cardiac regenerative therapy. Current directed differentiation protocols are able to produce high yields of cardiomyocytes from PSCs and studies in small animal models of cardiovascular disease have proven sustained engraftment and functional efficacy. Therefore, the time is ripe for cardiac regenerative therapies using PSC derivatives to be tested in large animal models that more closely resemble the hearts of humans. In this review, we discuss the results of our recent study using human embryonic stem cell derived cardiomyocytes (hESC-CM in a non-human primate model of ischemic cardiac injury. Large scale remuscularization, electromechanical coupling and short-term arrhythmias demonstrated by our hESC-CM grafts are discussed in the context of other studies using adult stem cells for cardiac regeneration.

  10. Role model and prototype matching: Upper-secondary school students’ meetings with tertiary STEM students

    Directory of Open Access Journals (Sweden)

    Eva Lykkegaard

    2016-04-01

    Full Text Available Previous research has found that young people’s prototypes of science students and scientists affect their inclination to choose tertiary STEM programs (Science, Technology, Engineering and Mathematics. Consequently, many recruitment initiatives include role models to challenge these prototypes. The present study followed 15 STEM-oriented upper-secondary school students from university-distant backgrounds during and after their participation in an 18-months long university-based recruitment and outreach project involving tertiary STEM students as role models. The analysis focusses on how the students’ meetings with the role models affected their thoughts concerning STEM students and attending university. The regular self-to-prototype matching process was shown in real-life role-models meetings to be extended to a more complex three-way matching process between students’ self-perceptions, prototype images and situation-specific conceptions of role models. Furthermore, the study underlined the positive effect of prolonged role-model contact, the importance of using several role models and that traditional school subjects catered more resistant prototype images than unfamiliar ones did.

  11. Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model.

    Science.gov (United States)

    Chong, Alphonsus K S; Ang, Abel D; Goh, James C H; Hui, James H P; Lim, Aymeric Y T; Lee, Eng Hin; Lim, Beng Hai

    2007-01-01

    A repaired tendon needs to be protected for weeks until it has accrued enough strength to handle physiological loads. Tissue-engineering techniques have shown promise in the treatment of tendon and ligament defects. The present study tested the hypothesis that bone marrow-derived mesenchymal stem cells can accelerate tendon-healing after primary repair of a tendon injury in a rabbit model. Fifty-seven New Zealand White rabbits were used as the experimental animals, and seven others were used as the source of bone marrow-derived mesenchymal stem cells. The injury model was a sharp complete transection through the midsubstance of the Achilles tendon. The transected tendon was immediately repaired with use of a modified Kessler suture and a running epitendinous suture. Both limbs were used, and each side was randomized to receive either bone marrow-derived mesenchymal stem cells in a fibrin carrier or fibrin carrier alone (control). Postoperatively, the rabbits were not immobilized. Specimens were harvested at one, three, six, and twelve weeks for analysis, which included evaluation of gross morphology (sixty-two specimens), cell tracing (twelve specimens), histological assessment (forty specimens), immunohistochemistry studies (thirty specimens), morphometric analysis (forty specimens), and mechanical testing (sixty-two specimens). There were no differences between the two groups with regard to the gross morphology of the tendons. The fibrin had degraded by three weeks. Cell tracing showed that labeled bone marrow-derived mesenchymal stem cells remained viable and present in the intratendinous region for at least six weeks, becoming more diffuse at later time-periods. At three weeks, collagen fibers appeared more organized and there were better morphometric nuclear parameters in the treatment group (p tendon repair can improve histological and biomechanical parameters in the early stages of tendon-healing.

  12. Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure.

    Science.gov (United States)

    Ramanathan, Rajesh; Pettinato, Giuseppe; Beeston, John T; Lee, David D; Wen, Xuejun; Mangino, Martin J; Fisher, Robert A

    2015-08-01

    Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF. Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF. A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen. Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. [STEM on Station Education

    Science.gov (United States)

    Lundebjerg, Kristen

    2016-01-01

    The STEM on Station team is part of Education which is part of the External Relations organization (ERO). ERO has traditional goals based around BHAG (Big Hairy Audacious Goal). The BHAG model is simplified to a saying: Everything we do stimulates actions by others to advance human space exploration. The STEM on Station education initiate is a project focused on bringing off the earth research and learning into classrooms. Educational resources such as lesson plans, activities to connect with the space station and STEM related contests are available and hosted by the STEM on Station team along with their partners such as Texas Instruments. These educational activities engage teachers and students in the current happenings aboard the international space station, inspiring the next generation of space explorers.

  14. Dynamic root uptake model for neutral lipophilic organics

    DEFF Research Database (Denmark)

    Trapp, Stefan

    2002-01-01

    and output to stem with the transpiration stream plus first-order metabolism and dilution by exponential growth. For chemicals with low or intermediate lipophilicity (log Kow , 2), there was no relevant difference between dynamic model and equilibrium approach. For lipophilic compounds, the dynamic model...

  15. ConfChem Conference on Flipped Classroom: Improving Student Engagement in Organic Chemistry Using the Inverted Classroom Model

    Science.gov (United States)

    Rossi, Robert D.

    2015-01-01

    Improving student engagement in STEM (science, technology, engineering, and mathematics) courses generally, and organic chemistry specifically, has long been a goal for educators. Recently educators at all academic levels have been exploring the "inverted classroom" or "flipped classroom" pedagogical model for improving student…

  16. Inactivation of Salmonella in grape tomato stem scars by organic acid wash and chitosan-allyl isothiocyanate coating.

    Science.gov (United States)

    Mukhopadhyay, Sudarsan; Sokorai, Kimberly; Ukuku, Dike O; Jin, Tony; Fan, Xuetong; Olanya, Modesto; Juneja, Vijay

    2018-02-02

    The objective of this study was to evaluate inactivation of inoculated Salmonella enterica on grape tomato stem scars exploiting integrated treatment of organic acid wash (AW) followed by chitosan-allyl isothiocyanate (CT-AIT) coating. The treatment effect on microbial loads and fruit quality during 21days storage at 10°C was also determined. A bacterial cocktail containing three serotypes of Salmonella enterica was used for this study based on their association with produce-related outbreaks. Tomatoes were spot inoculated on stem scars and then immersed in an organic acid solution (700ml) containing 0.5% (v/v) each of acetic (AA) and formic acid (FA) to wash under mild agitation for 1min at ambient temperature (22°C) followed by 1min dipping in a coating solution containing 6mlAIT/g CT. AW in 0.5% organic acid (AA+FA) for 1min reduced Salmonella population by 2.7logCFU/g from an initial load of 7.8logCFU/g, while additional coating treatment of AW tomatoes reduced the pathogens on stem scars to undetectable levels (7logCFU/g reduction for the pathogen. Although the populations of Salmonella in the controls (approx. 7.8logCFU/g stem scar) did not change significantly during 21days of storage at 10°C, the populations were reduced to undetectable level in the integrated (AW plus CT-AIT) treated stem scars on day 1 and no regrowth was observed during storage. The treatment significantly (p<0.05) reduced background bacterial loads to approx. 1.3logCFU/g and the population remained unchanged through day 21 at 10°C. The treatment also completely inactivated mold and yeast on day 1 with no growth reoccurrence. These results indicate that the integrated treatment can provide a safe and effective intervention strategy for grape tomatoes. Published by Elsevier B.V.

  17. Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials.

    Science.gov (United States)

    Giusto, Elena; Donegà, Matteo; Cossetti, Chiara; Pluchino, Stefano

    2014-10-01

    Stem cell technology is a promising branch of regenerative medicine that is aimed at developing new approaches for the treatment of severely debilitating human diseases, including those affecting the central nervous system (CNS). Despite the increasing understanding of the mechanisms governing their biology, the application of stem cell therapeutics remains challenging. The initial idea that stem cell transplants work in vivo via the replacement of endogenous cells lost or damaged owing to disease has been challenged by accumulating evidence of their therapeutic plasticity. This new concept covers the remarkable immune regulatory and tissue trophic effects that transplanted stem cells exert at the level of the neural microenvironment to promote tissue healing via combination of immune modulatory and tissue protective actions, while retaining predominantly undifferentiated features. Among a number of promising candidate stem cell sources, neural stem/precursor cells (NPCs) are under extensive investigation with regard to their therapeutic plasticity after transplantation. The significant impact in vivo of experimental NPC therapies in animal models of inflammatory CNS diseases has raised great expectations that these stem cells, or the manipulation of the mechanisms behind their therapeutic impact, could soon be translated to human studies. This review aims to provide an update on the most recent evidence of therapeutically-relevant neuro-immune interactions following NPC transplants in animal models of multiple sclerosis, cerebral stroke and traumas of the spinal cord, and consideration of the forthcoming challenges related to the early translation of some of these exciting experimental outcomes into clinical medicines. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex......The discovery of tumor stem cells being highly resistant against therapy makes new demands to model systems suitable for evaluation of the effects of new drugs on tumor stem cells. The aim of the present study was therefore to develop an in vivo-like in vitro glioblastoma model for testing...

  19. Protein regulation of induced pluripotent stem cells by transplanting in a Huntington's animal model.

    Science.gov (United States)

    Mu, S; Han, L; Zhou, G; Mo, C; Duan, J; He, Z; Wang, Z; Ren, L; Zhang, J

    2016-10-01

    The purpose of this study was to determine the functional recovery and protein regulation by transplanted induced pluripotent stem cells in a rat model of Huntington's disease (HD). In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle 10 days after the quinolinic acid injection. At 8 weeks after transplantation, fluorodeoxyglucose-PET/CT scan and balance-beam test were performed to evaluate the functional recovery of experimental rats. In addition, immunofluorescence and protein array analysis were used to investigate the regulation of stimulated protein expression in the striatum. At 8 weeks after induced pluripotent stem cell transplantation, motor function was improved in comparison with the quinolinic acid-treated rats. High fluorodeoxyglucose accumulation in the injured striatum was also observed by PET/CT scans. In addition, immunofluorescence analysis demonstrated that implanted cells migrated from the lateral ventricle into the lesioned striatum and differentiated into striatal projection neurons. Array analysis showed a significant upregulation of GFR (Glial cell line-derived neurotrophic factor receptor) alpha-1, Adiponectin/Acrp30, basic-fibroblast growth factors, MIP-1 (Macrophage-inflammatory protein) alpha and leptin, as well as downregulation of cytokine-induced neutrophil chemoattractant-3 in striatum after transplantatation of induced pluripotent stem cells in comparison with the quinolinic acid -treated rats. The findings in this work indicate that transplantation of induced pluripotent stem cells is a promising therapeutic candidate for HD. © 2016 British Neuropathological Society.

  20. Release of acetylcholine from murine embryonic stem cells: effect of nicotinic and muscarinic receptors and blockade of organic cation transporter.

    Science.gov (United States)

    Wessler, Ignaz; Michel-Schmidt, Rosmarie; Dohle, Eva; Kirkpatrick, Charles James

    2012-11-27

    The non-neuronal cholinergic system is widely expressed in nature. The present experiments were performed to characterize the non-neuronal cholinergic system in murine embryonic stem cells (CGR8 cell line). CGR8 cells were cultured in gelatinized flasks with Glasgow's buffered minimal essential medium (Gibco, Germany). Acetylcholine was measured by HPLC combined with bioreactor and electrochemical detection. CGR8 cells contained 1.08±0.12 pmol acetylcholine/10(6) cells (n=7) which was reduced to 0.50±0.06 pmol/10(6) cells (n=6; pacetylcholine into the incubation medium was demonstrated, when cholinesterase activity was blocked by 10 μM physostigmine, with 97±13, 180±15 and 216±14 pmol being released from 65×10(6) cells after incubation periods of 2, 4 and 6h, respectively. The cumulative release corresponds to a fractional release rate of 2%/min. Blockade of nicotine or muscarine receptors did not significantly modulate the release of acetylcholine which was substantially reduced by 300 μM quinine (inhibitor of organic cation transporters). This inhibition showed considerable fading over the incubation period, indicating additional release mechanisms activated upon inhibition of organic cation transporters. Murine embryonic stem cells contain and release significant amounts of acetylcholine. The high fractional release rate and the compensation for blocked organic cation transporters indicate that non-neuronal acetylcholine may play a functional role in the homeostasis of murine embryonic stem cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Virtuous organization: A structural equation modeling approach

    Directory of Open Access Journals (Sweden)

    Majid Zamahani

    2013-02-01

    Full Text Available For years, the idea of virtue was unfavorable among researchers and virtues were traditionally considered as culture-specific, relativistic and they were supposed to be associated with social conservatism, religious or moral dogmatism, and scientific irrelevance. Virtue and virtuousness have been recently considered seriously among organizational researchers. The proposed study of this paper examines the relationships between leadership, organizational culture, human resource, structure and processes, care for community and virtuous organization. Structural equation modeling is employed to investigate the effects of each variable on other components. The data used in this study consists of questionnaire responses from employees in Payam e Noor University in Yazd province. A total of 250 questionnaires were sent out and a total of 211 valid responses were received. Our results have revealed that all the five variables have positive and significant impacts on virtuous organization. Among the five variables, organizational culture has the most direct impact (0.80 and human resource has the most total impact (0.844 on virtuous organization.

  2. Skin-derived mesenchymal stem cells help restore function to ovaries in a premature ovarian failure mouse model.

    Directory of Open Access Journals (Sweden)

    Dongmei Lai

    Full Text Available Skin-derived mesenchymal stem cells (SMSCs can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs and male skin-derived mesenchymal stem cells (M-SMSCs from red fluorescence protein (RFP transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.

  3. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Ivana Antonucci

    2016-04-01

    Full Text Available In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

  4. STEM Engagement with NASA's Solar System Treks Portals for Lunar and Planetary Mapping and Modeling

    Science.gov (United States)

    Law, E. S.; Day, B. H.

    2018-01-01

    This presentation will provide an overview of the uses and capabilities of NASA's Solar System Treks family of online mapping and modeling portals. While also designed to support mission planning and scientific research, this presentation will focus on the Science, Technology, Engineering, and Math (STEM) engagement and public outreach capabilities of these web based suites of data visualization and analysis tools.

  5. Investigating and modeling the pyrolysis kinetic of leaves and stems of pistachio trees for biofuel production

    Directory of Open Access Journals (Sweden)

    M Ostad Hoseini

    2016-09-01

    500°C with 30 minutes residence time. The instantaneous amount (in decimal of the produced gas (M and char (Ms as a function of time (t was modeled using the following equations: For each experiment B is a constant value and is represented by: Where Ea is the activation energy, R is universal gas constant, T is the temperature of the experiment and A is the pre-exponential constant. By having M or Ms at different times (t, the parameters of A, B and Ea were estimated using the curve fitting tool box of the MATLAB® software. Results and Discussion The results of chemical analysis indicated that the leaves powders contained 1.5% N, 42.1% C, 5.5% H, 0.4% S and 48.3% O while the stem samples contained 0.5% N, 46.5% C, 6.1% H, 0.2% S and 44.6% O. Higher amount of carbon and hydrogen in the stem leaves indicates that the stem should have higher energy content. In fact, the calculated high and low heating values for leaves were 17.23 and 16.03 MJ.kg-1, and for the stems were 18.91 and 17.59 MJ.kg-1, respectively which comply with the predicted results from chemical analysis of the powders. The TGA test results indicated that the initial weight loss took place up to 270°C for the stems powder and up to 220°C for leaves powders. This weight loss was due to loss of moisture and volatile compounds. The actual degradation temperature for the stem powders ranged from 300 to 500°C while for the leaves was from 350 to 600°C. The results of pyrolysis experiments indicated that the pyrolysis of stems took place faster than leaves. The pyrolysis time was 10 to 15 min for leaves and 5 to 10 min for stems. The resulting char for pyrolysis of stem was 30% and for stems were 40% of the original materials. The kinetic of pyrolysis was modeled using one-step global model for production of char and gas. The experimental data were fitted to the used model with high degrees of accuracy (R2>0.99. The model parameters, namely activation energy and frequency factors were 10.70 kJ.mol-1, and

  6. Stem cell proliferation and differentiation a multitype branching process model

    CERN Document Server

    Macken, Catherine A

    1988-01-01

    The body contains many cellular systems that require the continuous production of new, fully functional, differentiated cells to replace cells lacking or having limited self-renewal capabilities that die or are damaged during the lifetime of an individual. Such systems include the epidermis, the epithelial lining of the gut, and the blood. For example, erythrocytes (red blood cells) lack nuclei and thus are incapable of self-replication. They have a life span in the circulation of about 120 days. Mature granulocytes, which also lack proliferative capacity, have a much shorter life span - typically 12 hours, though this may be reduced to only two or three hours in times of serious tissue infection. Perhaps a more familiar example is the outermost layer of the skin. This layer is composed of fully mature, dead epidermal cells that must be replaced by the descendants of stem cells lodged in lower layers of the epidermis (cf. Alberts et al. , 1983). In total, to supply the normal steady-state demands of cells, an...

  7. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    OpenAIRE

    Babaei, Parvin; Soltani Tehrani, Bahram; Alizadeh, Arsalan

    2012-01-01

    The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells ( 5 0 0 × 1 0 3 / ...

  8. Modeling global persistent organic chemicals in clouds

    Science.gov (United States)

    Mao, Xiaoxuan; Gao, Hong; Huang, Tao; Zhang, Lisheng; Ma, Jianmin

    2014-10-01

    A cloud model was implemented in a global atmospheric transport model to simulate cloud liquid water content and quantify the influence of clouds on gas/aqueous phase partitioning of persistent organic chemicals (POCs). Partitioning fractions of gas/aqueous and particle phases in clouds for three POCs α-hexachlorocyclohexane (α-HCH), polychlorinated biphenyl-28 (PCB-28), and PCB-138 in a cloudy atmosphere were estimated. Results show that the partition fraction of these selected chemicals depend on cloud liquid water content (LWC) and air temperature. We calculated global distribution of water droplet/ice particle-air partitioning coefficients of the three chemicals in clouds. The partition fractions at selected model grids in the Northern Hemisphere show that α-HCH, a hydrophilic chemical, is sorbed strongly onto cloud water droplets. The computed partition fractions at four selected model grids show that α-HCH tends to be sorbed onto clouds over land (source region) from summer to early fall, and over ocean from late spring to early fall. 20-60% of α-HCH is able to be sorbed to cloud waters over mid-latitude oceans during summer days. PCB-138, one of hydrophobic POCs, on the other hand, tends to be sorbed to particles in the atmosphere subject to air temperature. We also show that, on seasonal or annual average, 10-20% of averaged PCB-28 over the Northern Hemisphere could be sorbed onto clouds, leading to reduction of its gas-phase concentration in the atmosphere.

  9. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  10. Stem cell dynamics in muscle regeneration: Insights from live imaging in different animal models.

    Science.gov (United States)

    Ratnayake, Dhanushika; Currie, Peter D

    2017-06-01

    In recent years, live imaging has been adopted to study stem cells in their native environment at cellular resolution. In the skeletal muscle field, this has led to visualising the initial events of muscle repair in mouse, and the entire regenerative response in zebrafish. Here, we review recent discoveries in this field obtained from live imaging studies. Tracking of tissue resident stem cells, the satellite cells, following injury has captured the morphogenetic dynamics of stem/progenitor cells as they facilitate repair. Asymmetric satellite cell division generated a clonogenic progenitor pool, providing in vivo validation for this mechanism. Furthermore, there is an emerging role of stem/progenitor cell guidance at the injury site by cellular protrusions. This review concludes that live imaging is a critical tool for discovering the distinct processes that occur during regeneration, emphasising the importance of imaging in diverse animal models to capture the entire scope of stem cell functions. Also see the Video Abstract. Link to: https://youtube/tgUHSBD1N0g. © 2017 WILEY Periodicals, Inc.

  11. Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome.

    Science.gov (United States)

    Pawlikowski, Bradley; Betta, Nicole Dalla; Elston, Tiffany; Williams, Darian A; Olwin, Bradley B

    2018-03-09

    Down syndrome, caused by trisomy 21, is characterized by a variety of medical conditions including intellectual impairments, cardiovascular defects, blood cell disorders and pre-mature aging phenotypes. Several somatic stem cell populations are dysfunctional in Down syndrome and their deficiencies may contribute to multiple Down syndrome phenotypes. Down syndrome is associated with muscle weakness but skeletal muscle stem cells or satellite cells in Down syndrome have not been investigated. We find that a failure in satellite cell expansion impairs muscle regeneration in the Ts65Dn mouse model of Down syndrome. Ts65Dn satellite cells accumulate DNA damage and over express Usp16, a histone de-ubiquitinating enzyme that regulates the DNA damage response. Impairment of satellite cell function, which further declines as Ts65Dn mice age, underscores stem cell deficiencies as an important contributor to Down syndrome pathologies.

  12. In vivo tracking of stem cells labeled with a nanoparticle in Alzheimer's disease animal model

    Science.gov (United States)

    Ha, Sungji; Suh, Yoo-Hun; Chang, Keun-A.

    2013-05-01

    Stem cell therapy is a promising tool for the treatment of diverse conditions including neurodegenerative diseases. To understand transplanted stem cell biology, in vivo imaging is necessary. Nano material has great potential for in vivo imaging and several noninvasive methods are used such as magnetic resonance imaging (MRI), positron emission tomography (PET), Fluorescence imaging (FI) and Near-infrared fluorescence imaging (NIRFI). However, each method has limitations for in vivo imaging. To overcome these limitations, multimodal nanoprobes have been developed. In the present study, we intravenously injected human adipose derived stem cells (hASCs) that labeled with multimodal nano particle, LEO-LIVETM-Magnoxide 797 or 675, into the Tg2576 mice, Alzheimer's disease (AD) mouse model. Sequential in vivo tracking was performed with mice injected with hASCs. We could found fluorescence signals until 10 days after injection.

  13. Human pluripotent stem cells as tools for neurodegenerative and neurodevelopmental disease modeling and drug discovery.

    Science.gov (United States)

    Corti, Stefania; Faravelli, Irene; Cardano, Marina; Conti, Luciano

    2015-06-01

    Although intensive efforts have been made, effective treatments for neurodegenerative and neurodevelopmental diseases have not been yet discovered. Possible reasons for this include the lack of appropriate disease models of human neurons and a limited understanding of the etiological and neurobiological mechanisms. Recent advances in pluripotent stem cell (PSC) research have now opened the path to the generation of induced pluripotent stem cells (iPSCs) starting from somatic cells, thus offering an unlimited source of patient-specific disease-relevant neuronal cells. In this review, the authors focus on the use of human PSC-derived cells in modeling neurological disorders and discovering of new drugs and provide their expert perspectives on the field. The advent of human iPSC-based disease models has fuelled renewed enthusiasm and enormous expectations for insights of disease mechanisms and identification of more disease-relevant and novel molecular targets. Human PSCs offer a unique tool that is being profitably exploited for high-throughput screening (HTS) platforms. This process can lead to the identification and optimization of molecules/drugs and thus move forward new pharmacological therapies for a wide range of neurodegenerative and neurodevelopmental conditions. It is predicted that improvements in the production of mature neuronal subtypes, from patient-specific human-induced pluripotent stem cells and their adaptation to culture, to HTS platforms will allow the increased exploitation of human pluripotent stem cells in drug discovery programs.

  14. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    Directory of Open Access Journals (Sweden)

    Daniel R. Bayzigitov

    2016-01-01

    Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

  15. Identification of very small embryonic/epiblast-like stem cells (VSELs) circulating in peripheral blood during organ/tissue injuries.

    Science.gov (United States)

    Ratajczak, Mariusz Z; Liu, Rui; Marlicz, Wojciech; Blogowski, Wojciech; Starzynska, Teresa; Wojakowski, Wojciech; Zuba-Surma, Ewa

    2011-01-01

    We have identified in adult tissues a population of pluripotent very small embryonic/epiblast-like stem cells (VSELs) that we hypothesize are deposited at onset of gastrulation in developing tissues and play an important role as backup population of tissue-specific/committed stem cells. We envision that during steady-state conditions these cells may be involved in tissue rejuvenation and in processes of regeneration/repair after organ injuries. VSELs similarly as epiblast-derived migrating primordial germ cells change the epigenetic signature of some of the imprinted genes and therefore remain quiescent in adult tissues. These epigenetic changes in methylation status of imprinted genes prevent them also from teratoma formation. Mounting evidence indicates that VSELs are mobilized into peripheral blood during tissue/organ injuries and enumeration of these cells may be of prognostic value (e.g., in stroke or heart infarct). In this chapter, we will present FACS-based strategies to detect and enumerate these cells in human peripheral blood and umbilical cord blood. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. iSTEM: Promoting Fifth Graders' Mathematical Modeling

    Science.gov (United States)

    Yanik, H. Bahadir; Karabas, Celil

    2014-01-01

    Modeling requires that people develop representations or procedures to address particular problem situations (Lesh et al. 2000). Mathematical modeling is used to describe essential characteristics of a phenomenon or a situation that one intends to study in the real world through building mathematical objects. This article describes how fifth-grade…

  17. The influence of female social models in corporate STEM initiatives on girls' math and science attitudes

    Science.gov (United States)

    Medeiros, Donald J.

    The United States' Science, Technology, Engineering, and Mathematics (STEM) workforce is growing slower than in the past, in comparison to demand, and in comparison to other countries. Competitive talent conditions require the United States to develop a strong pipeline of STEM talent within its own citizens. Given the number of female college graduates and their underrepresentation in the STEM workforce, women provide the greatest opportunity for fulfilling this need. The term social model represents the individuals and media that shape children's self-perceptions. Social models have been shown to positively influence girl's perceptions of the value of math and science as well as their expectations of success. This study examined differences in attitudes towards math and science among student participants in corporate STEM programs. Differences were measured based on participant gender and ethnicity, their mentor's gender and ethnicity, and program design differences. The research purpose was to inform the design of corporate STEM programs to improve female participants' attitudes towards math and science and eventually increase the number of women in the STEM workforce. Over three hundred students in differing corporate STEM programs completed math and science attitudinal scales at the start and end of their programs. Study results revealed, prior to program start, female participants had a better attitude towards math and science than male participants. Analysis of the Trends in International Mathematics and Science Study data showed similar results. Overall program results demonstrated higher post program math and science attitudes with no differences based on gender, age, or ethnicity of the participant or mentor. Participants with high program or mentor satisfaction were found to have higher attitudes towards math and science. These results may suggest improving female academic choice requires more focus on their expectations of success than perceived task

  18. Modeling and Manipulating Human Diseases with Induced Pluripotent Stem Cells, Pig Models and Precision Gene Editing.

    Directory of Open Access Journals (Sweden)

    Yonglun Luo

    2016-06-01

    Full Text Available We have developed systems, e.g. C-Check, that can be used to rapidly select and quantify CRISPR/Cas9 nuclease activity and enrichment of genetically modified cells with desired mutations (Zhou et al., 2016. To facilitate the simultaneous manipulation of multiple genes in cells, we have developed a system that allows concordant delivery of up to 30 sgRNAs into one cell [Johan Vad-Nielsen et al., under review]. Targeted insertion, fluorescent tagging or correction of endogenous genes is of great interest but greatly hampered by the technical difficulties and relatively low homology directed repair efficiency compared to the higher efficiency of NHEJ. Thus, we have developed systems for rapid generation of gene targeting vectors (Luo et al., 2014, lentivirus-mediated gene targeting [Yujia Cai et al., Elife, in revision], and recombinant Cas9s to enhance HDR in mammalian cells. Furthermore, to recapitulate the pathogenesis of human diseases, we have developed pig models of breast cancer and diabetes using gene editing and SCNT, as well as human induced pluripotent stem cell models of MCADD.

  19. Reconstruction of 3D tree stem models from low-cost terrestrial laser scanner data

    Science.gov (United States)

    Kelbe, Dave; Romanczyk, Paul; van Aardt, Jan; Cawse-Nicholson, Kerry

    2013-05-01

    With the development of increasingly advanced airborne sensing systems, there is a growing need to support sensor system design, modeling, and product-algorithm development with explicit 3D structural ground truth commensurate to the scale of acquisition. Terrestrial laser scanning is one such technique which could provide this structural information. Commercial instrumentation to suit this purpose has existed for some time now, but cost can be a prohibitive barrier for some applications. As such we recently developed a unique laser scanning system from readily-available components, supporting low cost, highly portable, and rapid measurement of below-canopy 3D forest structure. Tools were developed to automatically reconstruct tree stem models as an initial step towards virtual forest scene generation. The objective of this paper is to assess the potential of this hardware/algorithm suite to reconstruct 3D stem information for a single scan of a New England hardwood forest site. Detailed tree stem structure (e.g., taper, sweep, and lean) is recovered for trees of varying diameter, species, and range from the sensor. Absolute stem diameter retrieval accuracy is 12.5%, with a 4.5% overestimation bias likely due to the LiDAR beam divergence.

  20. Mathematical modelling of phenotypic plasticity and conversion to a stem-cell state under hypoxia

    Science.gov (United States)

    Dhawan, Andrew; Madani Tonekaboni, Seyed Ali; Taube, Joseph H.; Hu, Stephen; Sphyris, Nathalie; Mani, Sendurai A.; Kohandel, Mohammad

    2016-02-01

    Hypoxia, or oxygen deficiency, is known to be associated with breast tumour progression, resistance to conventional therapies and poor clinical prognosis. The epithelial-mesenchymal transition (EMT) is a process that confers invasive and migratory capabilities as well as stem cell properties to carcinoma cells thus promoting metastatic progression. In this work, we examined the impact of hypoxia on EMT-associated cancer stem cell (CSC) properties, by culturing transformed human mammary epithelial cells under normoxic and hypoxic conditions, and applying in silico mathematical modelling to simulate the impact of hypoxia on the acquisition of CSC attributes and the transitions between differentiated and stem-like states. Our results indicate that both the heterogeneity and the plasticity of the transformed cell population are enhanced by exposure to hypoxia, resulting in a shift towards a more stem-like population with increased EMT features. Our findings are further reinforced by gene expression analyses demonstrating the upregulation of EMT-related genes, as well as genes associated with therapy resistance, in hypoxic cells compared to normoxic counterparts. In conclusion, we demonstrate that mathematical modelling can be used to simulate the role of hypoxia as a key contributor to the plasticity and heterogeneity of transformed human mammary epithelial cells.

  1. Health consumers and stem cell therapy innovation: markets, models and regulation.

    Science.gov (United States)

    Salter, Brian; Zhou, Yinhua; Datta, Saheli

    2014-05-01

    Global health consumer demand for stem cell therapies is vibrant, but the supply of treatments from the conventional science-based model of innovation is small and unlikely to increase in the near future. At the same time, several models of medical innovation have emerged that can respond to the demand, often employing a transnational value chain to deliver the product. Much of the commentary has approached the issue from a supply side perspective, demonstrating the extent to which national and transnational regulation fails to impose what are regarded as appropriate standards on the 'illicit' supply of stem cell therapies characterized by little data and poor outcomes. By contrast, this article presents a political economic analysis with a strong demand side perspective, arguing that the problem of what is termed 'stem cell tourism' is embedded in the demand-supply relationship of the health consumer market and its engagement with different types of stem cell therapy innovation. To be meaningful, discussions of regulation must recognize that analysis or risk being sidelined by a market, which ignores their often wishful thinking.

  2. Potential Spermatogenesis Recovery with Bone Marrow Mesenchymal Stem Cells in an Azoospermic Rat Model

    Directory of Open Access Journals (Sweden)

    Deying Zhang

    2014-07-01

    Full Text Available Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy.

  3. NASA GISS Climate Change Research Initiative: A Multidisciplinary Vertical Team Model for Improving STEM Education by Using NASA's Unique Capabilities.

    Science.gov (United States)

    Pearce, M. D.

    2017-12-01

    CCRI is a year-long STEM education program designed to bring together teams of NASA scientists, graduate, undergraduate and high school interns and high school STEM educators to become immersed in NASA research focused on atmospheric and climate changes in the 21st century. GISS climate research combines analysis of global datasets with global models of atmospheric, land surface, and oceanic processes to study climate change on Earth and other planetary atmospheres as a useful tool in assessing our general understanding of climate change. CCRI interns conduct research, gain knowledge in assigned research discipline, develop and present scientific presentations summarizing their research experience. Specifically, CCRI interns write a scientific research paper explaining basic ideas, research protocols, abstract, results, conclusion and experimental design. Prepare and present a professional presentation of their research project at NASA GISS, prepare and present a scientific poster of their research project at local and national research symposiums along with other federal agencies. CCRI Educators lead research teams under the direction of a NASA GISS scientist, conduct research, develop research based learning units and assist NASA scientists with the mentoring of interns. Educators create an Applied Research STEM Curriculum Unit Portfolio based on their research experience integrating NASA unique resources, tools and content into a teacher developed unit plan aligned with the State and NGSS standards. STEM Educators also Integrate and implement NASA unique units and content into their STEM courses during academic year, perform community education STEM engagement events, mentor interns in writing a research paper, oral research reporting, power point design and scientific poster design for presentation to local and national audiences. The CCRI program contributes to the Federal STEM Co-STEM initiatives by providing opportunities, NASA education resources and

  4. Dental Pulp Stem Cells Model Early Life and Imprinted DNA Methylation Patterns.

    Science.gov (United States)

    Dunaway, Keith; Goorha, Sarita; Matelski, Lauren; Urraca, Nora; Lein, Pamela J; Korf, Ian; Reiter, Lawrence T; LaSalle, Janine M

    2017-04-01

    Early embryonic stages of pluripotency are modeled for epigenomic studies primarily with human embryonic stem cells (ESC) or induced pluripotent stem cells (iPSCs). For analysis of DNA methylation however, ESCs and iPSCs do not accurately reflect the DNA methylation levels found in preimplantation embryos. Whole genome bisulfite sequencing (WGBS) approaches have revealed the presence of large partially methylated domains (PMDs) covering 30%-40% of the genome in oocytes, preimplantation embryos, and placenta. In contrast, ESCs and iPSCs show abnormally high levels of DNA methylation compared to inner cell mass (ICM) or placenta. Here we show that dental pulp stem cells (DPSCs), derived from baby teeth and cultured in serum-containing media, have PMDs and mimic the ICM and placental methylome more closely than iPSCs and ESCs. By principal component analysis, DPSC methylation patterns were more similar to two other neural stem cell types of human derivation (EPI-NCSC and LUHMES) and placenta than were iPSCs, ESCs or other human cell lines (SH-SY5Y, B lymphoblast, IMR90). To test the suitability of DPSCs in modeling epigenetic differences associated with disease, we compared methylation patterns of DPSCs derived from children with chromosome 15q11.2-q13.3 maternal duplication (Dup15q) to controls. Differential methylation region (DMR) analyses revealed the expected Dup15q hypermethylation at the imprinting control region, as well as hypomethylation over SNORD116, and novel DMRs over 147 genes, including several autism candidate genes. Together these data suggest that DPSCs are a useful model for epigenomic and functional studies of human neurodevelopmental disorders. Stem Cells 2017;35:981-988. © 2016 AlphaMed Press.

  5. Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

    The human blood brain barrier has yet to be successfully replicated as an in vitro model. One of the more promising approaches has been to develop an in vitro model derived from human pluripotent stem cells. However, as promising as this model may be, a successful replication of the differentiation...... method on different kinds of pluripotent stem cell lines have yet to be accomplished. We try to approach the promising method as described by Stebbins et al. (2015) to differentiate human pluripotent stem cells into brain like endothelial cells (BECs). Five different human pluripotent stem cell lines...... were screened for the possibility to differentiate into BECs. Tüb1159, Tüb16423, Bioni010-C, WTSli024-A and WTSli002-A stem cell lines were initially seeded on Matrigel cultured with mTESR1 media to confluence, then seeded on Matrigel as a single cell suspension. After two-three days of culture we...

  6. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

  7. From teeth, skin, blood to heart : induced pluripotent stem cells as an in vitro model for cardiac disease

    NARCIS (Netherlands)

    Dambrot, Cheryl Susan

    2014-01-01

    Since the first reports of human induced pluripotent stem cells (hiPSC), the field of pluripotent stem cell (PSC) research has grown in leap and bounds, particularly in the area of (cardiac) disease modeling. This is in part because it is fairly easy to produce cardiomyocytes from hPSC and also

  8. Mobilized peripheral blood stem cells provide rapid reconstitution but impaired long-term engraftment in a mouse model

    NARCIS (Netherlands)

    Yeoh, J. S. G.; Ausema, A.; Wierenga, P.; de Haan, G.; van Os, R.

    In this study, we use competitive repopulation to compare the quality and frequency of stem cells isolated from mobilized blood with stem cells isolated from bone marrow (BM) in a mouse model. Lin(-)Sca-1(+)c-Kit(+) (LSK) cells were harvested from control BM and peripheral blood of mice following

  9. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model

    DEFF Research Database (Denmark)

    Tønnesen, Jan; Parish, Clare L; Sørensen, Andreas T

    2011-01-01

    Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral...

  10. COMPUTER MODEL FOR ORGANIC FERTILIZER EVALUATION

    Directory of Open Access Journals (Sweden)

    Zdenko Lončarić

    2009-12-01

    Full Text Available Evaluation of manures, composts and growing media quality should include enough properties to enable an optimal use from productivity and environmental points of view. The aim of this paper is to describe basic structure of organic fertilizer (and growing media evaluation model to present the model example by comparison of different manures as well as example of using plant growth experiment for calculating impact of pH and EC of growing media on lettuce plant growth. The basic structure of the model includes selection of quality indicators, interpretations of indicators value, and integration of interpreted values into new indexes. The first step includes data input and selection of available data as a basic or additional indicators depending on possible use as fertilizer or growing media. The second part of the model uses inputs for calculation of derived quality indicators. The third step integrates values into three new indexes: fertilizer, growing media, and environmental index. All three indexes are calculated on the basis of three different groups of indicators: basic value indicators, additional value indicators and limiting factors. The possible range of indexes values is 0-10, where range 0-3 means low, 3-7 medium and 7-10 high quality. Comparing fresh and composted manures, higher fertilizer and environmental indexes were determined for composted manures, and the highest fertilizer index was determined for composted pig manure (9.6 whereas the lowest for fresh cattle manure (3.2. Composted manures had high environmental index (6.0-10 for conventional agriculture, but some had no value (environmental index = 0 for organic agriculture because of too high zinc, copper or cadmium concentrations. Growing media indexes were determined according to their impact on lettuce growth. Growing media with different pH and EC resulted in very significant impacts on height, dry matter mass and leaf area of lettuce seedlings. The highest lettuce

  11. A simulation model for epidemics of stem rust in ryegrass seed crops.

    Science.gov (United States)

    Pfender, W F; Upper, D

    2015-01-01

    A simulation model (STEMRUST_G, named for stem rust of grasses) was created for stem rust (caused by Puccinia graminis subsp. graminicola) in perennial ryegrass grown to maturity as a seed crop. The model has a daily time step and is driven by weather data and an initial input of disease severity from field observation. Key aspects of plant growth are modeled. Disease severity is modeled as rust population growth, where individuals are pathogen colonies (pustules) grouped in cohorts defined by date of initiation and plant part infected. Infections due to either aerial spread or within-plant contact spread are modeled. Pathogen cohorts progress through life stages that are modeled as disease cycle components (colony establishment, latent period, infectious period, and sporulation) affected by daily weather variables, plant growth, and fungicide application. Fungicide effects on disease cycle components are modeled for two commonly used active ingredients, applied preinfection or postinfection. Previously validated submodels for certain disease cycle components formed the framework for integrating additional processes, and the complete model was calibrated with field data from 10 stem rust epidemics. Discrepancies between modeled outcomes and the calibration data (log10[modeled]-log10[observed]) had a mean near zero but considerable variance, with 1 standard deviation=0.5 log10 units (3.2-fold). It appears that a large proportion of the modeling error variance may be due to variability in field observations of disease severity. An action threshold for fungicide application was derived empirically, using a constructed weather input file favorable for disease development. The action threshold is a negative threshold, representing a level of disease (latent plus visible) below which damaging levels of disease are unable to develop before the yield-critical crop stage. The model is in the public domain and available on the Internet.

  12. Organic production in a dynamic CGE model

    DEFF Research Database (Denmark)

    Jacobsen, Lars Bo

    2004-01-01

    Concerns about the impact of modern agriculture on the environment have in recent years led to an interest in supporting the development of organic farming. In addition to environmental benefits, the aim is to encourage the provision of other “multifunctional” properties of organic farming...... agricultural sector and each secondary food industry has been split into two separate industries: one producing organic products, the other producing conventional products. The substitution nests in private consumption have also been altered to emphasise the pair wise substitution between organic...... and conventional products. One of the most important regulations regarding organic production concerns the conversion period, that is the period where the farmer starts to use organic production methods until the farmland and the production are considered organic. Currently organic production methods have...

  13. Modeling of desorption of Alfalfa (Medicago sativa) stems and leaves.

    NARCIS (Netherlands)

    ArabHosseini, A.; Huisman, W.; Müller, J.

    2011-01-01

    The equilibrium moisture content of agricultural products is necessary to optimize drying process and helps to keep the quality of the product during the period of storage. The main aim of this research was to find the best model which could define well, the exchange of moisture between alfalfa

  14. Societal value of stem cell therapy in stroke--a modeling study.

    Science.gov (United States)

    Svensson, Johanna; Ghatnekar, Ola; Lindgren, Arne; Lindvall, Olle; Norrving, Bo; Persson, Ulf; Kokaia, Zaal

    2012-01-01

    Stroke is one of the major causes of disability in the adult population and represents a heavy social and economic burden. Currently available therapeutic tools to support the recovery of impaired brain functions are quite limited. Animal studies have demonstrated that neuronal replacement and partial reconstruction of neural circuitry or modulation of the recovery process is possible with cell transplantation in the damaged adult brain. Stem cell therapy (SCT) may promote functional recovery also in stroke patients, thereby improving quality of life and reducing costs. Our aim was to estimate the potential societal value of SCT in stroke patients. We created a decision-analytic model in Microsoft Excel 2010 to assess life-long costs and quality-adjusted life years (QALYs) of SCT versus standard care for stroke patients from a societal perspective. The model structure consisted of 7 health states in accordance with the modified Rankin Scale (mRS). We modeled for age (55, 65, and 75 years), functional status at discharge (mRS 2, 3, and 4), effectiveness of SCT (50 and 25% increase in the probability to improve 1 mRS grade), mode of stem cell administration, risk of recurrent stroke, complications of intervention, and use of immunosuppressive drugs. The difference between an assumed societal willingness to pay for a QALY gain in Sweden (110,400 USD) and the cost per QALY gain resulting from the model was interpreted as the value of SCT. Increased survival (1.06 life years) and improved functional status gave rise to an estimated gain of 1.34 QALY in a cohort of patients aged 55 with mRS 2 at hospital discharge. Although the SCT intervention increased costs by 64,014 USD (excluding cost of stem cells), the costs of intervention were offset mainly by decreased productivity losses. In total, the intervention saved 19,055 USD, i.e., at a price of 19,055 USD for stem cells, the SCT would be cost neutral. The societal value of SCT was 166,500 USD. The application of the

  15. Assessment of the primary rotational stability of uncemented hip stems using an analytical model: comparison with finite element analyses.

    Science.gov (United States)

    Zeman, Maria E; Sauwen, Nicolas; Labey, Luc; Mulier, Michiel; Van der Perre, Georges; Jaecques, Siegfried V N

    2008-09-25

    Sufficient primary stability is a prerequisite for the clinical success of cementless implants. Therefore, it is important to have an estimation of the primary stability that can be achieved with new stem designs in a pre-clinical trial. Fast assessment of the primary stability is also useful in the preoperative planning of total hip replacements, and to an even larger extent in intraoperatively custom-made prosthesis systems, which result in a wide variety of stem geometries. An analytical model is proposed to numerically predict the relative primary stability of cementless hip stems. This analytical approach is based upon the principle of virtual work and a straightforward mechanical model. For five custom-made implant designs, the resistance against axial rotation was assessed through the analytical model as well as through finite element modelling (FEM). The analytical approach can be considered as a first attempt to theoretically evaluate the primary stability of hip stems without using FEM, which makes it fast and inexpensive compared to other methods. A reasonable agreement was found in the stability ranking of the stems obtained with both methods. However, due to the simplifying assumptions underlying the analytical model it predicts very rigid stability behaviour: estimated stem rotation was two to three orders of magnitude smaller, compared with the FEM results. Based on the results of this study, the analytical model might be useful as a comparative tool for the assessment of the primary stability of cementless hip stems.

  16. Assessment of the primary rotational stability of uncemented hip stems using an analytical model: Comparison with finite element analyses

    Directory of Open Access Journals (Sweden)

    Van der Perre Georges

    2008-09-01

    Full Text Available Abstract Background Sufficient primary stability is a prerequisite for the clinical success of cementless implants. Therefore, it is important to have an estimation of the primary stability that can be achieved with new stem designs in a pre-clinical trial. Fast assessment of the primary stability is also useful in the preoperative planning of total hip replacements, and to an even larger extent in intraoperatively custom-made prosthesis systems, which result in a wide variety of stem geometries. Methods An analytical model is proposed to numerically predict the relative primary stability of cementless hip stems. This analytical approach is based upon the principle of virtual work and a straightforward mechanical model. For five custom-made implant designs, the resistance against axial rotation was assessed through the analytical model as well as through finite element modelling (FEM. Results The analytical approach can be considered as a first attempt to theoretically evaluate the primary stability of hip stems without using FEM, which makes it fast and inexpensive compared to other methods. A reasonable agreement was found in the stability ranking of the stems obtained with both methods. However, due to the simplifying assumptions underlying the analytical model it predicts very rigid stability behaviour: estimated stem rotation was two to three orders of magnitude smaller, compared with the FEM results. Conclusion Based on the results of this study, the analytical model might be useful as a comparative tool for the assessment of the primary stability of cementless hip stems.

  17. International Society for Stem Cell Research

    Science.gov (United States)

    ... renowned stem cell and regenerative medicine community. More stem cell research Take a closer look Recent Blogs View All ... story independent nonprofit organization & the voice of the stem cell research community The International Society for Stem Cell Research ( ...

  18. Three-dimensional cell culture model utilization in cancer stem cell research.

    Science.gov (United States)

    Bielecka, Zofia F; Maliszewska-Olejniczak, Kamila; Safir, Ilan J; Szczylik, Cezary; Czarnecka, Anna M

    2017-08-01

    Three-dimensional (3D) cell culture models are becoming increasingly popular in contemporary cancer research and drug resistance studies. Recently, scientists have begun incorporating cancer stem cells (CSCs) into 3D models and modifying culture components in order to mimic in vivo conditions better. Currently, the global cell culture market is primarily focused on either 3D cancer cell cultures or stem cell cultures, with less focus on CSCs. This is evident in the low product availability officially indicated for 3D CSC model research. This review discusses the currently available commercial products for CSC 3D culture model research. Additionally, we discuss different culture media and components that result in higher levels of stem cell subpopulations while better recreating the tumor microenvironment. In summary, although progress has been made applying 3D technology to CSC research, this technology could be further utilized and a greater number of 3D kits dedicated specifically to CSCs should be implemented. © 2016 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

  19. The Biological Diversity and Production of Volatile Organic Compounds by Stem-Inhabiting Endophytic Fungi of Ecuador

    Directory of Open Access Journals (Sweden)

    Susan M. Rundell

    2015-12-01

    Full Text Available Fungal endophytes colonize every major lineage of land plants without causing apparent harm to their hosts. Despite their production of interesting and potentially novel compounds, endophytes—particularly those inhabiting stem tissues—are still a vastly underexplored component of microbial diversity. In this study, we explored the diversity of over 1500 fungal endophyte isolates collected from three Ecuadorian ecosystems: lowland tropical forest, cloud forest, and coastal dry forest. We sought to determine whether Ecuador’s fungal endophytes are hyperdiverse, and whether that biological diversity is reflected in the endophytes’ chemical diversity. To assess this chemical diversity, we analyzed a subset of isolates for their production of volatile organic compounds (VOCs, a representative class of natural products. This study yielded a total of 1526 fungal ITS sequences comprising some 315 operational taxonomic units (OTUs, resulting in a non-asymptotic OTU accumulation curve and characterized by a Fisher’s α of 120 and a Shannon Diversity score of 7.56. These figures suggest that the Ecuadorian endophytes are hyperdiverse. Furthermore, the 113 isolates screened for VOCs produced more than 140 unique compounds. These results present a mere snapshot of the remarkable biological and chemical diversity of stem-inhabiting endophytic fungi from a single neotropical country.

  20. The Time Is Right to Focus on Model Organism Metabolomes.

    Science.gov (United States)

    Edison, Arthur S; Hall, Robert D; Junot, Christophe; Karp, Peter D; Kurland, Irwin J; Mistrik, Robert; Reed, Laura K; Saito, Kazuki; Salek, Reza M; Steinbeck, Christoph; Sumner, Lloyd W; Viant, Mark R

    2016-02-15

    Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  1. The Time Is Right to Focus on Model Organism Metabolomes

    Directory of Open Access Journals (Sweden)

    Arthur S. Edison

    2016-02-01

    Full Text Available Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  2. Stem Cell Basics

    Science.gov (United States)

    ... healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of ... as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates ...

  3. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  4. Small animal models to understand pathogenesis of osteoarthritis and use of stem cell in cartilage regeneration.

    Science.gov (United States)

    Piombo, Virginia

    2017-01-01

    Osteoarthritis (OA) is one of the most common diseases, which affect the correct functionality of synovial joints and is characterized by articular cartilage degradation. Limitation in the treatment of OA is mostly due to the very limited regenerative characteristic of articular cartilage once is damaged. Small animal models are of particular importance for mechanistic analysis to understand the processes that affect cartilage degradation. Combination of joint injury techniques with the use of stem cells has been shown to be an important tool for understanding the processes of cartilage degradation and regeneration. Implementation of stem cells and small animal models are important tools to help researchers to find a solution that could ameliorate and prevent the symptoms of OA. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Field assessment of a model for fungicide effects on intraplant spread of stem rust in perennial ryegrass seed crops.

    Science.gov (United States)

    Pfender, W F; Eynard, J

    2009-06-01

    Intraplant spread of stem rust (Puccinia graminis subsp. graminicola) in perennial ryegrass during tiller extension is a major determinant of epidemic severity and is dominated by stem extension dynamics. Simple equations for extension of inflorescence and internodes are presented and parameterized. These equations are combined with previously published equations for pathogen latent period and for postinfection efficacy of fungicides to produce a model for effects of fungicide type and timing on intraplant spread. The model is driven by thermal units, calculated from air temperature measurements. Three field experiments, conducted independently from the field experiments that provided data for plant growth model parameterization, were conducted to assess performance of the disease spread model. Either propiconazole or azoxystrobin, the two most commonly used fungicides for stem rust control, was applied to tillers that had stem rust pustules on the flag sheath and in which the inflorescence was partially extended. Intraplant spread of disease to the extending inflorescence (stem and flowerhead) was observed at several dates following treatment and compared with modeled severities. The model estimated accurately the severities of inflorescence infection for most treatments and observation times, with a correlation coefficient of 0.93 for modeled versus observed disease severities across the three experiments. The model correctly estimated the rank order of final severities among the treatments (fungicide type and timing). The model can be extended to intraplant spread of stem rust at all internodes and incorporated into decision support tools for fungicide type and timing in management of this disease.

  6. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  7. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    Energy Technology Data Exchange (ETDEWEB)

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  8. Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer’s Disease Rat Models

    Directory of Open Access Journals (Sweden)

    Hu Haiyan

    2016-01-01

    Full Text Available Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer’s disease (AD. However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI on the proliferation and differentiation of the engrafted neural stem cells (NSCs, we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models. In vitro experimentation showed that 10−5 M ASI induced NSCs to differentiate into β-tubulin III+ and GFAP+ cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number of β-tubulin III+ cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expression in vitro and in vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway.

  9. A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment

    Science.gov (United States)

    Nör, Jacques Eduardo

    2018-01-01

    Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics. By including the molecular details of IL-6 binding, we are able to quantify the temporal changes in fractional occupancies of bound receptors and their influence on tumor volume. There is a strong correlation between the model output and experimental data for primary tumor xenografts. We also used the model to predict tumor response to administration of the humanized IL-6R monoclonal antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ administered weekly for 7 weeks is sufficient to result in tumor reduction and a sustained deceleration of tumor growth. PMID:29351275

  10. Organization model and formalized description of nuclear enterprise information system

    International Nuclear Information System (INIS)

    Yuan Feng; Song Yafeng; Li Xudong

    2012-01-01

    Organization model is one of the most important models of Nuclear Enterprise Information System (NEIS). Scientific and reasonable organization model is the prerequisite that NEIS has robustness and extendibility, and is also the foundation of the integration of heterogeneous system. Firstly, the paper describes the conceptual model of the NEIS on ontology chart, which provides a consistent semantic framework of organization. Then it discusses the relations between the concepts in detail. Finally, it gives the formalized description of the organization model of NEIS based on six-tuple array. (authors)

  11. Impact of tissue surface properties on the desorption electrospray ionization imaging of organic acids in grapevine stem.

    Science.gov (United States)

    Dong, Yonghui; Guella, Graziano; Franceschi, Pietro

    2016-03-30

    Desorption electrospray ionization (DESI) imaging is a fast analytical technique used to assess spatially resolved biological processes over unmodified sample surfaces. Although DESI profiling experiments have demonstrated that the properties of the sample surface significantly affect the outcomes of DESI analyses, the potential implications of these phenomena in imaging applications have not yet been explored extensively. The distribution of endogenous and exogenous organic acids in pith and out pith region of grapevine stems was investigated by using DESI imaging, ion chromatography and direct infusion methods. Several common normalization strategies to account for the surface effect, including TIC normalization, addition of the internal standard in the spray solvent and deposition of the standard over the sample surface, were critically evaluated. DESI imaging results show that, in our case, the measured distributions of these small organic acids are not consistent with their 'true' localizations within the tissues. Furthermore, our results indicate that the common normalization strategies are not able to completely compensate for the observed surface effect. Variations in the tissue surface properties across the tissue sample can greatly affect the semi-quantitative detection of organic acids. Attention should be paid when interpreting DESI imaging results and an independent analytical validation step is important in untargeted DESI imaging investigations. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance.

    Science.gov (United States)

    Leventhal, J; Miller, J; Abecassis, M; Tollerud, D J; Ildstad, S T

    2013-01-01

    The immunoregulatory properties of hematopoietic stem cells (HSCs) have been recognized for more than 60 years, beginning in 1945, when Owen reported that genetically disparate freemartin cattle sharing a common placenta were red blood cell chimeras. In 1953, Billingham, Brent, and Medawar demonstrated that murine neonatal chimeras prepared by infusion of donor-derived hematopoietic cells exhibited donor-specific tolerance to skin allografts. Various approaches using HSCs in organ transplantation have gradually brought closer to reality the dream of inducing donor-specific tolerance in organ transplant recipients. Several hurdles needed to be overcome, especially the risk of graft-versus-host disease (GVHD), the toxicity of ablative conditioning, and the need for close donor-recipient matching. For wide acceptance, HSC therapy must be safe and reproducible in mismatched donor-recipient combinations. Discoveries in other disciplines have often unexpectedly and synergistically contributed to progress in this area. This review presents a historic perspective of the quest for tolerance in organ transplantation, highlighting current clinical approaches.

  13. New neurons for injured brains? The emergence of new genetic model organisms to study brain regeneration.

    Science.gov (United States)

    Fernández-Hernández, Ismael; Rhiner, Christa

    2015-09-01

    Neuronal circuits in the adult brain have long been viewed as static and stable. However, research in the past 20 years has shown that specialized regions of the adult brain, which harbor adult neural stem cells, continue to produce new neurons in a wide range of species. Brain plasticity is also observed after injury. Depending on the extent and permissive environment of neurogenic regions, different organisms show great variability in their capacity to replace lost neurons by endogenous neurogenesis. In Zebrafish and Drosophila, the formation of new neurons from progenitor cells in the adult brain was only discovered recently. Here, we compare properties of adult neural stem cells, their niches and regenerative responses from mammals to flies. Current models of brain injury have revealed that specific injury-induced genetic programs and comparison of neuronal fitness are implicated in brain repair. We highlight the potential of these recently implemented models of brain regeneration to identify novel regulators of stem cell activation and regenerative neurogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pluripotent stem cell-derived kidney organoids : An in vivo-like in vitro technology

    NARCIS (Netherlands)

    Schutgens, Frans|info:eu-repo/dai/nl/41397149X; Verhaar, Marianne C.|info:eu-repo/dai/nl/182921840; Rookmaaker, Maarten B.|info:eu-repo/dai/nl/298655381

    2016-01-01

    Organoids are self-organizing, multicellular structures that contain multiple cell types, represent organ structure and function, and can be used to model organ development, maintenance and repair ex vivo. Organoids, derived from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) or

  15. Induced pluripotent stem cells as a cellular model for studying Down Syndrome

    Directory of Open Access Journals (Sweden)

    Brigida AL

    2016-11-01

    Full Text Available Down Syndrome (DS, or Trisomy 21 Syndrome, is one of the most common genetic diseases. It is a chromosomal abnormality caused by a duplication of chromosome 21. DS patients show the presence of a third copy (or a partial third copy of chromosome 21 (trisomy, as result of meiotic errors. These patients suffer of many health problems, such as intellectual disability, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, immune system deficiencies, muscle hypotonia and motor disorders. About one in 1000 babies born each year are affected by DS. Alterations in the dosage of genes located on chromosome 21 (also called HSA21 are responsible for the DS phenotype. However, the molecular pathogenic mechanisms of DS triggering are still not understood; newest evidences suggest the involvement of epigenetic mechanisms. For obvious ethical reasons, studies performed on DS patients, as well as on human trisomic tissues are limited. Some authors have proposed mouse models of this syndrome. However, not all the features of the syndrome are represented. Stem cells are considered the future of molecular and regenerative medicine. Several types of stem cells could provide a valid approach to offer a potential treatment for some untreatable human diseases. Stem cells also represent a valid system to develop new cell-based drugs and/or a model to study molecular disease pathways. Among stem cell types, patient-derived induced pluripotent stem (iPS cells offer some advantages for cell and tissue replacement, engineering and studying: self-renewal capacity, pluripotency and ease of accessibility to donor tissues. These cells can be reprogrammed into completely different cellular types. They are derived from adult somatic cells via reprogramming with ectopic expression of four transcription factors (Oct3/4, Sox2, c-Myc and Klf4; or, Oct3/4, Sox2, Nanog, and Lin28. By reprogramming cells from DS patients, it is possible to obtain new tissue with

  16. Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    2016-09-01

    Full Text Available Cancer genomics has provided an unprecedented opportunity for understanding genetic causes of human cancer. However, distinguishing which mutations are functionally relevant to cancer pathogenesis remains a major challenge. We describe here a mammary stem cell (MaSC organoid-based approach for rapid generation of somatic genetically engineered mouse models (GEMMs. By using RNAi and CRISPR-mediated genome engineering in MaSC-GEMMs, we have discovered that inactivation of Ptpn22 or Mll3, two genes mutated in human breast cancer, greatly accelerated PI3K-driven mammary tumorigenesis. Using these tumor models, we have also identified genetic alterations promoting tumor metastasis and causing resistance to PI3K-targeted therapy. Both Ptpn22 and Mll3 inactivation resulted in disruption of mammary gland differentiation and an increase in stem cell activity. Mechanistically, Mll3 deletion enhanced stem cell activity through activation of the HIF pathway. Thus, our study has established a robust in vivo platform for functional cancer genomics and has discovered functional breast cancer mutations.

  17. Non-destructive estimation of root pressure using sap flow, stem diameter measurements and mechanistic modelling.

    Science.gov (United States)

    De Swaef, Tom; Hanssens, Jochen; Cornelis, Annelies; Steppe, Kathy

    2013-02-01

    Upward water movement in plants via the xylem is generally attributed to the cohesion-tension theory, as a response to transpiration. Under certain environmental conditions, root pressure can also contribute to upward xylem water flow. Although the occurrence of root pressure is widely recognized, ambiguity exists about the exact mechanism behind root pressure, the main influencing factors and the consequences of root pressure. In horticultural crops, such as tomato (Solanum lycopersicum), root pressure is thought to cause cells to burst, and to have an important impact on the marketable yield. Despite the challenges of root pressure research, progress in this area is limited, probably because of difficulties with direct measurement of root pressure, prompting the need for indirect and non-destructive measurement techniques. A new approach to allow non-destructive and non-invasive estimation of root pressure is presented, using continuous measurements of sap flow and stem diameter variation in tomato combined with a mechanistic flow and storage model, based on cohesion-tension principles. Transpiration-driven sap flow rates are typically inversely related to stem diameter changes; however, this inverse relationship was no longer valid under conditions of low transpiration. This decoupling between sap flow rates and stem diameter variations was mathematically related to root pressure. Root pressure can be estimated in a non-destructive, repeatable manner, using only external plant sensors and a mechanistic model.

  18. Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Pournasr, Behshad; Duncan, Stephen A

    2017-11-01

    Inborn errors of hepatic metabolism are because of deficiencies commonly within a single enzyme as a consequence of heritable mutations in the genome. Individually such diseases are rare, but collectively they are common. Advances in genome-wide association studies and DNA sequencing have helped researchers identify the underlying genetic basis of such diseases. Unfortunately, cellular and animal models that accurately recapitulate these inborn errors of hepatic metabolism in the laboratory have been lacking. Recently, investigators have exploited molecular techniques to generate induced pluripotent stem cells from patients' somatic cells. Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. In this mini-review, we present a brief overview of the state-of-the-art in using pluripotent stem cells for such studies. © 2017 American Heart Association, Inc.

  19. Impaired neural differentiation of induced pluripotent stem cells generated from a mouse model of Sandhoff disease.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ogawa

    Full Text Available Sandhoff disease (SD is a glycosphingolipid storage disease that arises from mutations in the Hexb gene and the resultant deficiency in β-hexosaminidase activity. This deficiency results in aberrant lysosomal accumulation of the ganglioside GM2 and related glycolipids, and progressive deterioration of the central nervous system. Dysfunctional glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. Induced pluripotent stem cell (iPSC technology offers new opportunities for both elucidation of the pathogenesis of diseases and the development of stem cell-based therapies. Here, we report the generation of disease-specific iPSCs from a mouse model of SD. These mouse model-derived iPSCs (SD-iPSCs exhibited pluripotent stem cell properties and significant accumulation of GM2 ganglioside. In lineage-directed differentiation studies using the stromal cell-derived inducing activity method, SD-iPSCs showed an impaired ability to differentiate into early stage neural precursors. Moreover, fewer neurons differentiated from neural precursors in SD-iPSCs than in the case of the wild type. Recovery of the Hexb gene in SD-iPSCs improved this impairment of neuronal differentiation. These results provide new insights as to understanding the complex pathogenic mechanisms of SD.

  20. Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease.

    Science.gov (United States)

    Atmanli, Ayhan; Domian, Ibrahim John

    2017-05-01

    The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in vitro study. Engineering cardiac constructs that recapitulate human development and disease requires faithful recreation of the cardiac niche in vitro. Here we discuss recent progress in translating the in vivo cardiac microenvironment into PSC models of the human heart. We review three key physiologic features required to recreate the cardiac niche and facilitate normal cardiac differentiation and maturation: the biochemical, biophysical, and bioelectrical signaling cues. Finally, we discuss key barriers that must be overcome to fulfill the promise of stem cell biology in preclinical applications and ultimately in clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Flax stems: from a specific architecture to an instructive model for bioinspired composite structures.

    Science.gov (United States)

    Baley, Christophe; Goudenhooft, Camille; Gibaud, Marianne; Bourmaud, Alain

    2018-01-10

    The present paper proposes to carefully study and describe the reinforcement mechanisms within a flax stem, which is an exceptional natural model of composite structure. Thanks to accurate microscopic investigations, with both optical and SEM method, we finely depicted the flax stem architecture, which can be view as a composite structure with an outer protection, a unidirectional ply on the periphery and a porous core; each component has a specific function, such as mechanical reinforcement for the unidirectional ply and the porous core. The significant mechanical role of fibres was underlined, as well as their local organisation in cohesive bundles, obtained because of an intrusive growth and evidenced in this work through nanomechanical AFM measurement and 3D reconstruction. Following a biomimetic approach, these data provide a source of inspiration for the composite materials of tomorrow. © 2018 IOP Publishing Ltd.

  2. Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy.

    Science.gov (United States)

    Vicente-Dueñas, Carolina; Hauer, Julia; Ruiz-Roca, Lucía; Ingenhag, Deborah; Rodríguez-Meira, Alba; Auer, Franziska; Borkhardt, Arndt; Sánchez-García, Isidro

    2015-06-01

    Cancer is a clonal malignant disease originated in a single cell and characterized by the accumulation of partially differentiated cells that are phenotypically reminiscent of normal stages of differentiation. According to current models, therapeutic strategies that block oncogene activity are likely to selectively target tumor cells. However, recent evidences have revealed that cancer stem cells could arise through a tumor stem cell reprogramming mechanism, suggesting that genetic lesions that initiate the cancer process might be dispensable for tumor progression and maintenance. This review addresses the impact of these results toward a better understanding of cancer development and proposes new approaches to treat cancer in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A Bridge to the Stars: A Model High School-to-College Pipeline to Improve Diversity in STEM

    Science.gov (United States)

    McIntosh, Daniel H.; Jennings, Derrick H.

    2017-01-01

    Increasing participation by historically underrepresented Americans in the STEM workforce remains a national priority. Existing strategies have failed to increase diversity especially in the physical sciences despite federal mandates. To meet this urgent challenge, it is imperative to immediately identify and support the expansion of effective high school-to-college STEM pipelines. A Bridge to the Stars (ABttS) is a creative and tested pipeline designed to steadily increase the numbers of disadvantaged 15-21 year-olds pursuing and completing 4-year STEM degrees. This unique program offers extended engagement in astronomy, arguably the most accessible window to science, through a 3-tier STEM immersion program of innovative learning (in a freshman science course), authentic research training (in a freshman science lab), and supportive near-peer mentoring at U.Missouri-Kansas City, an urban research university. Each tier of the ABttS pipeline by itself has the potential to broaden student aspirations for careers as technological innovators or STEM educators. Students who elect to transition through multiple tiers will substantially reinforce their successes with STEM activities, and significantly bolster their self-esteem necessary to personally manifest STEM aspirations. We will summarize the impact of this program after 5 years, and share our latest improvements. The long-term mission of ABttS is to see urban educational institutions across the U.S. adopt similar pipelines in all STEM disciplines built on the ABttS model.

  4. Current state and perspectives in modeling and control of human pluripotent stem cell expansion processes in stirred-tank bioreactors.

    Science.gov (United States)

    Galvanauskas, Vytautas; Grincas, Vykantas; Simutis, Rimvydas; Kagawa, Yuki; Kino-Oka, Masahiro

    2017-03-01

    Implementation of model-based practices for process development, control, automation, standardization, and validation are important factors for therapeutic and industrial applications of human pluripotent stem cells. As robust cultivation strategies for pluripotent stem cell expansion and differentiation have yet to be determined, process development could be enhanced by application of mathematical models and advanced control systems to optimize growth conditions. Therefore, it is important to understand both the potential of possible applications and the apparent limitations of existing mathematical models to improve pluripotent stem cell cultivation technologies. In the present review, the authors focus on these issues as they apply to stem cell expansion processes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:355-364, 2017. © 2017 American Institute of Chemical Engineers.

  5. Replicative senescence of mesenchymal stem cells: a continuous and organized process.

    Directory of Open Access Journals (Sweden)

    Wolfgang Wagner

    Full Text Available Mesenchymal stem cells (MSC comprise a promising tool for cellular therapy. These cells are usually culture expanded prior to their application. However, a precise molecular definition of MSC and the sequel of long-term in vitro culture are yet unknown. In this study, we have addressed the impact of replicative senescence on human MSC preparations. Within 43 to 77 days of cultivation (7 to 12 passages, MSC demonstrated morphological abnormalities, enlargement, attenuated expression of specific surface markers, and ultimately proliferation arrest. Adipogenic differentiation potential decreased whereas the propensity for osteogenic differentiation increased. mRNA expression profiling revealed a consistent pattern of alterations in the global gene expression signature of MSC at different passages. These changes are not restricted to later passages, but are continuously acquired with increasing passages. Genes involved in cell cycle, DNA replication and DNA repair are significantly down-regulated in late passages. Genes from chromosome 4q21 were over-represented among differentially regulated transcripts. Differential expression of 10 genes has been verified in independent donor samples as well as in MSC that were isolated under different culture conditions. Furthermore, miRNA expression profiling revealed an up-regulation of hsa-mir-371, hsa-mir-369-5P, hsa-mir-29c, hsa-mir-499 and hsa-let-7f upon in vitro propagation. Our studies indicate that replicative senescence of MSC preparations is a continuous process starting from the first passage onwards. This process includes far reaching alterations in phenotype, differentiation potential, global gene expression patterns, and miRNA profiles that need to be considered for therapeutic application of MSC preparations.

  6. MODELING OF MANAGEMENT PROCESSES IN AN ORGANIZATION

    Directory of Open Access Journals (Sweden)

    Stefan Iovan

    2016-05-01

    Full Text Available When driving any major change within an organization, strategy and execution are intrinsic to a project’s success. Nevertheless, closing the gap between strategy and execution remains a challenge for many organizations [1]. Companies tend to focus more on execution than strategy for quick results, instead of taking the time needed to understand the parts that make up the whole, so the right execution plan can be put in place to deliver the best outcomes. A large part of this understands that business operations don’t fit neatly within the traditional organizational hierarchy. Business processes are often messy, collaborative efforts that cross teams, departments and systems, making them difficult to manage within a hierarchical structure [2]. Business process management (BPM fills this gap by redefining an organization according to its end-to-end processes, so opportunities for improvement can be identified and processes streamlined for growth, revenue and transformation. This white paper provides guidelines on what to consider when using business process applications to solve your BPM initiatives, and the unique capabilities software systems provides that can help ensure both your project’s success and the success of your organization as a whole. majority of medium and small businesses, big companies and even some guvermental organizations [2].

  7. Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model

    Directory of Open Access Journals (Sweden)

    Kim Bum

    2012-08-01

    Full Text Available Abstract Background Stem cell injection therapies have been proposed to overcome the limited efficacy and adverse reactions of bulking agents. However, most have significant limitations, including painful procurement, requirement for anesthesia, donor site infection and a frequently low cell yield. Recently, human amniotic fluid stem cells (hAFSCs have been proposed as an ideal cell therapy source. In this study, we investigated whether periurethral injection of hAFSCs can restore urethral sphincter competency in a mouse model. Methods Amniotic fluids were collected and harvested cells were analyzed for stem cell characteristics and in vitro myogenic differentiation potency. Mice underwent bilateral pudendal nerve transection to generate a stress urinary incontinence (SUI model and received either periurethral injection of hAFSCs, periurethral injection of Plasma-Lyte (control group, or underwent a sham (normal control group. For in vivo cell tracking, cells were labeled with silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate (MNPs@SiO2 (RITC and were injected into the urethral sphincter region (n = 9. Signals were detected by optical imaging. Leak point pressure and closing pressure were recorded serially after injection. Tumorigenicity of hAFSCs was evaluated by implanting hAFSCs into the subcapsular space of the kidney, followed two weeks later by retrieval and histologic analysis. Results Flow activated cell sorting showed that hAFSCs expressed mesenchymal stem cell (MSC markers, but no hematopoietic stem cell markers. Induction of myogenic differentiation in the hAFSCs resulted in expression of PAX7 and MYOD at Day 3, and DYSTROPHIN at Day 7. The nanoparticle-labeled hAFSCs could be tracked in vivo with optical imaging for up to 10 days after injection. Four weeks after injection, the mean LPP and CP were significantly increased in the hAFSC-injected group compared with the control group. Nerve regeneration and

  8. Self-Organizing Map Models of Language Acquisition

    Directory of Open Access Journals (Sweden)

    Ping eLi

    2013-11-01

    Full Text Available Connectionist models have had a profound impact on theories of language. While most early models were inspired by the classic PDP architecture, recent models of language have explored various other types of models, including self-organizing models for language acquisition. In this paper we aim at providing a review of the latter type of models, and highlight a number of simulation experiments that we have conducted based on these models. We show that self-organizing connectionist models can provide significant insights into long-standing debates in both monolingual and bilingual language development.

  9. Evidence for Karyotype Polymorphism in the Free-Living Flatworm, Macrostomum lignano, a Model Organism for Evolutionary and Developmental Biology

    OpenAIRE

    Zadesenets, Kira S.; Vizoso, Dita B.; Schlatter, Aline; Konopatskaia, Irina D.; Berezikov, Eugene; Scharer, Lukas; Rubtsov, Nikolay B.

    2016-01-01

    Over the past decade, the free-living flatworm Macrostomum lignano has been successfully used in many areas of biology, including embryology, stem cells, sexual selection, bioadhesion and aging. The increased use of this powerful laboratory model, including the establishment of genomic resources and tools, makes it essential to have a detailed description of the chromosome organization of this species, previously suggested to have a karyotype with 2n = 8 and one pair of large and three pairs ...

  10. Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

    Science.gov (United States)

    Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

    2017-05-31

    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

  11. Stem thrust prediction model for W-K-M double wedge parallel expanding gate valves

    International Nuclear Information System (INIS)

    Eldiwany, B.; Alvarez, P.D.; Wolfe, K.

    1996-01-01

    An analytical model for determining the required valve stem thrust during opening and closing strokes of W-K-M parallel expanding gate valves was developed as part of the EPRI Motor-Operated Valve Performance Prediction Methodology (EPRI MOV PPM) Program. The model was validated against measured stem thrust data obtained from in-situ testing of three W-K-M valves. Model predictions show favorable, bounding agreement with the measured data for valves with Stellite 6 hardfacing on the disks and seat rings for water flow in the preferred flow direction (gate downstream). The maximum required thrust to open and to close the valve (excluding wedging and unwedging forces) occurs at a slightly open position and not at the fully closed position. In the nonpreferred flow direction, the model shows that premature wedging can occur during ΔP closure strokes even when the coefficients of friction at different sliding surfaces are within the typical range. This paper summarizes the model description and comparison against test data

  12. A novel zebrafish xenotransplantation model for study of glioma stem cell invasion.

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Yang

    Full Text Available Invasion and metastasis of solid tumors are the major causes of death in cancer patients. Cancer stem cells (CSCs constitute a small fraction of tumor cell population, but play a critical role in tumor invasion and metastasis. The xenograft of tumor cells in immunodeficient mice is one of commonly used in vivo models to study the invasion and metastasis of cancer cells. However, this model is time-consuming and labor intensive. Zebrafish (Danio rerio and their transparent embryos are emerging as a promising xenograft tumor model system for studies of tumor invasion. In this study, we established a tumor invasion model by using zebrafish embryo xenografted with human glioblastoma cell line U87 and its derived cancer stem cells (CSCs. We found that CSCs-enriched from U87 cells spreaded via the vessels within zebrafish embryos and such cells displayed an extremely high level of invasiveness which was associated with the up-regulated MMP-9 by CSCs. The invasion of glioma CSCs (GSCs in zebrafish embryos was markedly inhibited by an MMP-9 inhibitor. Thus, our zebrafish embryo model is considered a cost-effective approach tostudies of the mechanisms underlying the invasion of CSCs and suitable for high-throughput screening of novel anti-tumor invasion/metastasis agents.

  13. Stem thrust prediction model for W-K-M double wedge parallel expanding gate valves

    Energy Technology Data Exchange (ETDEWEB)

    Eldiwany, B.; Alvarez, P.D. [Kalsi Engineering Inc., Sugar Land, TX (United States); Wolfe, K. [Electric Power Research Institute, Palo Alto, CA (United States)

    1996-12-01

    An analytical model for determining the required valve stem thrust during opening and closing strokes of W-K-M parallel expanding gate valves was developed as part of the EPRI Motor-Operated Valve Performance Prediction Methodology (EPRI MOV PPM) Program. The model was validated against measured stem thrust data obtained from in-situ testing of three W-K-M valves. Model predictions show favorable, bounding agreement with the measured data for valves with Stellite 6 hardfacing on the disks and seat rings for water flow in the preferred flow direction (gate downstream). The maximum required thrust to open and to close the valve (excluding wedging and unwedging forces) occurs at a slightly open position and not at the fully closed position. In the nonpreferred flow direction, the model shows that premature wedging can occur during {Delta}P closure strokes even when the coefficients of friction at different sliding surfaces are within the typical range. This paper summarizes the model description and comparison against test data.

  14. Documentation on the development of the Swiss TIMES Electricity Model (STEM-E)

    International Nuclear Information System (INIS)

    Kannan, R.; Turton, H.

    2011-10-01

    This comprehensive report by the Paul Scherrer Institute PSI in Switzerland documents the development of the Swiss TIMES Electricity Model (STEM-E). This is a flexible model which explicitly depicts plausible pathways for the development of the Swiss electricity sector, while dealing with inter-temporal variations in demand and supply. TIMES is quoted as having the capability to portray the entire energy system from resource supply, through fuel processing, representation of infrastructures, conversion to secondary energy carriers, end-use technologies and energy service demands at end-use sectors. The background of the model's development and a reference energy system are described. Also, electricity end-use sectors and generating systems are examined, including hydropower, nuclear power, thermal generation and renewables. Environmental factors and the calibration of the model are discussed, as is the application of the model. The document is completed with an outlook, references and six appendices

  15. The damaging effect of densely ionizing radiations on stem cells of mammalian critical organs

    International Nuclear Information System (INIS)

    Konoplyannikov, A.G.; Konoplyannikova, O.A.

    1985-01-01

    Literature and experimental data on foundation of conceptions for cell determinants of survival rate in irradiated animals are analysed. Experimental confirmation of conceptions for cell determinants for both CFU of hemopoietic organs and for cases of intestinal death after densely ionizing radiation effect is obtained. The explanation of causes for difference in interrelation of two types of radiation death of animals in such a case is suggested

  16. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  17. The initiative on Model Organism Proteomes (iMOP) Session

    DEFF Research Database (Denmark)

    Schrimpf, Sabine P; Mering, Christian von; Bendixen, Emøke

    2012-01-01

    iMOP – the Initiative on Model Organism Proteomes – was accepted as a new HUPO initiative at the Ninth HUPO meeting in Sydney in 2010. A goal of iMOP is to integrate research groups working on a great diversity of species into a model organism community. At the Tenth HUPO meeting in Geneva...

  18. Competency modeling targeted on promotion of organizations towards VO involvement

    NARCIS (Netherlands)

    Ermilova, E.; Afsarmanesh, H.

    2008-01-01

    During the last decades, a number of models is introduced in research, addressing different perspectives of the organizations’ competencies in collaborative networks. This paper introduces the "4C-model", developed to address competencies of organizations, involved in Virtual organizations Breeding

  19. Modeling the Explicit Chemistry of Anthropogenic and Biogenic Organic Aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Madronich, Sasha [Univ. Corporation for Atmospheric Research, Boulder, CO (United States)

    2015-12-09

    The atmospheric burden of Secondary Organic Aerosols (SOA) remains one of the most important yet uncertain aspects of the radiative forcing of climate. This grant focused on improving our quantitative understanding of SOA formation and evolution, by developing, applying, and improving a highly detailed model of atmospheric organic chemistry, the Generation of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) model. Eleven (11) publications have resulted from this grant.

  20. Intestinal stem cells in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Jiang, Huaqi; Edgar, Bruce A.

    2011-01-01

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: ► The homeostasis and regeneration of adult fly midguts are mediated by ISCs. ► Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). ► EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. ► Notch signaling regulates ISC self-renewal and differentiation.

  1. Skeletal Muscle Regeneration in a Rat (Rattus norvegicus) Model with CorMatrix and Adipose Derived Stem Cells

    Science.gov (United States)

    2015-07-16

    Model with CorMatrix and Adipose Derived Stem Cells ." PRINCIPAL INVESTIGATOR (Pl) I TRAINING COORDINATOR (TC): Major Lucas Neff DEPARTMENT...ability of the matrix to work in concert with adipose derived stem cells for further augmentation of healing. 3 FDGXXX Attachments: Attachment 1...Introduction: The increasing use of explosive devices has led to a dramatic increase in traumatic injury accompanied by severe tissue trauma and

  2. Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models.

    Science.gov (United States)

    Sproul, Andrew A

    2015-01-01

    Human pluripotent stem cells (PSCs) have the capacity to revolutionize medicine by allowing the generation of functional cell types such as neurons for cell replacement therapy. However, the more immediate impact of PSCs on treatment of Alzheimer's disease (AD) will be through improved human AD model systems for mechanistic studies and therapeutic screening. This review will first briefly discuss different types of PSCs and genome-editing techniques that can be used to modify PSCs for disease modeling or for personalized medicine. This will be followed by a more in depth analysis of current AD iPSC models and a discussion of the need for more complex multicellular models, including cell types such as microglia. It will finish with a discussion on current clinical trials using PSC-derived cells and the long-term potential of such strategies for treating AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The export of mercury from Asia is studied by using the STEM-Hg model

    Science.gov (United States)

    Pan, L.; Carmichael, G.

    2005-12-01

    It is estimated that Asian countries (including China, India, and South and North Korea) contribute 56% to the global mercury emissions to the atmosphere due to the heavy use of coal. The large amount of mercury emissions and the long life time of mercury in the atmosphere imply the possibility of the long range transport of mercury from Asia to North America. To better understand the fate and transport of mercury between these two continents, the STEM-Hg model was developed based on up-to-date mercury mechanisms in the atmosphere. Mercury aqueous phase oxidation-reduction reactions, sulfite and oxygen aqueous phase reactions along with mercury gas phase reactions are included in the model. The model simulates Hg(0), Hg(2+) and Hg(p). By running the model using new mercury emissions inventory in two domains, the ACE-Asia and the ICARTT domains, the contributions of long range transport to Hg fluxes in North America are evaluated.

  4. Donor mesenchymal stem cells home to maternal wounds after transamniotic stem cell therapy (TRASCET) in a rodent model.

    Science.gov (United States)

    Graham, Christopher D; Shieh, Hester F; Brazzo, Joseph A; Zurakowski, David; Fauza, Dario O

    2017-06-01

    Transamniotic stem cell therapy (TRASCET) with amniotic fluid-derived MSCs (afMSCs) has emerged experimentally as a practical treatment strategy for congenital anomalies. In this study, we sought to determine whether afMSCs migrate to the mother following TRASCET. Pregnant rat dams were divided into three groups. Two groups received volume-matched injections into all amniotic cavities of either a suspension of afMSCs labeled with a luciferase reporter gene or the luciferase protein alone. In a third group, a suspension of labeled cells was aliquoted onto the serosal surface of the uterus. Maternal samples from the laparotomy scar (fascia and skin separately), bone marrow, and peripheral blood were procured, along with placenta and umbilical cord. Specimens were screened for luminescence via microplate luminometry. Luminescence was detected in 60% (9/15) of the fascial scars from the group receiving intraamniotic injection of afMSCs, but in none of the other groups (Pcells in the placenta and their presence in maternal fascia (Wald test=10.2; P=0.001). Amniotic mesenchymal stem cells migrate to maternal sites of injury after intraamniotic injection. Maternal homing of donor cells must be considered in the setting of transamniotic stem cell therapy. N/A (animal and laboratory study). Copyright © 2017 Elsevier Inc. All rights reserved.

  5. using stereochemistry models in teaching organic compounds

    African Journals Online (AJOL)

    Preferred Customer

    (Stereochemistry Model); the treatment had significant effect: students taught using. Stereochemistry Models ... ISSN 2227-5835. 93. Apart from the heavy conceptual demand on the memory capacity required of the ..... colors and sizes compared with the sketches on the chart that appear to be mock forms of the compounds.

  6. Paving the way towards complex blood-brain barrier models using pluripotent stem cells

    DEFF Research Database (Denmark)

    Lauschke, Karin; Frederiksen, Lise; Hall, Vanessa Jane

    2017-01-01

    to the unique tightness and selective permeability of the BBB and has been shown to be disrupted in many diseases and brain disorders, such as, vascular dementia, stroke, multiple sclerosis and Alzheimer's disease. Given the progress that pluripotent stem cells (PSCs) have made in the last two decades......A tissue with great need to be modelled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types (neurovascular unit (NVU)) that contribute...

  7. Saccharomyces cerevisiae as a model organism: a comparative study.

    Directory of Open Access Journals (Sweden)

    Hiren Karathia

    Full Text Available BACKGROUND: Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes. CONCLUSIONS/SIGNIFICANCE: The method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.

  8. Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ.

    Science.gov (United States)

    Thi-Kim Vu, Hanh; Rink, Jochen C; McKinney, Sean A; McClain, Melainia; Lakshmanaperumal, Naharajan; Alexander, Richard; Sánchez Alvarado, Alejandro

    2015-06-09

    Cystic kidney diseases (CKDs) affect millions of people worldwide. The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing, cell proliferation and differentiation. The underlying molecular mechanisms, however, remain poorly understood, and the derived excretory systems of established invertebrate models (Caenorhabditis elegans and Drosophila melanogaster) are unsuitable to model CKDs. Systematic structure/function comparisons revealed that the combination of ultrafiltration and flow-associated filtrate modification that is central to CKD etiology is remarkably conserved between the planarian excretory system and the vertebrate nephron. Consistently, both RNA-mediated genetic interference (RNAi) of planarian orthologues of human CKD genes and inhibition of tubule flow led to tubular cystogenesis that share many features with vertebrate CKDs, suggesting deep mechanistic conservation. Our results demonstrate a common evolutionary origin of animal excretory systems and establish planarians as a novel and experimentally accessible invertebrate model for the study of human kidney pathologies.

  9. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  10. Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    K. Naga Mohan

    2016-01-01

    Full Text Available Epigenetic mechanisms underlie differentiation of pluripotent stem cells into different lineages that contain identical genomes but express different sets of cell type-specific genes. Because of high discordance rates in monozygotic twins, epigenetic mechanisms are also implicated in development of neuropsychiatric disorders such as schizophrenia and autism. In support of this notion, increased levels of DNA methyltransferases (DNMTs, DNMT polymorphisms, and dysregulation of DNA methylation network were reported among schizophrenia patients. These results point to the importance of development of DNA methylation machinery-based models for studying the mechanism of abnormal neurogenesis due to certain DNMT alleles or dysregulated DNMTs. Achieving this goal is strongly confronted by embryonic lethality associated with altered levels of epigenetic machinery such as DNMT1 and expensive approaches in developing in vivo models. In light of literature evidence that embryonic stem cells (ESCs are tolerant of DNMT mutations and advancement in the technology of gene targeting, it is now possible to introduce desired mutations in DNMT loci to generate suitable ESC lines that can help understand the underlying mechanisms by which abnormal levels of DNMTs or their specific mutations/alleles result in abnormal neurogenesis. In the future, these models can facilitate development of suitable drugs for treatment of neuropsychiatric disorders.

  11. Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Faye M. Drawnel

    2014-11-01

    Full Text Available Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.

  12. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    Science.gov (United States)

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Induced Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Neurodegenerative Diseases.

    Science.gov (United States)

    Cao, Lei; Tan, Lan; Jiang, Teng; Zhu, Xi-Chen; Yu, Jin-Tai

    2015-08-01

    Although most neurodegenerative diseases have been closely related to aberrant accumulation of aggregation-prone proteins in neurons, understanding their pathogenesis remains incomplete, and there is no treatment to delay the onset or slow the progression of many neurodegenerative diseases. The availability of induced pluripotent stem cells (iPSCs) in recapitulating the phenotypes of several late-onset neurodegenerative diseases marks the new era in in vitro modeling. The iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in these diseases and provides a novel human stem cell platform for screening new candidate therapeutics. Modeling human diseases using iPSCs has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. In this review, we introduce iPSC-based disease modeling in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In addition, we discuss the implementation of iPSCs in drug discovery associated with some new techniques.

  14. Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

    Science.gov (United States)

    Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

    2018-05-01

    Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

  15. MODEL OF LEARNING ORGANIZATION IN BROADCASTING ORGANIZATION OF ISLAMIC REPUBLIC OF IRAN

    Directory of Open Access Journals (Sweden)

    Reza Najafbagy

    2010-11-01

    Full Text Available This article tries to present a model of learning organization for Iran Broadcasting Organization which is under the management of the spiritual leader of Iran. The study is based on characteristics of Peter Senge’s original learning organization namely, personal stery, mental models, shared vision, team learning and systems thinking. The methodology was a survey research employed questionnaire among sample employees and managers of the Organization.Findings showed that the Organization is fairly far from an ffective learning organization.Moreover, it seems that employees’ performance in team learning and changes in mental models are more satisfactory than managers. Regarding other characteristics of learning organizations, there are similarities in learning attempts by employees and managers. The rganization lacks organizational vision, and consequently there is no shared vision in the Organization. It also is in need of organizational culture. As a kind of state-owned organization, there s no need of financial support which affect the need for learning organization. It also does not face the threat of sustainabilitybecause there is no competitive organization.Findings also show that IBO need a fundamental change in its rganizational learning process. In this context, the general idea is to unfreeze the mindset of leadership of IBO and creating a visionand organizational culture based on learning and staff development. Then gradually through incremental effective change and continual organizational learning process in dividual, team and organization levels engage in development and reinforcement of skills of personal mastery, mental models, shared vision, team learning and systems thinking, should lead IBO to learning organization.

  16. Importance of Nongovernmental Organizations for the Establishment of a Successful Hematopoietic Stem-Cell Transplantation Program in a Developing Country

    Directory of Open Access Journals (Sweden)

    Monica M. Rivera Franco

    2018-02-01

    Full Text Available Purpose: In low- and middle-income countries with limited resources, the success of a hematopoietic stem-cell transplantation (HSCT program relies directly on its affordability while obtaining similar outcomes to developed regions. The objective of this study was to describe the experience of a tertiary/referral center in Mexico City performing HSCT with the subsidy of a nongovernmental organization (NGO. Patients and Methods: We performed a retrospective analysis including 146 patients who underwent HSCT at the National Institutes of Health Sciences and Nutrition Salvador Zubiran and were subsidized by the NGO Unidos. Results: Seventy-five patients (51% and 71 patients (49% underwent autologous and allogeneic HSCT, respectively. The median age was 30 years, 56% did not obtain a bachelor’s degree, 79% had a low socioeconomic level, and 75% were unemployed. None had any health coverage. According to the real patient out-of-pocket expense, the subsidy by Unidos corresponded to 88% and 72% in autologous and allogeneic HSCT, respectively. Conclusion: Our results highlight that undergoing an HSCT was feasible for vulnerable patients because of the subsidy of medications and chemotherapy by Unidos. Therefore, creating NGOs in developing countries is important to provide complex medical procedures, such as HSCT, at limited-resource centers to underserved populations while obtaining good outcomes.

  17. New directions for rabbit antithymocyte globulin (Thymoglobulin(®)) in solid organ transplants, stem cell transplants and autoimmunity.

    Science.gov (United States)

    Mohty, Mohamad; Bacigalupo, Andrea; Saliba, Faouzi; Zuckermann, Andreas; Morelon, Emmanuel; Lebranchu, Yvon

    2014-09-01

    In the 30 years since the rabbit antithymocyte globulin (rATG) Thymoglobulin(®) was first licensed, its use in solid organ transplantation and hematology has expanded progressively. Although the evidence base is incomplete, specific roles for rATG in organ transplant recipients using contemporary dosing strategies are now relatively well-identified. The addition of rATG induction to a standard triple or dual regimen reduces acute cellular rejection, and possibly humoral rejection. It is an appropriate first choice in patients with moderate or high immunological risk, and may be used in low-risk patients receiving a calcineurin inhibitor (CNI)-sparing regimen from time of transplant, or if early steroid withdrawal is planned. Kidney transplant patients at risk of delayed graft function may also benefit from the use of rATG to facilitate delayed CNI introduction. In hematopoietic stem cell transplantation, rATG has become an important component of conventional myeloablative conditioning regimens, following demonstration of reduced acute and chronic graft-versus-host disease. More recently, a role for rATG has also been established in reduced-intensity conditioning regimens. In autoimmunity, rATG contributes to the treatment of severe aplastic anemia, and has been incorporated in autograft projects for the management of conditions such as multiple sclerosis, Crohn's disease, and systemic sclerosis. Finally, research is underway for the induction of tolerance exploiting the ability of rATG to induce immunosuppresive cells such as regulatory T-cells. Despite its long history, rATG remains a key component of the immunosuppressive armamentarium, and its complex immunological properties indicate that its use will expand to a wider range of disease conditions in the future.

  18. Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

    Science.gov (United States)

    Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

    2016-01-01

    ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

  19. STEMS-Air: a simple GIS-based air pollution dispersion model for city-wide exposure assessment.

    Science.gov (United States)

    Gulliver, John; Briggs, David

    2011-05-15

    Current methods of air pollution modelling do not readily meet the needs of air pollution mapping for short-term (i.e. daily) exposure studies. The main limiting factor is that for those few models that couple with a GIS there are insufficient tools for directly mapping air pollution both at high spatial resolution and over large areas (e.g. city wide). A simple GIS-based air pollution model (STEMS-Air) has been developed for PM(10) to meet these needs with the option to choose different exposure averaging periods (e.g. daily and annual). STEMS-Air uses the grid-based FOCALSUM function in ArcGIS in conjunction with a fine grid of emission sources and basic information on meteorology to implement a simple Gaussian plume model of air pollution dispersion. STEMS-Air was developed and validated in London, UK, using data on concentrations of PM(10) from routinely available monitoring data. Results from the validation study show that STEMS-Air performs well in predicting both daily (at four sites) and annual (at 30 sites) concentrations of PM(10). For daily modelling, STEMS-Air achieved r(2) values in the range 0.19-0.43 (pplanning and management, or as the basis for health risk assessment and epidemiological studies. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  20. Modeling the influence of organic acids on soil weathering

    Science.gov (United States)

    Lawrence, Corey R.; Harden, Jennifer W.; Maher, Kate

    2014-01-01

    Biological inputs and organic matter cycling have long been regarded as important factors in the physical and chemical development of soils. In particular, the extent to which low molecular weight organic acids, such as oxalate, influence geochemical reactions has been widely studied. Although the effects of organic acids are diverse, there is strong evidence that organic acids accelerate the dissolution of some minerals. However, the influence of organic acids at the field-scale and over the timescales of soil development has not been evaluated in detail. In this study, a reactive-transport model of soil chemical weathering and pedogenic development was used to quantify the extent to which organic acid cycling controls mineral dissolution rates and long-term patterns of chemical weathering. Specifically, oxalic acid was added to simulations of soil development to investigate a well-studied chronosequence of soils near Santa Cruz, CA. The model formulation includes organic acid input, transport, decomposition, organic-metal aqueous complexation and mineral surface complexation in various combinations. Results suggest that although organic acid reactions accelerate mineral dissolution rates near the soil surface, the net response is an overall decrease in chemical weathering. Model results demonstrate the importance of organic acid input concentrations, fluid flow, decomposition and secondary mineral precipitation rates on the evolution of mineral weathering fronts. In particular, model soil profile evolution is sensitive to kaolinite precipitation and oxalate decomposition rates. The soil profile-scale modeling presented here provides insights into the influence of organic carbon cycling on soil weathering and pedogenesis and supports the need for further field-scale measurements of the flux and speciation of reactive organic compounds.

  1. Pathway Analysis and Modeling of the Differentiation of Human Embryonic Stem Cells into Hepatocyte-like Cells

    Science.gov (United States)

    Daskalaki, Andriani; Jozefczuk, Justyna; Lehrach, Hans; Adjaye, James; Wierling, Christoph

    2011-06-01

    A more detailed understanding of the differentiation of human embryonic and induced pluripotent stem cells into hepatocyte-like cells can help to improve therapies for liver diseases, like steatohepatitis. In this work we used microarray-based expression data to analyze the in vitro differentiation of human embryonic stem cells into hepatocytes. Pathway analysis has been carried out on gene expression data of different stages of the differentiation process from embryonic stem cells into hepatocyte-like cells via definitive endoderm and hepatic endoderm. Based on pathway analysis we identified signaling pathways, like the GPCR signaling pathway as well as FOXA2 regulatory networks. Based on these highly enriched pathways we constructed a model prototype to better understand and study the differentiation of stem cells into hepatocytes.

  2. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex...... growth of the U87 implants, but no invasion of cells into the brain tissue, neither in vitro nor in vivo. In contrast, SJ-1 was clearly invasive both in vitro and in vivo, but not very expansive. The co-cultures and brains with xenografts were immunohistochemically stained with anti-human vimentin...

  3. Daphnia as an Emerging Epigenetic Model Organism

    Directory of Open Access Journals (Sweden)

    Kami D. M. Harris

    2012-01-01

    Full Text Available Daphnia offer a variety of benefits for the study of epigenetics. Daphnia’s parthenogenetic life cycle allows the study of epigenetic effects in the absence of confounding genetic differences. Sex determination and sexual reproduction are epigenetically determined as are several other well-studied alternate phenotypes that arise in response to environmental stressors. Additionally, there is a large body of ecological literature available, recently complemented by the genome sequence of one species and transgenic technology. DNA methylation has been shown to be altered in response to toxicants and heavy metals, although investigation of other epigenetic mechanisms is only beginning. More thorough studies on DNA methylation as well as investigation of histone modifications and RNAi in sex determination and predator-induced defenses using this ecologically and evolutionarily important organism will contribute to our understanding of epigenetics.

  4. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  5. Mitochondrial resetting and metabolic reprogramming in induced pluripotent stem cells and mitochondrial disease modeling.

    Science.gov (United States)

    Hsu, Yi-Chao; Chen, Chien-Tsun; Wei, Yau-Huei

    2016-04-01

    Nuclear reprogramming with pluripotency factors enables somatic cells to gain the properties of embryonic stem cells. Mitochondrial resetting and metabolic reprogramming are suggested to be key early events in the induction of human skin fibroblasts to induced pluripotent stem cells (iPSCs). We review recent advances in the study of the molecular basis for mitochondrial resetting and metabolic reprogramming in the regulation of the formation of iPSCs. In particular, the recent progress in using iPSCs for mitochondrial disease modeling was discussed. iPSCs rely on glycolysis rather than oxidative phosphorylation as a major supply of energy. Mitochondrial resetting and metabolic reprogramming thus play crucial roles in the process of generation of iPSCs from somatic cells. Neurons, myocytes, and cardiomyocytes are cells containing abundant mitochondria in the human body, which can be differentiated from iPSCs or trans-differentiated from fibroblasts. Generating these cells from iPSCs derived from skin fibroblasts of patients with mitochondrial diseases or by trans-differentiation with cell-specific transcription factors will provide valuable insights into the role of mitochondrial DNA heteroplasmy in mitochondrial disease modeling and serves as a novel platform for screening of drugs to treat patients with mitochondrial diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model.

    Science.gov (United States)

    Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

    2015-01-01

    The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model.

  7. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

    Directory of Open Access Journals (Sweden)

    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  8. Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.

    Science.gov (United States)

    Crowell, Helena L; MacLean, Adam L; Stumpf, Michael P H

    2016-07-21

    Haematopoietic stem cell dynamics regulate healthy blood cell production and are disrupted during leukaemia. Competition models of cellular species help to elucidate stem cell dynamics in the bone marrow microenvironment (or niche), and to determine how these dynamics impact leukaemia progression. Here we develop two models that target acute myeloid leukaemia with particular focus on the mechanisms that control proliferation via feedback signalling. It is within regions of parameter space permissive of coexistence that the effects of competition are most subtle and the clinical outcome least certain. Steady state and linear stability analyses identify parameter regions that allow for coexistence to occur, and allow us to characterise behaviour near critical points. Where analytical expressions are no longer informative, we proceed statistically and sample parameter space over a coexistence region. We find that the rates of proliferation and differentiation of healthy progenitors exert key control over coexistence. We also show that inclusion of a regulatory feedback onto progenitor cells promotes healthy haematopoiesis at the expense of leukaemia, and that - somewhat paradoxically - within the coexistence region feedback increases the sensitivity of the system to dominance by one lineage over another. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Study of neuroprotective function of Ginkgo biloba extract (EGb761) derived-flavonoid monomers using a three-dimensional stem cell-derived neural model.

    Science.gov (United States)

    Wu, Yueting; Sun, Jiachen; George, Julian; Ye, Hua; Cui, Zhanfeng; Li, Zhaohui; Liu, Qingxi; Zhang, Yaozhou; Ge, Dan; Liu, Yang

    2016-05-01

    An in vitro three-dimensional (3D) cell culture system that can mimic organ and tissue structure and function in vivo will be of great benefit for drug discovery and toxicity testing. In this study, the neuroprotective properties of the three most prevalent flavonoid monomers extracted from EGb 761 (isorharmnetin, kaempferol, and quercetin) were investigated using the developed 3D stem cell-derived neural co-culture model. Rat neural stem cells were differentiated into co-culture of both neurons and astrocytes at an equal ratio in the developed 3D model and standard two-dimensional (2D) model using a two-step differentiation protocol for 14 days. The level of neuroprotective effect offered by each flavonoid was found to be aligned with its effect as an antioxidant and its ability to inhibit Caspase-3 activity in a dose-dependent manner. Cell exposure to quercetin (100 µM) following oxidative insult provided the highest levels of neuroprotection in both 2D and 3D models, comparable with exposure to 100 µM of Vitamin E, whilst exposure to isorhamnetin and kaempferol provided a reduced level of neuroprotection in both 2D and 3D models. At lower dosages (10 µM flavonoid concentration), the 3D model was more representative of results previously reported in vivo. The co-cultures of stem cell derived neurons and astrocytes in 3D hydrogel scaffolds as an in vitro neural model closely replicates in vivo results for routine neural drug toxicity and efficacy testing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:735-744, 2016. © 2016 American Institute of Chemical Engineers.

  10. Personality organization, five-factor model, and mental health.

    Science.gov (United States)

    Laverdière, Olivier; Gamache, Dominick; Diguer, Louis; Hébert, Etienne; Larochelle, Sébastien; Descôteaux, Jean

    2007-10-01

    Otto Kernberg has developed a model of personality and psychological functioning centered on the concept of personality organization. The purpose of this study is to empirically examine the relationships between this model, the five-factor model, and mental health. The Personality Organization Diagnostic Form (Diguer et al., The Personality Organization Diagnostic Form-II (PODF-II), 2001), the NEO Five-Factor Inventory (Costa and McCrae, Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) Professional Manual. 1992a), and the Health-Sickness Rating Scale (Luborsky, Arch Gen Psychiatry. 1962;7:407-417) were used to assess these constructs. Results show that personality organization and personality factors are distinct but interrelated constructs and that both contribute in similar proportion to mental health. Results also suggest that the integration of personality organization and factors can provide clinicians and researchers with an enriched understanding of psychological functioning.

  11. Designing a Composite Service Organization (Through Mathematical Modeling

    Directory of Open Access Journals (Sweden)

    Prof. Dr. A. Z. Memon

    2006-01-01

    Full Text Available Suppose we have a class of similar service organizations each of which is characterized by the same numerically measurable input/output characteristics. Even if the amount of any input does not differ in them, one or more organizations can be expected to outperform the others in one or more production aspects. Our interest lies in comparing the output efficiency levels of all service organizations. For it we use mathematical modeling, mainly linear programming to design a composite organization with new input measures which relative to a specific organization should have a higher level of efficiency with regard to all output measures. The other purpose of this paper is to evaluate the output characteristics of this proposed service organization. The paper also touches some other highly important planning features of this organization.

  12. Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

    Directory of Open Access Journals (Sweden)

    Christian Bucher

    2013-01-01

    Full Text Available Intervertebral disc (IVD cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5 by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

  13. Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models.

    Science.gov (United States)

    Shree, Nitya; Bhonde, Ramesh R

    2017-08-01

    The link between insulin resistance (IR) and type 2 diabetes has been recognized for a long time. Type 2 diabetes is often associated with basal hyperinsulinemia, reduced sensitivity to insulin, and disturbances in insulin release. There are evidences showing the reversal of IR by mesenchymal stem cells. However, the effect of conditioned media from adipose derived mesenchymal stem cells (ADSCs-CM) in reversal of IR has not been established. We established an insulin resistant model of 3T3L1 and C2C12 cells and treated with ADSCs-CM. 2-NBDG (2-[N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]Amino]-2-Deoxyglucose) uptake was performed to assess improvement in glucose uptake. Genes involved in glucose transport and in inflammation were also analysed. Western blot for glucose transporter-4 and Akt was performed to evaluate translocation of Glut4 and insulin signaling respectively. We found that the ADSCs-CM treated cells restored insulin, stimulated glucose uptake as compared to the untreated control indicating the insulin sensitizing effect of the CM. The treated cells also showed inhibition adipogenesis in 3T3L1 cells and significant reduction of intramuscular triglyceride accumulation in C2C12 cells. Gene expressions studies revealed the drastic upregulation of GLUT4 gene and significant reduction in IL6 and PAI1 gene in both 3T3L1 and C2C12 cells, indicating possible mechanism of glucose uptake with concomitant decrease in inflammation. Enhancement of GLUT4 and phospho Akt protein expression seems to be responsible for the increment in glucose uptake and enhanced insulin signaling, respectively. Our study revealed for the first time that ADSCs-CM acts as an alternative insulin sensitizer providing stem cell solution to IR. J. Cell. Biochem. 118: 2037-2043,2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Science.gov (United States)

    Ude, Chinedu C; Sulaiman, Shamsul B; Min-Hwei, Ng; Hui-Cheng, Chen; Ahmad, Johan; Yahaya, Norhamdan M; Saim, Aminuddin B; Idrus, Ruszymah B H

    2014-01-01

    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7) autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  15. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Directory of Open Access Journals (Sweden)

    Chinedu C Ude

    Full Text Available OBJECTIVES: In this study, Adipose stem cells (ADSC and bone marrow stem cells (BMSC, multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008. Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013. Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001. Fluorescence of the tracking dye (PKH26 in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  16. A Geoscience Workforce Model for Non-Geoscience and Non-Traditional STEM Students

    Science.gov (United States)

    Liou-Mark, J.; Blake, R.; Norouzi, H.; Vladutescu, D. V.; Yuen-Lau, L.

    2016-12-01

    The Summit on the Future of Geoscience Undergraduate Education has recently identified key professional skills, competencies, and conceptual understanding necessary in the development of undergraduate geoscience students (American Geosciences Institute, 2015). Through a comprehensive study involving a diverse range of the geoscience academic and employer community, the following professional scientist skills were rated highly important: 1) critical thinking/problem solving skills; 2) effective communication; 3) ability to access and integrate information; 4) strong quantitative skills; and 5) ability to work in interdisciplinary/cross cultural teams. Based on the findings of the study above, the New York City College of Technology (City Tech) has created a one-year intensive training program that focusses on the development of technical and non-technical geoscience skills for non-geoscience, non-traditional STEM students. Although City Tech does not offer geoscience degrees, the primary goal of the program is to create an unconventional pathway for under-represented minority STEM students to enter, participate, and compete in the geoscience workforce. The selected cohort of STEM students engage in year-round activities that include a geoscience course, enrichment training workshops, networking sessions, leadership development, research experiences, and summer internships at federal, local, and private geoscience facilities. These carefully designed programmatic elements provide both the geoscience knowledge and the non-technical professional skills that are essential for the geoscience workforce. Moreover, by executing this alternate, robust geoscience workforce model that attracts and prepares underrepresented minorities for geoscience careers, this unique pathway opens another corridor that helps to ameliorate the dire plight of the geoscience workforce shortage. This project is supported by NSF IUSE GEOPATH Grant # 1540721.

  17. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  18. Modeling the effects of temperature and relative humidity on gas exchange of prickly pear cactus (Opuntia spp.) stems

    NARCIS (Netherlands)

    Guevara-Arauza, J.C.; Yahia, E.M.; Cedeno, L.; Tijskens, L.M.M.

    2006-01-01

    A model to estimate gas profile of modified atmosphere packaged (MAP) prickly pear cactus stems was developed and calibrated. The model describes the transient gas exchange taking in consideration the effect of temperature (T) and relative humidity (RH) on film permeability (FPgas), respiration rate

  19. Neural Stem Cell or Human Induced Pluripotent Stem Cell-Derived GABA-ergic Progenitor Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy.

    Science.gov (United States)

    Upadhya, Dinesh; Hattiangady, Bharathi; Shetty, Geetha A; Zanirati, Gabriele; Kodali, Maheedhar; Shetty, Ashok K

    2016-08-17

    Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  20. (Tropical) soil organic matter modelling: problems and prospects

    NARCIS (Netherlands)

    Keulen, van H.

    2001-01-01

    Soil organic matter plays an important role in many physical, chemical and biological processes. However, the quantitative relations between the mineral and organic components of the soil and the relations with the vegetation are poorly understood. In such situations, the use of models is an

  1. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution. © 2015. Published by The Company of Biologists Ltd.

  2. Self-organizing map models of language acquisition

    Science.gov (United States)

    Li, Ping; Zhao, Xiaowei

    2013-01-01

    Connectionist models have had a profound impact on theories of language. While most early models were inspired by the classic parallel distributed processing architecture, recent models of language have explored various other types of models, including self-organizing models for language acquisition. In this paper, we aim at providing a review of the latter type of models, and highlight a number of simulation experiments that we have conducted based on these models. We show that self-organizing connectionist models can provide significant insights into long-standing debates in both monolingual and bilingual language development. We suggest future directions in which these models can be extended, to better connect with behavioral and neural data, and to make clear predictions in testing relevant psycholinguistic theories. PMID:24312061

  3. Social organization in the Minority Game model

    Science.gov (United States)

    Slanina, František

    2000-10-01

    We study the role of imitation within the Minority Game model of market. The players can exchange information locally, which leads to formation of groups which act as if they were single players. Coherent spatial areas of rich and poor agents result. We found that the global effectivity is optimized at certain value of the imitation probability, which decreases with increasing memory length. The social tensions are suppressed for large imitation probability, but generally the requirements of high global effectivity and low social tensions are in conflict.

  4. Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

    Science.gov (United States)

    Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

    1998-01-01

    A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

  5. Modelling the self-organization and collapse of complex networks

    Indian Academy of Sciences (India)

    Modelling the self-organization and collapse of complex networks. Sanjay Jain Department of Physics and Astrophysics, University of Delhi Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore Santa Fe Institute, Santa Fe, New Mexico.

  6. How valuable are model organisms for transposable element studies?

    Science.gov (United States)

    Kidwell, M G; Evgen'ev, M B

    1999-01-01

    Model organisms have proved to be highly informative for many types of genetic studies involving 'conventional' genes. The results have often been successfully generalized to other closely related organisms and also, perhaps surprisingly frequently, to more distantly related organisms. Because of the wealth of previous knowledge and their availability and convenience, model organisms were often the species of choice for many of the earlier studies of transposable elements. The question arises whether the results of genetic studies of transposable elements in model organisms can be extrapolated in the same ways as those of conventional genes? A number of observations suggest that special care needs to be taken in generalizing the results from model organisms to other species. A hallmark of many transposable elements is their ability to amplify rapidly in species genomes. Rapid spread of a newly invaded element throughout a species range has also been demonstrated. The types and genomic copy numbers of transposable elements have been shown to differ greatly between some closely related species. Horizontal transfer of transposable elements appears to be more frequent than for nonmobile genes. Furthermore, the population structure of some model organisms has been subject to drastic recent changes that may have some bearing on their transposable element genomic complements. In order to initiate discussion of this question, several case studies of transposable elements in well-studied Drosophila species are presented.

  7. Labour Quality Model for Organic Farming Food Chains

    OpenAIRE

    Gassner, B.; Freyer, B.; Leitner, H.

    2008-01-01

    The debate on labour quality in science is controversial as well as in the organic agriculture community. Therefore, we reviewed literature on different labour quality models and definitions, and had key informant interviews on labour quality issues with stakeholders in a regional oriented organic agriculture bread food chain. We developed a labour quality model with nine quality categories and discussed linkages to labour satisfaction, ethical values and IFOAM principles.

  8. Business Model Innovation in Incumbent Organizations: : Challenges and Success Routes

    OpenAIRE

    Salama, Ahmad; Parvez, Khawar

    2015-01-01

    In this thesis major challenges of creating business models at incumbents within mature industries are identified along with a mitigation plan. Pressure is upon incumbent organizations in order to keep up with the latest rapid technological advancements, the launching of startups that almost cover every field of business and the continuous change in customers’ tastes and needs. That along with various factors either forced organizations to continually reevaluate their current business models ...

  9. Reverse Osmosis Processing of Organic Model Compounds and Fermentation Broths

    Science.gov (United States)

    2006-04-01

    key species found in the fermentation broth: ethanol, butanol, acetic acid, oxalic acid, lactic acid, and butyric acid. Correlations of the rejection...AFRL-ML-TY-TP-2007-4545 POSTPRINT REVERSE OSMOSIS PROCESSING OF ORGANIC MODEL COMPOUNDS AND FERMENTATION BROTHS Robert Diltz...TELEPHONE NUMBER (Include area code) Bioresource Technology 98 (2007) 686–695Reverse osmosis processing of organic model compounds and fermentation broths

  10. On the Relationship between Aquatic Plant Stem Characteristics and Drag Force: Is a Modeling Application Possible?

    Directory of Open Access Journals (Sweden)

    Anna Maria Łoboda

    2018-04-01

    Full Text Available This paper presents a basic model that shows the relationship between the diameter of a stem and its flexural rigidity. The model was developed from experimental measurements of biomechanical traits (i.e., tensile and bending traits like maximum forces, stresses, moduli of elasticity, flexural rigidity, strain of three freshwater macrophyte species (Elodea canadensis Michx., Potamogeton pectinatus L., and P. crispus L., reflecting the seasonal changes in plant biomechanics throughout the vegetative season. These were obtained with the use of a bench-top testing machine in 2016 and 2017. The presented calculations are based on the ratio of drag-to-bending forces, in which the flexural rigidity plays a key role. The proposed model has the form EI = adb, and two approaches based on a regression analysis were applied to determine the parameters of the model—a and b. In the first method, the parameters were identified separately for each day of measurement, while in the second method, the coefficient b was calculated for all data from all days as a unified number for individual plants. The results suggest that coefficient b may provide information about the proportion of changes in drag forces depending on plant stiffness. The values of this coefficient were associated with the shape of the stem cross-section. The more circular the cross-section, the closer the value of the parameter was to 1. The parameter values were 1.60 for E. canadensis, 1.98 for P. pectinatus, and 2.46 for P. crispus. Moreover, this value also depended on the density of the cross-section structure. Most of the results showed that with an increase in stem diameter, the ratio between the drag and bending forces decreased, which led to fewer differences between these two forces. The model application may be introduced in many laboratory measurements of flow–biota interactions as well as in aquatic plant management applications. The implementation of these results in control

  11. Collaboration of 3D context and extracellular matrix in the development of glioma stemness in a 3D model.

    Science.gov (United States)

    Ma, Nina K L; Lim, Jia Kai; Leong, Meng Fatt; Sandanaraj, Edwin; Ang, Beng Ti; Tang, Carol; Wan, Andrew C A

    2016-02-01

    A hierarchy of cellular stemness exists in certain cancers, and any successful strategy to treat such cancers would have to eliminate the self-renewing tumor-initiating cells at the apex of the hierarchy. The cellular microenvironment, in particular the extracellular matrix (ECM), is believed to have a role in regulating stemness. In this work, U251 glioblastoma cells are cultured on electrospun polystyrene (ESPS) scaffolds coated with an array of 7 laminin isoforms to provide a 3D model for stem cell-related genes and proteins expression studies. We observed collaboration between 3D context and laminins in promoting glioma stemness. Depending on the laminin isoform presented, U251 cells cultured on ESPS scaffolds (3D) exhibited increased expression of stemness markers compared to those cultured on tissue culture polystyrene (2D). Our results indicate the influence of 3D (versus 2D) context on integrin expression, specifically, the upregulation of the laminin-binding integrins alpha 6 and beta 4. By a colony forming assay, we showed enhanced clonogenicity of cells grown on ESPS scaffolds in collaboration with laminins 411, 421, 511 and 521. Evaluation of patient glioma databases demonstrated significant enrichment of integrin and ECM pathway networks in tumors of worse prognosis, consistent with our observations. The present results demonstrate how 3D versus 2D context profoundly affects ECM signaling, leading to stemness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Intracutaneously injected human adipose tissue-derived stem cells in a mouse model stay at the site of injection.

    Science.gov (United States)

    Koellensperger, E; Lampe, K; Beierfuss, A; Gramley, F; Germann, G; Leimer, U

    2014-06-01

    The aim of this study was to evaluate the local behavior of intracutaneously injected human mesenchymal stem cells from adipose tissue and to determine the safety of a cell-based cutaneous therapy in an animal model.Human mesenchymal stem cells from adipose tissue were labeled with red fluorochrome and were injected intradermally in the paravertebral area in immunodeficient BalbC/nude mice (n = 21). As a control, cell culturemedium was injected in the same fashion on the contralateral paravertebral side. Four weeks, 6 months, and 12 months after the injection, seven mice were examined. In addition to the injected areas, the lungs, kidneys,spleens, and brains were excised and processed for histological evaluation. Serial sections of all the tissues excised were evaluated for adipose tissue-derived stem cells by means of emerging red fluorescent signals.The injected stem cells could be detected throughout the follow-up period of 1-year at the injection site within the dermal and subcutaneous layers. Bar these areas, adipose tissue-derived stem cells were not found in any otherexamined tissue at any point in time. The adipose tissue-derived stem cells showed a slow transition to deeper subcutaneous adipose tissue layers and, in part, a differentiation into adipocytes. No ulceration, inflammation, ortumor induction could be detected.The present study shows that intracutaneously injected human mesenchymal stem cells from adipose tissue stay at the site of injection, survive in vivo for up to 1-year, and partly differentiate into adipocytes. This is a new andvery important finding needed to safely apply therapies based on such stem cells in fat transplants in regenerative medicine. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research.

    Science.gov (United States)

    Engel, Martin; Do-Ha, Dzung; Muñoz, Sonia Sanz; Ooi, Lezanne

    2016-10-01

    Induced pluripotent stem cells and embryonic stem cells have revolutionized cellular neuroscience, providing the opportunity to model neurological diseases and test potential therapeutics in a pre-clinical setting. The power of these models has been widely discussed, but the potential pitfalls of stem cell differentiation in this research are less well described. We have analyzed the literature that describes differentiation of human pluripotent stem cells into three neural cell types that are commonly used to study diseases, including forebrain cholinergic neurons for Alzheimer's disease, midbrain dopaminergic neurons for Parkinson's disease and cortical astrocytes for neurodegenerative and psychiatric disorders. Published protocols for differentiation vary widely in the reported efficiency of target cell generation. Additionally, characterization of the cells by expression profile and functionality differs between studies and is often insufficient, leading to highly variable protocol outcomes. We have synthesized this information into a simple methodology that can be followed when performing or assessing differentiation techniques. Finally we propose three considerations for future research, including the use of physiological O2 conditions, three-dimensional co-culture systems and microfluidics to control feeding cycles and growth factor gradients. Following these guidelines will help researchers to ensure that robust and meaningful data is generated, enabling the full potential of stem cell differentiation for disease modeling and regenerative medicine.

  14. Neural stem cells for disease modeling of Wolman disease and evaluation of therapeutics.

    Science.gov (United States)

    Aguisanda, Francis; Yeh, Charles D; Chen, Catherine Z; Li, Rong; Beers, Jeanette; Zou, Jizhong; Thorne, Natasha; Zheng, Wei

    2017-06-28

    Wolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). Deficiency in LAL function causes accumulation of cholesteryl esters and triglycerides in lysosomes. Fatality usually occurs within the first year of life. While an enzyme replacement therapy has recently become available, there is currently no small-molecule drug treatment for WD. We have generated induced pluripotent stem cells (iPSCs) from two WD patient dermal fibroblast lines and subsequently differentiated them into neural stem cells (NSCs). The WD NSCs exhibited the hallmark disease phenotypes of neutral lipid accumulation, severely deficient LAL activity, and increased LysoTracker dye staining. Enzyme replacement treatment dramatically reduced the WD phenotype in these cells. In addition, δ-tocopherol (DT) and hydroxypropyl-beta-cyclodextrin (HPBCD) significantly reduced lysosomal size in WD NSCs, and an enhanced effect was observed in DT/HPBCD combination therapy. The results demonstrate that these WD NSCs are valid cell-based disease models with characteristic disease phenotypes that can be used to evaluate drug efficacy and screen compounds. DT and HPBCD both reduce LysoTracker dye staining in WD cells. The cells may be used to further dissect the pathology of WD, evaluate compound efficacy, and serve as a platform for high-throughput drug screening to identify new compounds for therapeutic development.

  15. NEW MODEL FOR QUANTIFICATION OF ICT DEPENDABLE ORGANIZATIONS RESILIENCE

    Directory of Open Access Journals (Sweden)

    Zora Arsovski

    2011-03-01

    Full Text Available Business environment today demands high reliable organizations in every segment to be competitive on the global market. Beside that, ICT sector is becoming irreplaceable in many fields of business, from the communication to the complex systems for process control and production. To fulfill those requirements and to develop further, many organizations worldwide are implementing business paradigm called - organizations resilience. Although resilience is well known term in many science fields, it is not well studied due to its complex nature. This paper is dealing with developing the new model for assessment and quantification of ICT dependable organizations resilience.

  16. Knowledge Loss: A Defensive Model In Nuclear Research Organization Memory

    International Nuclear Information System (INIS)

    Mohamad Safuan Bin Sulaiman; Muhd Noor Muhd Yunus

    2013-01-01

    Knowledge is an essential part of research based organization. It should be properly managed to ensure that any pitfalls of knowledge retention due to knowledge loss of both tacit and explicit is mitigated. Audit of the knowledge entities exist in the organization is important to identify the size of critical knowledge. It is very much related to how much know-what, know-how and know-why experts exist in the organization. This study conceptually proposed a defensive model for Nuclear Malaysia's organization memory and application of Knowledge Loss Risk Assessment (KLRA) as an important tool for critical knowledge identification. (author)

  17. Mesenchymal stem cell therapy regenerates the native bone-tendon junction after surgical repair in a degenerative rat model.

    Directory of Open Access Journals (Sweden)

    Geoffroy Nourissat

    Full Text Available BACKGROUND: The enthesis, which attaches the tendon to the bone, naturally disappears with aging, thus limiting joint mobility. Surgery is frequently needed but the clinical outcome is often poor due to the decreased natural healing capacity of the elderly. This study explored the benefits of a treatment based on injecting chondrocyte and mesenchymal stem cells (MSC in a new rat model of degenerative enthesis repair. METHODOLOGY: The Achilles' tendon was cut and the enthesis destroyed. The damage was repaired by classical surgery without cell injection (group G1, n = 52 and with chondrocyte (group G2, n = 51 or MSC injection (group G3, n = 39. The healing rate was determined macroscopically 15, 30 and 45 days later. The production and organization of a new enthesis was assessed by histological scoring of collagen II immunostaining, glycoaminoglycan production and the presence of columnar chondrocytes. The biomechanical load required to rupture the bone-tendon junction was determined. PRINCIPAL FINDINGS: The spontaneous healing rate in the G1 control group was 40%, close to those observed in humans. Cell injection significantly improved healing (69%, p = 0.0028 for G2 and p = 0.006 for G3 and the load-to-failure after 45 days (p<0.05 over controls. A new enthesis was clearly produced in cell-injected G2 and G3 rats, but not in the controls. Only the MSC-injected G3 rats had an organized enthesis with columnar chondrocytes as in a native enthesis 45 days after surgery. CONCLUSIONS: Cell therapy is an efficient procedure for reconstructing degenerative entheses. MSC treatment produced better organ regeneration than chondrocyte treatment. The morphological and biomechanical properties were similar to those of a native enthesis.

  18. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z

    2013-07-01

    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  19. Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model

    OpenAIRE

    Yousefifard, Mahmoud; Nasirinezhad, Farinaz; Shardi Manaheji, Homa; Janzadeh, Atousa; Hosseini, Mostafa; Keshavarz, Mansoor

    2016-01-01

    Background Stem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief. Methods A compression model was used to induce SCI in a rat model. A w...

  20. Using induced pluripotent stem cells derived neurons to model brain diseases

    Directory of Open Access Journals (Sweden)

    Cindy E McKinney

    2017-01-01

    Full Text Available The ability to use induced pluripotent stem cells (iPSC to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

  1. Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates.

    Directory of Open Access Journals (Sweden)

    Mark D Ungrin

    Full Text Available BACKGROUND: Human embryonic stem cells (hESC should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB] typically employed to reveal hESC developmental potential are heterogeneous and exhibit disorganized differentiation, progress in hESC technology development has been hindered. METHODOLOGY/PRINCIPAL FINDINGS: Using a centrifugal forced-aggregation strategy in combination with a novel centrifugal-extraction approach as a foundation, we demonstrated that hESC input composition and inductive environment could be manipulated to form large numbers of well-defined aggregates exhibiting multi-lineage differentiation and substantially improved self-organization from single-cell suspensions. These aggregates exhibited coordinated bi-domain structures including contiguous regions of extraembryonic endoderm- and epiblast-like tissue. A silicon wafer-based microfabrication technology was used to generate surfaces that permit the production of hundreds to thousands of hEB per cm(2. CONCLUSIONS/SIGNIFICANCE: The mechanisms of early human embryogenesis are poorly understood. We report an ultra high throughput (UHTP approach for generating spatially and temporally synchronised hEB. Aggregates generated in this manner exhibited aspects of peri-implantation tissue-level morphogenesis. These results should advance fundamental studies into early human developmental processes, enable high-throughput screening strategies to identify conditions that specify hESC-derived cells and tissues, and accelerate the pre-clinical evaluation of hESC-derived cells.

  2. Influence of dissolved organic carbon content on modelling natural organic matter acid-base properties.

    Science.gov (United States)

    Garnier, Cédric; Mounier, Stéphane; Benaïm, Jean Yves

    2004-10-01

    Natural organic matter (NOM) behaviour towards proton is an important parameter to understand NOM fate in the environment. Moreover, it is necessary to determine NOM acid-base properties before investigating trace metals complexation by natural organic matter. This work focuses on the possibility to determine these acid-base properties by accurate and simple titrations, even at low organic matter concentrations. So, the experiments were conducted on concentrated and diluted solutions of extracted humic and fulvic acid from Laurentian River, on concentrated and diluted model solutions of well-known simple molecules (acetic and phenolic acids), and on natural samples from the Seine river (France) which are not pre-concentrated. Titration experiments were modelled by a 6 acidic-sites discrete model, except for the model solutions. The modelling software used, called PROSECE (Programme d'Optimisation et de SpEciation Chimique dans l'Environnement), has been developed in our laboratory, is based on the mass balance equilibrium resolution. The results obtained on extracted organic matter and model solutions point out a threshold value for a confident determination of the studied organic matter acid-base properties. They also show an aberrant decreasing carboxylic/phenolic ratio with increasing sample dilution. This shift is neither due to any conformational effect, since it is also observed on model solutions, nor to ionic strength variations which is controlled during all experiments. On the other hand, it could be the result of an electrode troubleshooting occurring at basic pH values, which effect is amplified at low total concentration of acidic sites. So, in our conditions, the limit for a correct modelling of NOM acid-base properties is defined as 0.04 meq of total analysed acidic sites concentration. As for the analysed natural samples, due to their high acidic sites content, it is possible to model their behaviour despite the low organic carbon concentration.

  3. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  4. Characterization of lung stem cell niches in a mouse model of bleomycin-induced fibrosis

    Science.gov (United States)

    2012-01-01

    Introduction In lung fibrosis, alveolar epithelium degenerates progressively. The goal of regenerative medicine is to aid repair and regeneration of the lost tissues in parenchyma and airways for which mobilization of tissue-resident endogenous or bone marrow-derived exogenous stem cells niches is a critical step. We used a lung injury model in mice to identify and characterize functional lung stem cells to clarify how stem cell niches counteract this degenerative process. Methods Short term assay (STA) - Bleomycin-induced lung inflammation and fibrosis were assessed in a model of idiopathic pulmonary fibrosis in wild-type (WT), gp91phox-/- (NOX-/-), and gp91phoxMMP-12 double knockout (DKO) mice on C57Bl/6 background and Hoechst 33322 dye effluxing side population (SP) cells characterized. Long term assay (LTA) - In a bleomycin induced lung fibrosis model in C57Bl6 mice, the number of mature cells were quantified over 7, 14, and 21 days in bone marrow (BM), peripheral blood (PB), lung parenchyma (LP) and brochoalveolar lavage (BAL) fluid by FACS. BrdU pulse chase experiment (10 weeks) was used to identify label retaining cells (LRC). BrdU+ and BrdU- cells were characterized by hematopoietic (CD45+), pluripotency (TTF1+, Oct3/4+, SSEA-3+, SSEA-4+, Sca1+, Lin-, CD34+, CD31+), and lung lineage-specific (SPC+, AQP-5+, CC-10+) markers. Clonogenic potential of LRCs were measured by CFU-c assays. Results STA- In lung, cellularity increased by 5-fold in WT and 6-fold in NOX-/- by d7. Lung epithelial markers were very low in expression in all SP flow sorted from lung of all three genotypes cultured ex vivo. (p bleomycin, the SP in NOX-/- lung increased by 3.6-fold over WT where it increased by 20-fold over controls. Type I and II alveolar epithelial cells progressively diminished in all three genotypes by d21 post-bleomycin. D7 post-bleomycin, CD45+ cells in BALf in NOX-/- was 1.7-fold > WT, 57% of which were Mf that decreased by 67% in WT and 83% in NOX-/- by d21.LTA

  5. Genomic resources for the flatworm model organism Macrostomum lignano

    NARCIS (Netherlands)

    Simanov, D.

    2014-01-01

    The last two decades were marked by discoveries and breakthroughs in different biological disciplines, and stem cell biology is an example of the quickly developing field. Discovery of stem cell niches and successful reprogramming of somatic cells into pluripotent stem state are only a few step

  6. Drosophila melanogaster as a model organism to study nanotoxicity.

    Science.gov (United States)

    Ong, Cynthia; Yung, Lin-Yue Lanry; Cai, Yu; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2015-05-01

    Drosophila melanogaster has been used as an in vivo model organism for the study of genetics and development since 100 years ago. Recently, the fruit fly Drosophila was also developed as an in vivo model organism for toxicology studies, in particular, the field of nanotoxicity. The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited due to high operational cost and ethical objections. Hence, Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity. This review discusses the basic biology of Drosophila, the toxicity of nanomaterials, as well as how the Drosophila model can be used to study the toxicity of various types of nanomaterials.

  7. Investigating ecological speciation in non-model organisms

    DEFF Research Database (Denmark)

    Foote, Andrew David

    2012-01-01

    on killer whale evolutionary ecology in search of any difficulty in demonstrating causal links between variation in phenotype, ecology, and reproductive isolation in this non-model organism. Results: At present, we do not have enough evidence to conclude that adaptive phenotype traits linked to ecological...... speciation in non-model organisms that lead to this bias? What alternative approaches might redress the balance? Organism: Genetically differentiated types of the killer whale (Orcinus orca) exhibiting differences in prey preference, habitat use, morphology, and behaviour. Methods: Review of the literature...... variation underlie reproductive isolation between sympatric killer whale types. Perhaps ecological speciation has occurred, but it is hard to prove. We will probably face this outcome whenever we wish to address non-model organisms – species in which it is not easy to apply experimental approaches...

  8. Modelling the fate of oxidisable organic contaminants in groundwater

    DEFF Research Database (Denmark)

    Barry, D.A.; Prommer, H.; Miller, C.T.

    2002-01-01

    modelling framework is illustrated by pertinent examples, showing the degradation of dissolved organics by microbial activity limited by the availability of nutrients or electron acceptors (i.e., changing redox states), as well as concomitant secondary reactions. Two field-scale modelling examples...... are discussed, the Vejen landfill (Denmark) and an example where metal contamination is remediated by redox changes wrought by injection of a dissolved organic compound. A summary is provided of current and likely future challenges to modelling of oxidisable organics in the subsurface. (C) 2002 Elsevier Science......Subsurface contamination by organic chemicals is a pervasive environmental problem, susceptible to remediation by natural or enhanced attenuation approaches or more highly engineered methods such as pump-and-treat, amongst others. Such remediation approaches, along with risk assessment...

  9. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Erin C. Hedges

    2016-01-01

    Full Text Available In recent years several genes have linked amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

  10. A bioengineered murine model using CD24+CD44+ pancreatic cancer stem cells for chemotherapy study

    International Nuclear Information System (INIS)

    Qin, Shengqi; Li, Jianshe; Zhang, Zhongtao; Deng, Yiming

    2015-01-01

    In this work we first developed a murine pancreatic tumor model using CD24 + CD44 + pancreatic cancer stem cells (CSC) supported by an electrospun scaffold. Unlike conventional models, the use of CSC and the scaffold, which were biologically and chemically defined, afforded scientists a reliable platform to evaluate novel chemotherapy regimens. CD24 + CD44 + CSC successfully initiated tumorigenesis in vitro on the scaffold without suffering apoptosis, evidencing the lack of cytotoxicity of scaffolding materials. Also, the scaffold contributed to the acceleration of in vivo tumorigenesis and increased the likelihood of tumor formation. Using this model, we set out to explore the effectiveness of irinotecan/gemcitabine (IRIN-GEM), a chemotherapy regimen, for pancreatic cancer. Our study showed that IRIN-GEM induced a tumor regression whereas gemcitabine alone could only arrest the tumor growth. Further study suggested that the superior performance of IRIN-GEM could be attributed to its capacity to demolish the CD24 + CD44 + CSC sub-population by inducing a large-scale apoptosis. The use of highly proliferative yet homogenous CD24 + CD44 + CSC along with a chemically defined scaffold accelerated the tumor formation and significantly reduced the variability associated with conventional murine models. Armed with this new model, we discovered that IRIN-GEM would be a promising chemotherapy candidate for patients with advanced pancreatic cancer. (paper)

  11. Ecophysiological modeling of photosynthesis and carbon allocation to the tree stem in the boreal forest

    Directory of Open Access Journals (Sweden)

    F. Gennaretti

    2017-11-01

    Full Text Available A better understanding of the coupling between photosynthesis and carbon allocation in the boreal forest, together with its associated environmental factors and mechanistic rules, is crucial to accurately predict boreal forest carbon stocks and fluxes, which are significant components of the global carbon budget. Here, we adapted the MAIDEN ecophysiological forest model to consider important processes for boreal tree species, such as nonlinear acclimation of photosynthesis to temperature changes, canopy development as a function of previous-year climate variables influencing bud formation and the temperature dependence of carbon partition in summer. We tested these modifications in the eastern Canadian taiga using black spruce (Picea mariana (Mill. B.S.P. gross primary production and ring width data. MAIDEN explains 90 % of the observed daily gross primary production variability, 73 % of the annual ring width variability and 20–30 % of its high-frequency component (i.e., when decadal trends are removed. The positive effect on stem growth due to climate warming over the last several decades is well captured by the model. In addition, we illustrate how we improve the model with each introduced model adaptation and compare the model results with those of linear response functions. Our results demonstrate that MAIDEN simulates robust relationships with the most important climate variables (those detected by classical response-function analysis and is a powerful tool for understanding how environmental factors interact with black spruce ecophysiology to influence present-day and future boreal forest carbon fluxes.

  12. Ecophysiological modeling of photosynthesis and carbon allocation to the tree stem in the boreal forest

    Science.gov (United States)

    Gennaretti, Fabio; Gea-Izquierdo, Guillermo; Boucher, Etienne; Berninger, Frank; Arseneault, Dominique; Guiot, Joel

    2017-11-01

    A better understanding of the coupling between photosynthesis and carbon allocation in the boreal forest, together with its associated environmental factors and mechanistic rules, is crucial to accurately predict boreal forest carbon stocks and fluxes, which are significant components of the global carbon budget. Here, we adapted the MAIDEN ecophysiological forest model to consider important processes for boreal tree species, such as nonlinear acclimation of photosynthesis to temperature changes, canopy development as a function of previous-year climate variables influencing bud formation and the temperature dependence of carbon partition in summer. We tested these modifications in the eastern Canadian taiga using black spruce (Picea mariana (Mill.) B.S.P.) gross primary production and ring width data. MAIDEN explains 90 % of the observed daily gross primary production variability, 73 % of the annual ring width variability and 20-30 % of its high-frequency component (i.e., when decadal trends are removed). The positive effect on stem growth due to climate warming over the last several decades is well captured by the model. In addition, we illustrate how we improve the model with each introduced model adaptation and compare the model results with those of linear response functions. Our results demonstrate that MAIDEN simulates robust relationships with the most important climate variables (those detected by classical response-function analysis) and is a powerful tool for understanding how environmental factors interact with black spruce ecophysiology to influence present-day and future boreal forest carbon fluxes.

  13. Organism-level models: When mechanisms and statistics fail us

    Science.gov (United States)

    Phillips, M. H.; Meyer, J.; Smith, W. P.; Rockhill, J. K.

    2014-03-01

    Purpose: To describe the unique characteristics of models that represent the entire course of radiation therapy at the organism level and to highlight the uses to which such models can be put. Methods: At the level of an organism, traditional model-building runs into severe difficulties. We do not have sufficient knowledge to devise a complete biochemistry-based model. Statistical model-building fails due to the vast number of variables and the inability to control many of them in any meaningful way. Finally, building surrogate models, such as animal-based models, can result in excluding some of the most critical variables. Bayesian probabilistic models (Bayesian networks) provide a useful alternative that have the advantages of being mathematically rigorous, incorporating the knowledge that we do have, and being practical. Results: Bayesian networks representing radiation therapy pathways for prostate cancer and head & neck cancer were used to highlight the important aspects of such models and some techniques of model-building. A more specific model representing the treatment of occult lymph nodes in head & neck cancer were provided as an example of how such a model can inform clinical decisions. A model of the possible role of PET imaging in brain cancer was used to illustrate the means by which clinical trials can be modelled in order to come up with a trial design that will have meaningful outcomes. Conclusions: Probabilistic models are currently the most useful approach to representing the entire therapy outcome process.

  14. Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

    Directory of Open Access Journals (Sweden)

    Timothy M. Pierpont

    2017-11-01

    Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

  15. Modelling Human Channelopathies Using Induced Pluripotent Stem Cells: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Martin Müller

    2013-01-01

    Full Text Available The generation of induced pluripotent stem cells (iPS cells has pioneered the field of regenerative medicine and developmental biology. They can be generated by overexpression of a defined set of transcription factors in somatic cells derived from easily accessible tissues such as skin or plucked hair or even human urine. In case of applying this tool to patients who are classified into a disease group, it enables the generation of a disease- and patient-specific research platform. iPS cells have proven a significant tool to elucidate pathophysiological mechanisms in various diseases such as diabetes, blood disorders, defined neurological disorders, and genetic liver disease. One of the first successfully modelled human diseases was long QT syndrome, an inherited cardiac channelopathy which causes potentially fatal cardiac arrhythmia. This review summarizes the efforts of reprogramming various types of long QT syndrome and discusses the potential underlying mechanisms and their application.

  16. A Framework for Formal Modeling and Analysis of Organizations

    NARCIS (Netherlands)

    Jonker, C.M.; Sharpanskykh, O.; Treur, J.; P., Yolum

    2007-01-01

    A new, formal, role-based, framework for modeling and analyzing both real world and artificial organizations is introduced. It exploits static and dynamic properties of the organizational model and includes the (frequently ignored) environment. The transition is described from a generic framework of

  17. Spatial arrangement of organic compounds on a model mineral surface: implications for soil organic matter stabilization.

    Science.gov (United States)

    Petridis, Loukas; Ambaye, Haile; Jagadamma, Sindhu; Kilbey, S Michael; Lokitz, Bradley S; Lauter, Valeria; Mayes, Melanie A

    2014-01-01

    The complexity of the mineral-organic carbon interface may influence the extent of stabilization of organic carbon compounds in soils, which is important for global climate futures. The nanoscale structure of a model interface was examined here by depositing films of organic carbon compounds of contrasting chemical character, hydrophilic glucose and amphiphilic stearic acid, onto a soil mineral analogue (Al2O3). Neutron reflectometry, a technique which provides depth-sensitive insight into the organization of the thin films, indicates that glucose molecules reside in a layer between Al2O3 and stearic acid, a result that was verified by water contact angle measurements. Molecular dynamics simulations reveal the thermodynamic driving force behind glucose partitioning on the mineral interface: The entropic penalty of confining the less mobile glucose on the mineral surface is lower than for stearic acid. The fundamental information obtained here helps rationalize how complex arrangements of organic carbon on soil mineral surfaces may arise.

  18. Xanthusbase: adapting wikipedia principles to a model organism database.

    Science.gov (United States)

    Arshinoff, Bradley I; Suen, Garret; Just, Eric M; Merchant, Sohel M; Kibbe, Warren A; Chisholm, Rex L; Welch, Roy D

    2007-01-01

    xanthusBase (http://www.xanthusbase.org) is the official model organism database (MOD) for the social bacterium Myxococcus xanthus. In many respects, M.xanthus represents the pioneer model organism (MO) for studying the genetic, biochemical, and mechanistic basis of prokaryotic multicellularity, a topic that has garnered considerable attention due to the significance of biofilms in both basic and applied microbiology research. To facilitate its utility, the design of xanthusBase incorporates open-source software, leveraging the cumulative experience made available through the Generic Model Organism Database (GMOD) project, MediaWiki (http://www.mediawiki.org), and dictyBase (http://www.dictybase.org), to create a MOD that is both highly useful and easily navigable. In addition, we have incorporated a unique Wikipedia-style curation model which exploits the internet's inherent interactivity, thus enabling M.xanthus and other myxobacterial researchers to contribute directly toward the ongoing genome annotation.

  19. Investigating ecological speciation in non-model organisms

    DEFF Research Database (Denmark)

    Foote, Andrew David

    2012-01-01

    Background: Studies of ecological speciation tend to focus on a few model biological systems. In contrast, few studies on non-model organisms have been able to infer ecological speciation as the underlying mechanism of evolutionary divergence. Questions: What are the pitfalls in studying ecological...... on killer whale evolutionary ecology in search of any difficulty in demonstrating causal links between variation in phenotype, ecology, and reproductive isolation in this non-model organism. Results: At present, we do not have enough evidence to conclude that adaptive phenotype traits linked to ecological...... variation underlie reproductive isolation between sympatric killer whale types. Perhaps ecological speciation has occurred, but it is hard to prove. We will probably face this outcome whenever we wish to address non-model organisms – species in which it is not easy to apply experimental approaches...

  20. Induced Pluripotent Stem Cells: Applications in regenerative medicine, disease modelling and drug discovery

    Directory of Open Access Journals (Sweden)

    Vimal kishor Singh

    2015-02-01

    Full Text Available Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. IPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells, and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases, NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modelled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modelling and gene therapy. The technique offers benefits over other

  1. A mathematical model of mechanotransduction reveals how mechanical memory regulates mesenchymal stem cell fate decisions.

    Science.gov (United States)

    Peng, Tao; Liu, Linan; MacLean, Adam L; Wong, Chi Wut; Zhao, Weian; Nie, Qing

    2017-05-16

    Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts. We study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates. We present a continuous model that is able to describe the cell fate transitions that occur during differentiation, and analyze its dynamics with tools from multistability, bifurcation, and cell fate landscape analysis, and via stochastic simulation. Whereas experimentally, memory has only been observed during osteogenic differentiation, this model predicts that memory regions can exist for each of the four MSC-derived cell lineages. We can predict the substrate stiffness ranges over which memory drives differentiation; these are directly testable in an experimental setting. Furthermore, we quantitatively predict how substrate stiffness and culture duration co-regulate the fate of a stem cell, and we find that the feedbacks from the differentiating MSC onto its substrate are critical to preserve mechanical memory. Strikingly, we show that re-seeding MSCs onto a sufficiently soft substrate increases the number of cell fates accessible. Control of MSC differentiation is crucial for the success of much-lauded regenerative therapies based on MSCs. We have predicted new memory regions that will directly impact this control, and have quantified the size of the memory region for osteoblasts, as well as the co-regulatory effects on cell fates of substrate stiffness and culture duration. Taken together, these results can be used to develop novel strategies to better control the fates of MSCs in vitro and following transplantation.

  2. A self-organized criticality model for plasma transport

    International Nuclear Information System (INIS)

    Carreras, B.A.; Newman, D.; Lynch, V.E.

    1996-01-01

    Many models of natural phenomena manifest the basic hypothesis of self-organized criticality (SOC). The SOC concept brings together the self-similarity on space and time scales that is common to many of these phenomena. The application of the SOC modelling concept to the plasma dynamics near marginal stability opens new possibilities of understanding issues such as Bohm scaling, profile consistency, broad band fluctuation spectra with universal characteristics and fast time scales. A model realization of self-organized criticality for plasma transport in a magnetic confinement device is presented. The model is based on subcritical resistive pressure-gradient-driven turbulence. Three-dimensional nonlinear calculations based on this model show the existence of transport under subcritical conditions. This model that includes fluctuation dynamics leads to results very similar to the running sandpile paradigm

  3. An Ising model for metal-organic frameworks

    Science.gov (United States)

    Höft, Nicolas; Horbach, Jürgen; Martín-Mayor, Victor; Seoane, Beatriz

    2017-08-01

    We present a three-dimensional Ising model where lines of equal spins are frozen such that they form an ordered framework structure. The frame spins impose an external field on the rest of the spins (active spins). We demonstrate that this "porous Ising model" can be seen as a minimal model for condensation transitions of gas molecules in metal-organic frameworks. Using Monte Carlo simulation techniques, we compare the phase behavior of a porous Ising model with that of a particle-based model for the condensation of methane (CH4) in the isoreticular metal-organic framework IRMOF-16. For both models, we find a line of first-order phase transitions that end in a critical point. We show that the critical behavior in both cases belongs to the 3D Ising universality class, in contrast to other phase transitions in confinement such as capillary condensation.

  4. Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells.

    Science.gov (United States)

    Lauschke, Karin; Frederiksen, Lise; Hall, Vanessa Jane

    2017-06-15

    A tissue with great need to be modeled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types [neurovascular unit (NVU)] that contribute to the unique tightness and selective permeability of the BBB and has been shown to be disrupted in many diseases and brain disorders, such as vascular dementia, stroke, multiple sclerosis, and Alzheimer's disease. Given the progress that pluripotent stem cells (PSCs) have made in the past two decades, it is now possible to produce many cell types from the BBB and even partially recapitulate this complex tissue in vitro. In this review, we summarize the most recent developments in PSC differentiation and modeling of the BBB. We also suggest how patient-specific human-induced PSCs could be used to model BBB dysfunction in the future. Lastly, we provide perspectives on how to improve production of the BBB in vitro, for example by improving pericyte differentiation protocols and by better modeling the NVU in the dish.

  5. Development of a 3D co-culture model using human stem ...

    Science.gov (United States)

    Morphogenetic tissue fusion is a critical and complex event in embryonic development and failure of this event leads to birth defects, such as cleft palate. Palatal fusion requires adhesion and subsequent dissolution of the medial epithelial layer of the mesenchymal palatal shelves, and is regulated by the growth factors EGF and TGFβ, and others, although the complete regulatory mechanism is not understood. Three dimensional (3D) organotypic models allow us to mimic the native architecture of human tissue to facilitate the study of tissue dynamics and their responses to developmental toxicants. Our goal was to develop and characterize a spheroidal model of palatal fusion to investigate the mechanisms regulating fusion with exposure to growth factors and chemicals in the ToxCast program known to disrupt this event. We present a spheroidal model using human umbilical-derived mesenchymal stem cells (hMSC) spheroid cores cultured for 13 days and then coated with MaxGel™ basement membrane and a layer of human progenitor epithelial keratinocytes (hPEK) (hMSC+hPEK spheroids). We characterized the growth, differentiation, proliferation and fusion activity of the model. Spheroid diameter was dependent on hMSC seeding density, size of the seeding wells, time in culture, and type of medium. hMSC spheroid growth was enhanced with osteogenic differentiation medium. Alkaline phosphatase activity in the hMSC spheroid, indicating osteogenic differentiation, increased in inte

  6. Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models.

    Science.gov (United States)

    Wang, Li; Zhang, Haiyan; Guan, Lixun; Zhao, Shasha; Gu, Zhenyang; Wei, Huaping; Gao, Zhe; Wang, Feiyan; Yang, Nan; Luo, Lan; Li, Yonghui; Wang, Lili; Liu, Daihong; Gao, Chunji

    2016-09-20

    A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10-9) and clinical scores (standardized mean difference = -3.60, 95% confidence interval -4.43 to -2.76, P = 3.61×10-17). In addition, MSCs conferred robust favorable prophylactic effects on aGVHD across recipient species, MSC doses, and administration times, but not MSC sources. Our meta-analysis showed that MSCs significantly prevented mortality and alleviated the clinical manifestations of aGVHD in animal models. These data support further clinical trials aimed at evaluating the efficacy of using MSCs to prevent aGVHD.

  7. Regional Persistent Organic Pollutants' Environmental Impact Assessment and Control Model

    Directory of Open Access Journals (Sweden)

    Jurgis Staniskis

    2008-10-01

    Full Text Available The sources of formation, environmental distribution and fate of persistent organic pollutants (POPs are increasingly seen as topics to be addressed and solved at the global scale. Therefore, there are already two international agreements concerning persistent organic pollutants: the Protocol of 1998 to the 1979 Convention on the Long-Range Transboundary Air Pollution on Persistent Organic Pollutants (Aarhus Protocol; and the Stockholm Convention on Persistent Organic Pollutants. For the assessment of environmental pollution of POPs, for the risk assessment, for the evaluation of new pollutants as potential candidates to be included in the POPs list of the Stokholmo or/and Aarhus Protocol, a set of different models are developed or under development. Multimedia models help describe and understand environmental processes leading to global contamination through POPs and actual risk to the environment and human health. However, there is a lack of the tools based on a systematic and integrated approach to POPs management difficulties in the region.

  8. Making Organisms Model Human Behavior: Situated Models in North-American Alcohol Research, 1950-onwards

    Science.gov (United States)

    Leonelli, Sabina; Ankeny, Rachel A.; Nelson, Nicole C.; Ramsden, Edmund

    2014-01-01

    Argument We examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, as often the case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied. PMID:25233743

  9. Making organisms model human behavior: situated models in North-American alcohol research, since 1950.

    Science.gov (United States)

    Ankeny, Rachel A; Leonelli, Sabina; Nelson, Nicole C; Ramsden, Edmund

    2014-09-01

    We examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, as often the case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied.

  10. Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Philip W. Brownjohn

    2017-04-01

    Full Text Available Summary: Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP processing and the accumulation of APP-derived amyloid β (Aβ peptides are key processes in Alzheimer's disease (AD. We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation. : In this article, Livesey and colleagues perform a phenotypic drug screen in a human stem cell model of Alzheimer's disease. The anthelminthic avermectins are identified as a family of compounds that increase the production of short Aβ peptides over longer more toxic Aβ forms. The effect is analogous to existing γ-secretase modulators, but is independent of the core γ-secretase complex. Keywords: neural stem cells, Alzheimer's disease, phenotypic screening, iPSCs, human neurons, dementia, Down syndrome, amyloid beta, ivermectin, selamectin

  11. Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

    Science.gov (United States)

    Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

  12. Extracts of adipose derived stem cells slows progression in the R6/2 model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wooseok Im

    Full Text Available Stem cell therapy is a promising treatment for incurable disorders including Huntington's disease (HD. Adipose-derived stem cell (ASC is an easily available source of stem cells. Since ASCs can be differentiated into nervous stem cells, it has clinically feasible potential for neurodegenerative disease. In addition, ASCs secrete various anti-apoptotic growth factors, which improve the symptoms of disease from transplanted ASCs. Thus, cell-free extracts of ASCs (ASCs-E could be a potential candidate for treatment of HD. Here, we investigated effects of ASCs-E on R6/2 HD mouse model and neuronal cells. In R6/2 HD model, injection of ASCs-E improved the performance in Rotarod test. ASCs-E also ameliorated striatal atrophy and mutant huntingtin aggregation in the striatum. In Western blot increased expressions of p-Akt, p-CREB and PGC1α were noted by injection of ASCs-E, when comparing to the R6/2 HD model. Neuro2A neuroblastoma cells treated with ASCs-E showed increased expression of p-CREB and PGC1α. In conclusion, ASCs-E delayed disease progression in animal model of HD by restoring of CREB-PGC1α pathway and could be a potential resource for treatment of HD.

  13. Two-Year Community: A 3+8 Model of Undergraduate Research for Community College STEM Majors

    Science.gov (United States)

    Leggett-Robinson, Pamela M.; Villa, Brandi C.; Mooring, Suazette Reid

    2015-01-01

    This article describes the implementation of an innovative undergraduate research model for students attending a two-year institution. It gives students an opportunity to engage in undergraduate research at nearby four-year institutions, which provides a foundation that allows them to successfully make the transition to STEM programs at the…

  14. MODELLING CONSUMERS' DEMAND FOR ORGANIC FOOD PRODUCTS: THE SWEDISH EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Manuchehr Irandoust

    2016-07-01

    Full Text Available This paper attempts to examine a few factors characterizing consumer preferences and behavior towards organic food products in the south of Sweden using a proportional odds model which captures the natural ordering of dependent variables and any inherent nonlinearities. The findings show that consumer's choice for organic food depends on perceived benefits of organic food (environment, health, and quality and consumer's perception and attitudes towards labelling system, message framing, and local origin. In addition, high willingness to pay and income level will increase the probability to buy organic food, while the cultural differences and socio-demographic characteristics have no effect on consumer behaviour and attitudes towards organic food products. Policy implications are offered.

  15. Modelization of tritium transfer into the organic compartments of algae

    International Nuclear Information System (INIS)

    Bonotto, S.; Gerber, G.B.; Arapis, G.; Kirchmann, R.

    1982-01-01

    Uptake of tritium oxide and its conversion into organic tritium was studied in four different types of algae with widely varying size and growth characteristics (Acetabularia acetabulum, Boergesenia forbesii, two strains of Chlamydomonas and Dunaliella bioculata). Water in the cell and the vacuales equilibrates rapidly with external tritium water. Tritium is actively incorporated into organically bound form as the organisms grow. During the stationary phase, incorporation of tritium is slow. There exists a discrimination against the incorporation of tritium into organically bound form. A model has been elaborated taking in account these different factors. It appears that transfer of organic tritium by algae growing near the sites of release would be significant only for actively growing algae. Algae growing slowly may, however, be useful as cumulative indicators of discontinuous tritium release. (author)

  16. Dilbert-Peter model of organization effectiveness: computer simulations

    OpenAIRE

    Sobkowicz, Pawel

    2010-01-01

    We describe a computer model of general effectiveness of a hierarchical organization depending on two main aspects: effects of promotion to managerial levels and efforts to self-promote of individual employees, reducing their actual productivity. The combination of judgment by appearance in the promotion to higher levels of hierarchy and the Peter Principle (which states that people are promoted to their level of incompetence) results in fast declines in effectiveness of the organization. The...

  17. Modeling nanostructure-enhanced light trapping in organic solar cells

    DEFF Research Database (Denmark)

    Adam, Jost

    A promising approach for improving the power conversion efficiencies of organic solar cells (OSCs) is by incorporating nanostructures in their thin film architecture to improve the light absorption in the device’s active polymer layers. Here, we present a modelling framework for the prediction....... Diffraction by fractal metallic supergratings. Optics Express, 15(24), 15628–15636 (2007) [3] Goszczak, A. J. et al. Nanoscale Aluminum dimples for light trapping in organic thin films (submitted)...

  18. Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells.

    Science.gov (United States)

    Iglesia, Rebeca Piatniczka; Prado, Mariana Brandão; Cruz, Lilian; Martins, Vilma Regina; Santos, Tiago Góss; Lopes, Marilene Hohmuth

    2017-04-17

    Glioblastoma (GBM), a highly aggressive brain tumor, contains a subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising target for GBM treatment. Our group identified the cellular prion protein (PrP C ) and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance. GSCs expressing different levels of PrP C were cultured as neurospheres with growth factors, and characterized with stem cells markers and adhesion molecules markers through immunofluorescence and flow cytometry. We than evaluated GSC self-renewal and proliferation by clonal density assays and BrdU incorporation, respectively, in front of recombinant HOP treatment, combined or not with a HOP peptide which mimics the PrP C binding site. Stable silencing of HOP was also performed in parental and/or PrP C -depleted cell populations, and proliferation in vitro and tumor growth in vivo were evaluated. Migration assays were performed on laminin-1 pre-coated glass. We observed that, when GBM cells are cultured as neurospheres, they express specific stemness markers such as CD133, CD15, Oct4, and SOX2; PrP C is upregulated compared to monolayer culture and co-localizes with CD133. PrP C silencing downregulates the expression of molecules associated with cancer stem cells, upregulates markers of cell differentiation and affects GSC self-renewal, pointing to a pivotal role for PrP C in the maintenance of GSCs. Exogenous HOP treatment increases proliferation and self-renewal of GSCs in a PrP C -dependent manner while HOP knockdown disturbs the proliferation process. In vivo, PrP C and/or HOP knockdown potently inhibits the growth of subcutaneously implanted glioblastoma cells. In addition, disruption of the PrP C -HOP complex by a HOP peptide, which mimics the PrP C binding site, affects GSC self

  19. 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.

  20. Ectocarpus: a model organism for the brown algae.

    Science.gov (United States)

    Coelho, Susana M; Scornet, Delphine; Rousvoal, Sylvie; Peters, Nick T; Dartevelle, Laurence; Peters, Akira F; Cock, J Mark

    2012-02-01

    The brown algae are an interesting group of organisms from several points of view. They are the dominant organisms in many coastal ecosystems, where they often form large, underwater forests. They also have an unusual evolutionary history, being members of the stramenopiles, which are very distantly related to well-studied animal and green plant models. As a consequence of this history, brown algae have evolved many novel features, for example in terms of their cell biology and metabolic pathways. They are also one of only a small number of eukaryotic groups to have independently evolved complex multicellularity. Despite these interesting features, the brown algae have remained a relatively poorly studied group. This situation has started to change over the last few years, however, with the emergence of the filamentous brown alga Ectocarpus as a model system that is amenable to the genomic and genetic approaches that have proved to be so powerful in more classical model organisms such as Drosophila and Arabidopsis.

  1. Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

  2. Adipose stem cells differentiated chondrocytes regenerate damaged cartilage in rat model of osteoarthritis.

    Science.gov (United States)

    Latief, Noreen; Raza, Fahad Ali; Bhatti, Fazal-Ur-Rehman; Tarar, Moazzam Nazir; Khan, Shaheen N; Riazuddin, Sheikh

    2016-05-01

    Transplantation of mesenchymal stem cells (MSCs) or autologous chondrocytes has been shown to repair damages to articular cartilage due to osteoarthritis (OA). However, survival of transplanted cells is considerably reduced in the osteoarthritic environment and it affects successful outcome of the transplantation of the cells. Differentiated chrondroytes derived from adipose stem cells have been proposed as an alternative source and our study investigated this possibility in rats. We investigated the regenerative potential of ADSCs and DCs in osteoarthritic environment in the repair of cartilage in rats. We found that ADSCs maintained fibroblast morphology in vitro and also expressed CD90 and CD29. Furthermore, ADSCs differentiated into chondrocytes, accompanied by increased level of proteoglycans and expression of chondrocytes specific genes, such as, Acan, and Col2a1. Histological examination of transplanted knee joints showed regeneration of cartilage tissue compared to control OA knee joints. Increase in gene expression for Acan, Col2a1 with concomitant decrease in the expression of Col1a1 suggested formation of hyaline like cartilage. A significant increase in differentiation index was observed in DCs and ADSCs transplanted knee joints (P = 0.0110 vs. P = 0.0429) when compared to that in OA control knee joints. Furthermore, transplanted DCs showed increased proliferation along with reduction in apoptosis as compared to untreated control. In conclusion, DCs showed better survival and regeneration potential as compared with ADSCs in rat model of OA and thus may serve a better option for regeneration of osteoarthritic cartilage. © 2016 International Federation for Cell Biology.

  3. Generation of induced Pluripotent Stem Cells as disease modelling of NLSDM.

    Science.gov (United States)

    Tavian, D; Missaglia, S; Castagnetta, M; Degiorgio, D; Pennisi, E M; Coleman, R A; Dell'Era, P; Mora, C; Angelini, C; Coviello, D A

    2017-05-01

    Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare defect of triacylglycerol metabolism, characterized by the abnormal storage of neutral lipid in organelles known as lipid droplets (LDs). The main clinical features are progressive myopathy and cardiomyopathy. The onset of NLSDM is caused by autosomal recessive mutations in the PNPLA2 gene, which encodes adipose triglyceride lipase (ATGL). Despite its name, this enzyme is present in a wide variety of cell types and catalyzes the first step in triacylglycerol lipolysis and the release of fatty acids. Here, we report the derivation of NLSDM-induced pluripotent stem cells (NLSDM-iPSCs) from fibroblasts of two patients carrying different PNPLA2 mutations. The first patient was homozygous for the c.541delAC, while the second was homozygous for the c.662G>C mutation in the PNPLA2 gene. We verified that the two types of NLSDM-iPSCs possessed properties of embryonic-like stem cells and could differentiate into the three germ layers in vitro. Immunofluorescence analysis revealed that iPSCs had an abnormal accumulation of triglycerides in LDs, the hallmark of NLSDM. Furthermore, NLSDM-iPSCs were deficient in long chain fatty acid lipolysis, when subjected to a pulse chase experiment with oleic acid. Collectively, these results demonstrate that NLSDM-iPSCs are a promising in vitro model to investigate disease mechanisms and screen drug compounds for NLSDM, a rare disease with few therapeutic options. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Modelling the fate of organic micropollutants in stormwater ponds

    DEFF Research Database (Denmark)

    Vezzaro, Luca; Eriksson, Eva; Ledin, Anna

    2011-01-01

    Urban water managers need to estimate the potential removal of organic micropollutants (MP) in stormwater treatment systems to support MP pollution control strategies. This study documents how the potential removal of organic MP in stormwater treatment systems can be quantified by using multimedia...... models. The fate of four different MP in a stormwater retention pond was simulated by applying two steady-state multimedia fate models (EPI Suite and SimpleBox) commonly applied in chemical risk assessment and a dynamic multimedia fate model (Stormwater Treatment Unit Model for Micro Pollutants — STUMP...... substance inherent properties to calculate MP fate but differ in their ability to represent the small physical scale and high temporal variability of stormwater treatment systems. Therefore the three models generate different results. A Global Sensitivity Analysis (GSA) highlighted that settling...

  5. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery

    Science.gov (United States)

    Singh, Vimal K.; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques

  6. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  7. "It's worth our time": a model of culturally and linguistically supportive professional development for K-12 STEM educators

    Science.gov (United States)

    Charity Hudley, Anne H.; Mallinson, Christine

    2017-09-01

    Professional development on issues of language and culture is often separate from professional development on issues related to STEM education, resulting in linguistic and cultural gaps in K-12 STEM pedagogy and practice. To address this issue, we have designed a model of professional development in which we work with educators to build cultural and linguistic competence and to disseminate information about how educators view the relevance of language, communication, and culture to STEM teaching and learning. We describe the design and facilitation of our model of culturally and linguistically responsive professional development, grounded in theories of multicultural education and culturally supportive teaching, through professional development workshops to 60 K-12 STEM educators from schools in Maryland and Virginia that serve African American students. Participants noted that culturally and linguistically responsive approaches had yet to permeate their K-12 STEM settings, which they identified as a critical challenge to effectively teaching and engaging African-American students. Based on pre-surveys, workshops were tailored to participants' stated needs for information on literacy (e.g., disciplinary literacies and discipline-specific jargon), cultural conflict and mismatch (e.g., student-teacher miscommunication), and linguistic bias in student assessment (e.g., test design). Educators shared feedback via post-workshop surveys, and a subset of 28 participants completed in-depth interviews and a focus group. Results indicate the need for further implementation of professional development such as ours that address linguistic and cultural issues, tailored for K-12 STEM educators. Although participants in this study enumerated several challenges to meeting this need, they also identified opportunities for collaborative solutions that draw upon teacher expertise and are integrated with curricula across content areas.

  8. Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry.

    Science.gov (United States)

    Lee, Si Yeon; Lee, Sangmin; Lee, Jangwook; Yhee, Ji Young; Yoon, Hwa In; Park, Soon-Jung; Koo, Heebeom; Moon, Sung-Hwan; Lee, Hyukjin; Cho, Yong Woo; Kang, Sun Woong; Lee, Sang-Yup; Kim, Kwangmeyung

    2016-10-28

    Labeling of stem cells aims to distinguish transplanted cells from host cells, understand in vivo fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the in vivo evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N-azidoacetyl-d-mannosamine (Ac 4 ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track in vivo fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2017-01-01

    Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

  10. Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering.

    Science.gov (United States)

    Lowenthal, Justin; Gerecht, Sharon

    2016-05-06

    Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine - including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering - have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. In vitro and in vivo differentiation of human embryonic stem cells into retina-like organs and comparison with that from mouse pluripotent epiblast stem cells.

    Science.gov (United States)

    Aoki, Hitomi; Hara, Akira; Niwa, Masayuki; Yamada, Yasuhiro; Kunisada, Takahiro

    2009-09-01

    Correctly inducing the differentiation of pluripotent hESCs to a specific lineage with high purity is highly desirable for regenerative cell therapy. Our first effort to perform in vitro differentiation of hESCs resulted in a limited recapitulation of the ocular tissue structures. When undifferentiated hESCs were placed in vivo into the ocular tissue, in this case into the vitreous cavity, 3-dimensional retina-like structures reminiscent of the invagination of the optic vesicle were generated. Immunohistochemical analysis confirmed the presence of both a neural retina-like cell layer and a retinal pigmented epithelium-like cell layer, possibly equivalent to the developing E12.5 mouse retina. Furthermore, mouse epiblast-derived stem cells, which are reported to share some characteristics with hESCs, but not with mouse ESCs, also generated retinal anlage-like structures in vivo. hESC-derived retina-like structures present a novel therapeutic possibility for retinal diseases and also provide a novel experimental system to study early human eye development. 2009 Wiley-Liss, Inc.

  12. Bidirectional interconversion of stem and non-stem cancer cell populations: A reassessment of theoretical models for tumor heterogeneity

    NARCIS (Netherlands)

    van Neerven, Sanne M.; Tieken, Mathijs; Vermeulen, Louis; Bijlsma, Maarten F.

    2016-01-01

    Resolving the origin of intratumor heterogeneity has proven to be one of the central challenges in cancer research during recent years. Two theoretical models explaining the emergence of intratumor heterogeneity have come to dominate cancer biology literature: the clonal evolution model and the

  13. A Bridge to the Stars: A Model High School-to-College Pipeline for Encouraging Positive STEM Identities

    Science.gov (United States)

    McIntosh, Daniel H.; Jennings, Derrick H.

    2018-01-01

    The need to grow and diversify the STEM workforce remains a critical national challenge. Research shows that STEM identity (how one views herself/himself with respect to STEM) is an important factor for success or failure. A Bridge to the Stars (ABttS) offers URM and low-income high-school students a high impact exposure to science through innovative experiential learning with a professional scientist in freshmen astronomy at UMKC, an urban research university. Showing students who traditionally do not self-identify with high-tech careers that they can succeed in a university science course is a promising way to help build positive STEM identities and aspirations during the critical bridge between high school and college. In five years, we have awarded 45 ABttS scholarships; 93% of these 15-17 year-old students have passed the course satisfactorily with an average grade of 80%. Remarkably, the ABttS scholar performance is on par with that of 600 UMKC students enrolled in the same courses over 8 semesters. Long-term tracking of former scholars shows positive attitudes regarding ABttS and persistence in STEM aspirations at promising rates based on small-number statistics. I will describe the implementation of this unique STEM immersion program offering extended and inclusive engagement in astronomy, arguably the most accessible window to science. I will share classroom and near-peer mentoring innovations, and a new third ABttS tier in which previous scholars can enroll in a freshmen science laboratory experience for UMKC credit. This novel course introduces novices to scientific research and Big Data science through authentic hands-on experiences centered on their own exploration of data from McIntosh's actual research. The long-term mission of ABttS is to see urban educational institutions across the U.S. adopt similar pipelines in all STEM disciplines built on the ABttS model. Adopting programs like ABttS for freshmen STEM majors, especially in urban colleges and

  14. Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger's disease and ischemic limb disease animal model.

    Science.gov (United States)

    Kim, Sung-Whan; Han, Hoon; Chae, Gue-Tae; Lee, Sung-Hoon; Bo, Sun; Yoon, Jung-Hee; Lee, Yong-Soon; Lee, Kwang-Soo; Park, Hwon-Kyum; Kang, Kyung-Sun

    2006-06-01

    Buerger's disease, also known as thromboangiitis obliterans, is a nonatherosclerotic, inflammatory, vasoocclusive disease. It is characterized pathologically as a panangiitis of medium and small blood vessels, including both arteries and adjacent veins, especially the distal extremities (the feet and the hands). There is no curative medication or surgery for this disease. In the present study, we transplanted human leukocyte antigen-matched human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) into four men with Buerger's disease who had already received medical treatment and surgical therapies. After the stem cell transplantation, ischemic rest pain suddenly disappeared from their affected extremities. The necrotic skin lesions were healed within 4 weeks. In the follow-up angiography, digital capillaries were increased in number and size. In addition, vascular resistance in the affected extremities, compared with the preoperative examination, was markedly decreased due to improvement of the peripheral circulation. Because an animal model of Buerger's disease is absent and also to understand human results, we transplanted human UCB-derived MSCs to athymic nude mice with hind limb ischemia by femoral artery ligation. Up to 60% of the hind limbs were salvaged in the femoral artery-ligated animals. By in situ hybridization, the human UCB-derived MSCs were detected in the arterial walls of the ischemic hind limb in the treated group. Therefore, it is suggested that human UCB-derived MSC transplantation may be a new and useful therapeutic armament for Buerger's disease and similar ischemic diseases.

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

    Directory of Open Access Journals (Sweden)

    WY Lai

    2013-10-01

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

  16. Human stem cells as a model for cardiac differentiation and disease

    NARCIS (Netherlands)

    Beqqali, A.; van Eldik, W.; Mummery, C.L.; Passier, R.

    2009-01-01

    Studies on identification, derivation and characterization of human stem cells in the last decade have led to high expectations in the field of regenerative medicine. Although it is clear that for successful stem cell-based therapy several obstacles have to be overcome, other opportunities lay ahead

  17. Enacting STEM in Teacher Development: Toward a Coherent Model of Teacher Preparation

    Science.gov (United States)

    Ruggirello, Rachel; Balcerzak, Phyllis

    2013-01-01

    Various iterations of STEM have been in the forefront of national educational reform of science and math teaching over the last two decades. Most recently, STEM is being viewed as the integration of the sciences, math, technology, and engineering to solve authentic problems, rather than an individual collection of related subjects. This approach…

  18. Modeling Successful STEM High Schools in the United States: An Ecology Framework

    Science.gov (United States)

    Erdogan, Niyazi; Stuessy, Carol L.

    2015-01-01

    This study aims to generate a conceptual framework for specialized Science, Technology, Engineering, and Mathematics (STEM) schools. To do so, we focused on literature and found specialized STEM schools have existed for over 100 years and recently expanded nationwide. The current perception for these schools can be described as unique environments…

  19. 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

  20. Untangling the Biology of Genetic Cardiomyopathies with Pluripotent Stem Cell Disease Models

    NARCIS (Netherlands)

    Buikema, Jan W; Wu, Sean M

    PURPOSE OF REVIEW: Recently, the discovery of strategies to reprogram somatic cells into induced pluripotent stem (iPS) cells has led to a major paradigm change in developmental and stem cell biology. The application of iPS cells and their cardiac progeny has opened novel directions to study

  1. Towards model evaluation and identification using Self-Organizing Maps

    Directory of Open Access Journals (Sweden)

    M. Herbst

    2008-04-01

    Full Text Available The reduction of information contained in model time series through the use of aggregating statistical performance measures is very high compared to the amount of information that one would like to draw from it for model identification and calibration purposes. It has been readily shown that this loss imposes important limitations on model identification and -diagnostics and thus constitutes an element of the overall model uncertainty. In this contribution we present an approach using a Self-Organizing Map (SOM to circumvent the identifiability problem induced by the low discriminatory power of aggregating performance measures. Instead, a Self-Organizing Map is used to differentiate the spectrum of model realizations, obtained from Monte-Carlo simulations with a distributed conceptual watershed model, based on the recognition of different patterns in time series. Further, the SOM is used instead of a classical optimization algorithm to identify those model realizations among the Monte-Carlo simulation results that most closely approximate the pattern of the measured discharge time series. The results are analyzed and compared with the manually calibrated model as well as with the results of the Shuffled Complex Evolution algorithm (SCE-UA. In our study the latter slightly outperformed the SOM results. The SOM method, however, yields a set of equivalent model parameterizations and therefore also allows for confining the parameter space to a region that closely represents a measured data set. This particular feature renders the SOM potentially useful for future model identification applications.

  2. Transferable Atomic Multipole Machine Learning Models for Small Organic Molecules.

    Science.gov (United States)

    Bereau, Tristan; Andrienko, Denis; von Lilienfeld, O Anatole

    2015-07-14

    Accurate representation of the molecular electrostatic potential, which is often expanded in distributed multipole moments, is crucial for an efficient evaluation of intermolecular interactions. Here we introduce a machine learning model for multipole coefficients of atom types H, C, O, N, S, F, and Cl in any molecular conformation. The model is trained on quantum-chemical results for atoms in varying chemical environments drawn from thousands of organic molecules. Multipoles in systems with neutral, cationic, and anionic molecular charge states are treated with individual models. The models' predictive accuracy and applicability are illustrated by evaluating intermolecular interaction energies of nearly 1,000 dimers and the cohesive energy of the benzene crystal.

  3. Self-organized Criticality Model for Ocean Internal Waves

    International Nuclear Information System (INIS)

    Wang Gang; Hou Yijun; Lin Min; Qiao Fangli

    2009-01-01

    In this paper, we present a simple spring-block model for ocean internal waves based on the self-organized criticality (SOC). The oscillations of the water blocks in the model display power-law behavior with an exponent of -2 in the frequency domain, which is similar to the current and sea water temperature spectra in the actual ocean and the universal Garrett and Munk deep ocean internal wave model [Geophysical Fluid Dynamics 2 (1972) 225; J. Geophys. Res. 80 (1975) 291]. The influence of the ratio of the driving force to the spring coefficient to SOC behaviors in the model is also discussed. (general)

  4. Developing cell therapy techniques for respiratory disease: intratracheal delivery of genetically engineered stem cells in a murine model of airway injury

    Science.gov (United States)

    Leblond, Anne-Laure; Naud, Patrice; Forest, Virginie; Gourden, Clothilde; Sagan, Christine; Romefort, Bénédicte; Mathieu, Eva; Delorme, Bruno; Collin, Christine; Pagès, Jean-Christophe; Sensebé, Luc; Pitard, Bruno; Lemarchand, Patricia

    2009-01-01

    Over the past decade, interest has increased in the use of exogenous stem cells to optimize lung repair and serve as carriers of a therapeutic gene for genetic airway disease such as cystic fibrosis. We investigated the survival and the engraftment of exogenous stem cells after intratracheal injection, in a murine model of acute epithelial airway injury already used in gene therapy experiments on cystic fibrosis. Embryonic stem cells and mesenchymal stem cells were intratracheally injected 24hr after 2% polidocanol administration, when epithelial airway injury was maximal. Stem cells were transfected with reporter genes immediately prior to administration. Reporter gene expression was analyzed in trachea-lungs and bronchoalveolar lavages using non-fluorescent, quantitative and sensitive methods. ELISA quantitative results showed that 0.4 to 5.5% stem cells survived in the injured airway. Importantly, no stem cells survived in healthy airway or in the epithelial lining fluid. Using X-Gal staining, transduced mesenchymal stem cells were detected in injured trachea and bronchi lumen. When the epithelium was spontaneously regenerated, the in vivo amount of engrafted mesenchymal stem cells from cell line decreased dramatically. No stem cells from primary culture were located within lungs at 7 days. This study demonstrated the feasibility of the intratracheal cell delivery for airway diseases with acute epithelial injury. PMID:19606934

  5. There Is No Simple Model of the Plasma Membrane Organization

    Science.gov (United States)

    Bernardino de la Serna, Jorge; Schütz, Gerhard J.; Eggeling, Christian; Cebecauer, Marek

    2016-01-01

    Ever since technologies enabled the characterization of eukaryotic plasma membranes, heterogeneities in the distributions of its constituents were observed. Over the years this led to the proposal of various models describing the plasma membrane organization such as lipid shells, picket-and-fences, lipid rafts, or protein islands, as addressed in numerous publications and reviews. Instead of emphasizing on one model we in this review give a brief overview over current models and highlight how current experimental work in one or the other way do not support the existence of a single overarching model. Instead, we highlight the vast variety of membrane properties and components, their influences and impacts. We believe that highlighting such controversial discoveries will stimulate unbiased research on plasma membrane organization and functionality, leading to a better understanding of this essential cellular structure. PMID:27747212

  6. Device model investigation of bilayer organic light emitting diodes

    International Nuclear Information System (INIS)

    Crone, B. K.; Davids, P. S.; Campbell, I. H.; Smith, D. L.

    2000-01-01

    Organic materials that have desirable luminescence properties, such as a favorable emission spectrum and high luminescence efficiency, are not necessarily suitable for single layer organic light-emitting diodes (LEDs) because the material may have unequal carrier mobilities or contact limited injection properties. As a result, single layer LEDs made from such organic materials are inefficient. In this article, we present device model calculations of single layer and bilayer organic LED characteristics that demonstrate the improvements in device performance that can occur in bilayer devices. We first consider an organic material where the mobilities of the electrons and holes are significantly different. The role of the bilayer structure in this case is to move the recombination away from the electrode that injects the low mobility carrier. We then consider an organic material with equal electron and hole mobilities but where it is not possible to make a good contact for one carrier type, say electrons. The role of a bilayer structure in this case is to prevent the holes from traversing the device without recombining. In both cases, single layer device limitations can be overcome by employing a two organic layer structure. The results are discussed using the calculated spatial variation of the carrier densities, electric field, and recombination rate density in the structures. (c) 2000 American Institute of Physics

  7. Financial incentives: alternatives to the altruistic model of organ donation.

    Science.gov (United States)

    Siminoff, L A; Leonard, M D

    1999-12-01

    Improvements in transplantation techniques have resulted in a demand for transplantable organs that far outpaces supply. Present efforts to secure organs use an altruistic system designed to appeal to a public that will donate organs because they are needed. Efforts to secure organs under this system have not been as successful as hoped. Many refinements to the altruistic model have been or are currently being proposed, such as "required request," "mandated choice," "routine notification," and "presumed consent." Recent calls for market approaches to organ procurement reflect growing doubts about the efficacy of these refinements. Market approaches generally use a "futures market," with benefits payable either periodically or when or if organs are procured. Lump-sum arrangements could include donations to surviving family or contributions to charities or to funeral costs. Possibilities for a periodic system of payments include reduced premiums for health or life insurance, or a reciprocity system whereby individuals who periodically reaffirm their willingness to donate are given preference if they require a transplant. Market approaches do raise serious ethical issues, including potential exploitation of the poor. Such approaches may also be effectively proscribed by the 1984 National Organ Transplant Act.

  8. Preventive effects of tonsil-derived mesenchymal stem cells on osteoradionecrosis in a rat model.

    Science.gov (United States)

    Park, Hae Sang; Lee, Jihae; Kim, Jin-Woo; Kim, Ha Young; Jung, Soo Yeon; Lee, Sung Min; Park, Chan Hum; Kim, Han Su

    2018-03-01

    The purpose of this study was to investigate the effects of tonsil-derived mesenchymal stem cells (MSCs) on osteoradionecrosis (ORN). We generated a mandibular ORN rat model using a combination of 20-Gy single-dose irradiation and tooth extraction. Study groups were negative control (tooth extraction only), ORN group (irradiation, tooth extraction), Matrigel-1 group (Matrigel; BD Biosciences, San Jose, CA; irradiation, Matrigel application immediately after tooth extraction), tonsil-derived MSC-1 group (irradiation, tonsil-derived MSC application immediately after tooth extraction), Matrigel-4 group (irradiation, Matrigel application 4 weeks after tooth extraction), and tonsil-derived MSC-4 group (irradiation, tonsil-derived MSC application 4 weeks after tooth extraction). Bone mineral density was significantly lower in the ORN group than in the negative control group. The tonsil-derived MSC-1 group showed significantly higher bone mineral density than did the ORN and tonsil-derived MSC-4 groups. A single 20-Gy dose of irradiation combined with tooth extraction successfully generated ORN in the rat model. The tonsil-derived MSCs can be effective for bone regeneration in ORN, particularly when applied immediately after dentoalveolar trauma or surgery. © 2017 Wiley Periodicals, Inc.

  9. Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.

    Science.gov (United States)

    Bai, Lianhua; Lennon, Donald P; Caplan, Arnold I; DeChant, Anne; Hecker, Jordan; Kranso, Janet; Zaremba, Anita; Miller, Robert H

    2012-06-01

    Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.

  10. Induced pluripotent stem cell-based modeling of neurodegenerative diseases: a focus on autophagy.

    Science.gov (United States)

    Jungverdorben, Johannes; Till, Andreas; Brüstle, Oliver

    2017-07-01

    The advent of cell reprogramming has enabled the generation of induced pluripotent stem cells (iPSCs) from patient skin fibroblasts or blood cells and their subsequent differentiation into tissue-specific cells, including neurons and glia. This approach can be used to recapitulate disease-specific phenotypes in classical cell culture paradigms and thus represents an invaluable asset for disease modeling and drug validation in the framework of personalized medicine. The autophagy pathway is a ubiquitous eukaryotic degradation and recycling system, which relies on lysosomal degradation of unwanted and potentially cytotoxic components. The relevance of autophagy in the pathogenesis of neurodegenerative diseases is underlined by the observation that disease-linked genetic variants of susceptibility factors frequently result in dysregulation of autophagic-lysosomal pathways. In particular, disrupted autophagy is implied in the accumulation of potentially neurotoxic products such as protein aggregates and their precursors and defective turnover of dysfunctional mitochondria. Here, we review the current state of iPSC-based assessment of autophagic dysfunction in the context of neurodegenerative disease modeling. The collected data show that iPSC technology is capable to reveal even subtle alterations in subcellular homeostatic processes, which form the molecular basis for disease manifestation.

  11. Stem Cell-Derived Human Intestinal Organoids as an Infection Model for Rotaviruses

    Science.gov (United States)

    Finkbeiner, Stacy R.; Zeng, Xi-Lei; Utama, Budi; Atmar, Robert L.; Shroyer, Noah F.; Estes, Mary K.

    2012-01-01

    ABSTRACT Directed differentiation of stem cell lines into intestine-like tissue called induced human intestinal organoids (iHIOs) is now possible (J. R. Spence, C. N. Mayhew, S. A. Rankin, M. F. Kuhar, J. E. Vallance, K. Tolle, E. E. Hoskins, V. V. Kalinichenko, S. I. Wells, A. M. Zorn, N. F. Shroyer, and J. M. Wells, Nature 470:105-109, 2011). We tested iHIOs as a new model to cultivate and study fecal viruses. Protocols for infection of iHIOs with a laboratory strain of rotavirus, simian SA11, were developed. Proof-of-principle analyses showed that iHIOs support replication of a gastrointestinal virus, rotavirus, on the basis of detection of nonstructural viral proteins (nonstructural protein 4 [NSP4] and NSP2) by immunofluorescence, increased levels of viral RNA by quantitative reverse transcription-PCR (qRT-PCR), and production of infectious progeny virus. iHIOs were also shown to support replication of 12/13 clinical rotavirus isolates directly from stool samples. An unexpected finding was the detection of rotavirus infection not only in the epithelial cells but also in the mesenchymal cell population of the iHIOs. This work demonstrates that iHIOs offer a promising new model to study rotaviruses and other gastrointestinal viruses. PMID:22761392

  12. Modeling Developmental and Tumorigenic Aspects of Trilateral Retinoblastoma via Human Embryonic Stem Cells.

    Science.gov (United States)

    Avior, Yishai; Lezmi, Elyad; Yanuka, Dorit; Benvenisty, Nissim

    2017-05-09

    Human embryonic stem cells (hESCs) provide a platform for studying human development and understanding mechanisms underlying diseases. Retinoblastoma-1 (RB1) is a key regulator of cell cycling, of which biallelic inactivation initiates retinoblastoma, the most common congenital intraocular malignancy. We developed a model to study the role of RB1 in early development and tumor formation by generating RB1-null hESCs using CRISPR/Cas9. RB1 -/- hESCs initiated extremely large teratomas, with neural expansions similar to those of trilateral retinoblastoma tumors, in which retinoblastoma is accompanied by intracranial neural tumors. Teratoma analysis further revealed a role for the transcription factor ZEB1 in RB1-mediated ectoderm differentiation. Furthermore, RB1 -/- cells displayed mitochondrial dysfunction similar to poorly differentiated retinoblastomas. Screening more than 100 chemotherapies revealed an RB1 -/- -specific cell sensitivity to carboplatin, exploiting their mitochondrial dysfunction. Together, our work provides a human pluripotent cell model for retinoblastoma and sheds light on developmental and tumorigenic roles of RB1. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Astrocytes in a dish: Using pluripotent stem cells to model neurodegenerative and neurodevelopmental disorders.

    Science.gov (United States)

    Crompton, Lucy A; Cordero-Llana, Oscar; Caldwell, Maeve A

    2017-07-01

    Neuroscience and Neurobiology have historically been neuron biased, yet up to 40% of the cells in the brain are astrocytes. These cells are heterogeneous and regionally diverse but universally essential for brain homeostasis. Astrocytes regulate synaptic transmission as part of the tripartite synapse, provide metabolic and neurotrophic support, recycle neurotransmitters, modulate blood flow and brain blood barrier permeability and are implicated in the mechanisms of neurodegeneration. Using pluripotent stem cells (PSC), it is now possible to study regionalised human astrocytes in a dish and to model their contribution to neurodevelopmental and neurodegenerative disorders. The evidence challenging the traditional neuron-centric view of degeneration within the CNS is reviewed here, with focus on recent findings and disease phenotypes from human PSC-derived astrocytes. In addition we compare current protocols for the generation of regionalised astrocytes and how these can be further refined by our growing knowledge of neurodevelopment. We conclude by proposing a functional and phenotypical characterisation of PSC-derived astrocytic cultures that is critical for reproducible and robust disease modelling. © 2017 International Society of Neuropathology.

  14. Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

    Directory of Open Access Journals (Sweden)

    Malihe Nakhaeifard

    2016-02-01

    Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

  15. The effect of cutting origin and organic plant growth regulator on the growth of Daun Ungu (Graptophyllum pictum) through stem cutting method

    Science.gov (United States)

    Pratama, S. P.; Yunus, A.; Purwanto, E.; Widyastuti, Y.

    2018-03-01

    Graptophyllum pictum is one of medical plants which has important chemical content to treat diseases. Leaf, bark and flower can be used to facilitate menstruation, treat hemorrhoid, constipation, ulcers, ulcers, swelling, and earache. G. pictum is difficult to propagated by seedling due to the long duration of seed formation, thusvegetative propagation is done by stem cutting. The aims of this study are to obtain optimum combination of cutting origin and organic plant growth regulator in various consentration for the growth of Daun Ungu through stem cutting method. This research was conducted at Research center for Medicinal Plant and Traditional DrugTanjungsari, Tegal Gede, Karanganyar in June to August 2016. Origin of cuttings and organic plant growth regulator were used as treatments factor. A completely randomized design (RAL) is used and data were analyzed by F test (ANOVA) with a confidence level of 95%. Any significant differences among treatment followed with Duncan test at a = 5%. The research indicates that longest root was resulted from the treatment of 0,5 ml/l of organic plant growth regulator. The treatment of 1 ml/l is able to increase the fresh and dry weight of root, treatment of 1,5 ml/l of organic plant growth regulator was able to increase the percentage of growing shoots. Treatment of base part as origin of cuttings increases the length, fresh weight and and dry weight of shoot, increase the number of leaves. Interaction treatment between 1 ml/l consentration of organic plant growth regulator and central part origin of cuttings is capable of increasing the leaf area, whereas treatment without organic plant growth regulator and base part as planting material affects the smallest leaf area.

  16. Ancestral trees for modeling stem cell lineages genetically rather than functionally: understanding mutation accumulation and distinguishing the restrictive cancer stem cell propagation theory and the unrestricted cell propagation theory of human tumorigenesis.

    Science.gov (United States)

    Shibata, Darryl K; Kern, Scott E

    2008-01-01

    Cancer stem cells either could be rare or common in tumors, constituting the major distinction between the two fundamentally opposed theoretical models of tumor progression: A newer and restrictive stem cell propagation model, in which the stem cells are a small and special minority of the tumor cells, and a standard older model, an unrestricted cell proliferation theory, in which many or most tumor cells are capable of indefinite generations of cell division. Stem cells of tumors are difficult to quantitate using functional assays, and the validity of the most common assays is seriously questioned. Nonetheless, stem cells are an essential component of any tumorigenesis model. Alternative approaches to studying tumor stem cells should be explored. Cell populations can be conceived of as having a genealogy, a relationship of cells to their ancestral lineage, from the zygote to the adult cells or neoplasms. Models using ancestral trees thus offer an anatomic and genetic means to "observe" stem cells independent of artificial conditions. Ancestral trees broaden our attention backward along a lineage, to the zygote stage, and thereby add insight into how the mutations of tumors accumulate. It is possible that a large fraction of mutations in a tumor originate from normal, endogenous, replication errors (nearly all being passenger mutations) occurring prior to the emergence of the first transformed cell. Trees can be constructed from experimental measurements - molecular clocks - of real human tissues and tumors. Detailed analysis of single-cell methylation patterns, heritable yet slightly plastic, now can provide this information in the necessary depth. Trees based on observations of molecular clocks may help us to distinguish between competing theories regarding the proliferative properties among cells of actual human tumors, to observe subtle and difficult phenomena such as the extinction of stem lineages, and to address the origins and rates of mutations in various

  17. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.

    Directory of Open Access Journals (Sweden)

    Jan Tønnesen

    Full Text Available Intrastriatal grafts of stem cell-derived dopamine (DA neurons induce behavioral recovery in animal models of Parkinson's disease (PD, but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2 and halorhodopsin (NpHR, respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.

  18. Modeling of the transient mobility in disordered organic semiconductors

    NARCIS (Netherlands)

    Germs, W.C.; Van der Holst, J.M.M.; Van Mensfoort, S.L.M.; Bobbert, P.A.; Coehoorn, R.

    2011-01-01

    In non-steady-state experiments, the electrical response of devicesbased on disordered organic semiconductors often shows a large transient contribution due to relaxation of the out-of-equilibrium charge-carrier distribution. We have developed a model describing this process, based only on the

  19. There Is No Simple Model of the Plasma Membrane Organization

    Czech Academy of Sciences Publication Activity Database

    de la serna, J. B.; Schütz, G.; Eggeling, Ch.; Cebecauer, Marek

    2016-01-01

    Roč. 4, SEP 2016 (2016), 106 ISSN 2296-634X R&D Projects: GA ČR GA15-06989S Institutional support: RVO:61388955 Keywords : plasma membrane * membrane organization models * heterogeneous distribution Subject RIV: CF - Physical ; Theoretical Chemistry

  20. Waste Reduction Model (WARM) Resources for Small Businesses and Organizations

    Science.gov (United States)

    This page provides a brief overview of how EPA’s Waste Reduction Model (WARM) can be used by small businesses and organizations. The page includes a brief summary of uses of WARM for the audience and links to other resources.

  1. Editorial: Plant organ abscission: from models to crops

    Science.gov (United States)

    The shedding of plant organs is a highly coordinated process essential for both vegetative and reproductive development (Addicott, 1982; Sexton and Roberts, 1982; Roberts et al., 2002; Leslie et al., 2007; Roberts and Gonzalez-Carranza, 2007; Estornell et al., 2013). Research with model plants, name...

  2. Modeling growth of specific spoilage organisms in tilapia ...

    African Journals Online (AJOL)

    enoh

    2012-03-29

    Mar 29, 2012 ... Tilapia is an important aquatic fish, but severe spoilage of tilapia is most likely related to the global aquaculture. The spoilage is mostly caused by specific spoilage organisms (SSO). Therefore, it is very important to use microbial models to predict the growth of SSO in tilapia. This study firstly verified.

  3. A model of virtual organization for corporate visibility and ...

    African Journals Online (AJOL)

    This paper considers the existing numerous research in business, Information and Communication Technology (ICT), examines a theoretical framework for value creation in a virtual world. Following a proposed model, a new strategic paradigm is created for corporate value; and virtual organization (VO) apply the use of ...

  4. Modeling growth of specific spoilage organisms in tilapia ...

    African Journals Online (AJOL)

    Tilapia is an important aquatic fish, but severe spoilage of tilapia is most likely related to the global aquaculture. The spoilage is mostly caused by specific spoilage organisms (SSO). Therefore, it is very important to use microbial models to predict the growth of SSO in tilapia. This study firstly verified Pseudomonas and Vibrio ...

  5. Promoting Representational Competence with Molecular Models in Organic Chemistry

    Science.gov (United States)

    Stull, Andrew T.; Gainer, Morgan; Padalkar, Shamin; Hegarty, Mary

    2016-01-01

    Mastering the many different diagrammatic representations of molecules used in organic chemistry is challenging for students. This article summarizes recent research showing that manipulating 3-D molecular models can facilitate the understanding and use of these representations. Results indicate that students are more successful in translating…

  6. Comparison of ultramicrotomy and focused-ion-beam for the preparation of TEM and STEM cross section of organic solar cells

    DEFF Research Database (Denmark)

    Corazza, Michael; Simonsen, Søren Bredmose; Gnaegi, Helmut

    2016-01-01

    The challenge of preparing cross sections of organic photovoltaics (OPV) suitable for transmission electron microscopy (TEM) and scanning TEM (STEM) is addressed. The samples were polymer solar cells fabricated using roll-to-roll (R2R) processing methods on a flexible polyethylene terephthalate...... resolution, enabling further studies of phase separation of P3HT:PCBM by means of energy filtered TEM (EFTEM). The sample prepared by FIB shows good structure preservation, but reduced resolution due to non-optimal thicknesses achieved after treatment. Degradation studies of samples prepared...

  7. [Personalized Ophthalmology - Induced Pluripotent Stem Cells for In Vitro Modelling of Retinal Degenerative Diseases].

    Science.gov (United States)

    Brandl, Caroline; Weber, Bernhard H F

    2018-02-16

    Today, the search for therapeutic options to treat retinal degeneration often relies on an in-depth understanding of the underlying pathological events. Alternatively, it is conceivable to search, in an undirected screening approach, for chemical compounds affecting disease outcome. For both approaches, there is an urgent need for in vitro and, ideally, in vivo disease models that adequately reflect the site of pathology. Currently available animal models possess limitations as they often develop only defined aspects of disease. Primary cell cultures, derived from the posterior pole of the eye, can only be obtained after invasive surgery or are available post mortem, but due to rapid cell senescence are not suited for long-term analysis. Immortalized retinal cell lines, on the other hand, differ in many aspects from native cells. In this situation, a promising alternative could arise from induced pluripotent stem cells (iPSCs). This cell species can be generated via non-invasive techniques, they are patient-specific, can be propagated indefinitely, and theoretically can be differentiated in all types of retinal cells due to their pluripotent capacities. Importantly, the iPSC-derived retinal cells greatly resemble native cells in many characteristic traits. In this review we present a selection of established in vivo und in vitro models for retinal degenerative disease. We also discuss the potential of iPSCs for personalized in vitro modelling and provide an overview of existent iPSC-derived cell types of the posterior pole, particularly for cells of the retinal pigment epithelium. We finally give an outlook for the potential of such cells for basic research in ophthalmology. Georg Thieme Verlag KG Stuttgart · New York.

  8. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Maaike eHoekstra

    2012-08-01

    Full Text Available Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially characterized.Human iPSC (hiPSC models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these

  9. Modeling Neurodegenerative Microenvironment Using Cortical Organoids Derived from Human Stem Cells.

    Science.gov (United States)

    Yan, Yuanwei; Song, Liqing; Bejoy, Julie; Zhao, Jing; Kanekiyo, Takahisa; Bu, Guojun; Zhou, Yi; Li, Yan

    2018-02-27

    Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and causes cognitive impairment and memory deficits of the patients. The mechanism of AD is not well known, due to lack of human brain models. Recently, mini-brain tissues called organoids have been derived from human induced pluripotent stem cells (hiPSCs) for modeling human brain development and neurological diseases. Thus, the objective of this research is to model and characterize neural degeneration microenvironment using three-dimensional (3D) forebrain cortical organoids derived from hiPSCs and study the response to the drug treatment. It is hypothesized that the 3D forebrain organoids derived from hiPSCs with AD-associated genetic background may partially recapitulate the extracellular microenvironment in neural degeneration. To test this hypothesis, AD-patient derived hiPSCs with presenilin-1 mutation were used for cortical organoid generation. AD-related inflammatory responses, matrix remodeling and the responses to DAPT, heparin (completes with heparan sulfate proteoglycans [HSPGs] to bind Aβ42), and heparinase (digests HSPGs) treatments were investigated. The results indicate that the cortical organoids derived from AD-associated hiPSCs exhibit a high level of Aβ42 comparing with healthy control. In addition, the AD-derived organoids result in an elevated gene expression of proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, upregulate syndecan-3, and alter matrix remodeling protein expression. Our study demonstrates the capacity of hiPSC-derived organoids for modeling the changes of extracellular microenvironment and provides a potential approach for AD-related drug screening.

  10. Modeling secondary organic aerosol formation through cloud processing of organic compounds

    Directory of Open Access Journals (Sweden)

    J. Chen

    2007-10-01

    Full Text Available Interest in the potential formation of secondary organic aerosol (SOA through reactions of organic compounds in condensed aqueous phases is growing. In this study, the potential formation of SOA from irreversible aqueous-phase reactions of organic species in clouds was investigated. A new proposed aqueous-phase chemistry mechanism (AqChem is coupled with the existing gas-phase Caltech Atmospheric Chemistry Mechanism (CACM and the Model to Predict the Multiphase Partitioning of Organics (MPMPO that simulate SOA formation. AqChem treats irreversible organic reactions that lead mainly to the formation of carboxylic acids, which are usually less volatile than the corresponding aldehydic compounds. Zero-dimensional model simulations were performed for tropospheric conditions with clouds present for three consecutive hours per day. Zero-dimensional model simulations show that 48-h average SOA formation is increased by 27% for a rural scenario with strong monoterpene emissions and 7% for an urban scenario with strong emissions of aromatic compounds, respectively, when irreversible organic reactions in clouds are considered. AqChem was also incorporated into the Community Multiscale Air Quality Model (CMAQ version 4.4 with CACM/MPMPO and applied to a previously studied photochemical episode (3–4 August 2004 focusing on the eastern United States. The CMAQ study indicates that the maximum contribution of SOA formation from irreversible reactions of organics in clouds is 0.28 μg m−3 for 24-h average concentrations and 0.60 μg m−3 for one-hour average concentrations at certain locations. On average, domain-wide surface SOA predictions for the episode are increased by 9% when irreversible, in-cloud processing of organics is considered. Because aldehydes of carbon number greater than four are assumed to convert fully to the corresponding carboxylic acids upon reaction with OH in cloud droplets and this assumption may overestimate

  11. Cancer-Specific Inhibitory Effects of Genetically Engineered Stem Cells Expressing Cytosine Deaminase and Interferon-β Against Choriocarcinoma in Xenografted Metastatic Mouse Models

    Directory of Open Access Journals (Sweden)

    Gyu-Sik Kim

    2018-02-01

    Full Text Available Cancer treatments using stem cells expressing therapeutic genes have been identified for various types of cancers. In this study, we investigated inhibitory effects of HB1.F3.CD and HB1.F3.CD.IFN-β cells expressing Escherichia coli cytosine deaminase (CD and human interferon-β (IFN-β genes in intravenously (i.v. injected mice with a metastasis model. In this treatment, pro-drug 5-fluorocytosine (5-FC is converted to cytotoxic drug 5-fluorouracil by hNSCs expressing the CD gene, which inhibits DNA synthesis in cancer cells. Moreover, IFN-β induces apoptosis and reduces the growth of cancer cells. Upon MTT assay, proliferation of choriocarcinoma (JEG-3 cells decreased when co-cultured with hNSCs expressing CD and IFN-β genes. To confirm the cancer-tropic effect of these stem cells, chemoattractant factors (VEGF, CXCR4, and C-kit secreted from JEG-3 cells were identified by polymerase chain reaction. hNSCs migrate toward JEG-3 cells due to ligand-receptor interactions of these factors. Accordingly, the migration capability of hNSCs toward JEG-3 cells was confirmed using an in vitro Trans-well assay, in vivo subcutaneously (s.c. injected mice groups (xenograft model, and metastasis model. Intravenously injected hNSCs migrated freely to other organs when compared to s.c. injected hNSCs. Thus, we confirmed the inhibition of lung and ovarian metastasis of choriocarcinoma by i.v. injected HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. Treatment of these stem cells also increased the survival rates of mice. In conclusion, this study showed that metastatic cancer was diminished by genetically engineered hNSCs and noncytotoxic drug 5-FC. This is the first report of the therapeutic potential of i.v. injected hNSCs in a metastasis model; therefore, the results indicate that this stem cell therapy can be used as an alternative novel tool to treat metastatic choriocarcinoma.

  12. Modeling of secondary organic aerosol yields from laboratory chamber data

    Directory of Open Access Journals (Sweden)

    M. N. Chan

    2009-08-01

    Full Text Available Laboratory chamber data serve as the basis for constraining models of secondary organic aerosol (SOA formation. Current models fall into three categories: empirical two-product (Odum, product-specific, and volatility basis set. The product-specific and volatility basis set models are applied here to represent laboratory data on the ozonolysis of α-pinene under dry, dark, and low-NOx conditions in the presence of ammonium sulfate seed aerosol. Using five major identified products, the model is fit to the chamber data. From the optimal fitting, SOA oxygen-to-carbon (O/C and hydrogen-to-carbon (H/C ratios are modeled. The discrepancy between measured H/C ratios and those based on the oxidation products used in the model fitting suggests the potential importance of particle-phase reactions. Data fitting is also carried out using the volatility basis set, wherein oxidation products are parsed into volatility bins. The product-specific model is most likely hindered by lack of explicit inclusion of particle-phase accretion compounds. While prospects for identification of the majority of SOA products for major volatile organic compounds (VOCs classes remain promising, for the near future empirical product or volatility basis set models remain the approaches of choice.

  13. Development of model for analysing respective collections of intended hematopoietic stem cells and harvests of unintended mature cells in apheresis for autologous hematopoietic stem cell collection.

    Science.gov (United States)

    Hequet, O; Le, Q H; Rodriguez, J; Dubost, P; Revesz, D; Clerc, A; Rigal, D; Salles, G; Coiffier, B

    2014-04-01

    Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (pcells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (pHSC collections and mature unintended cells harvests (pHSC collections or unintended mature cell harvests were pre-leukapheresis blood cell levels. Our model was meant to assist apheresis teams in analysing shares of HSC collected and mature cells harvested with new devices or with new types of HSC mobilization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. On the influence of the exposure model on organ doses

    International Nuclear Information System (INIS)

    Drexler, G.; Eckerl, H.

    1988-01-01

    Based on the design characteristics of the MIRD-V phantom, two sex-specific adult phantoms, ADAM and EVA were introduced especially for the calculation of organ doses resulting from external irradiation. Although the body characteristics of all the phantoms are in good agreement with those of the reference man and woman, they have some disadvantages related to the location and shape of organs and the form of the whole body. To overcome these disadvantages related to the location and shape of organs and form of the whole body. To overcome these disadvantages related to the location and shape of organs and the form of the whole body. To overcome these disadvantages and to obtain more realistic phantoms, a technique based on computer tomographic data (voxel-phantom) was developed. This technique allows any physical phantom or real body to be converted into computer files. The improvements are of special importance with regard to the skeleton, because a better modeling of the bone surfaces and separation of hard bone and bone marrow can be achieved. For photon irradiation, the sensitivity of the model on organ doses or the effective dose equivalent is important for operational radiation protection

  15. Sustainable Organic Farming For Environmental Health A Social Development Model

    Directory of Open Access Journals (Sweden)

    Ijun Rijwan Susanto

    2015-05-01

    Full Text Available ABSTRACT In this study the researcher attempted 1 to understand the basic features of organic farming in The Paguyuban Pasundans Cianjur 2 to describe and understand how the stakeholders were are able to internalize the challenges of organic farming on their lived experiences in the community 3 to describe and understand how the stakeholders were are able to internalize and applied the values of benefits of organic farming in support of environmental health on their lived experiences in the community 4 The purpose was to describe and understand how the stakeholders who are able to articulate their ideas regarding the model of sustainable organic farming 5 The Policy Recommendation for Organic Farming. The researcher employed triangulation thorough finding that provides breadth and depth to an investigation offering researchers a more accurate picture of the phenomenon. In the implementation of triangulation researchers conducted several interviews to get saturation. After completion of the interview results are written compiled and shown to the participants to check every statement by every participant. In addition researchers also checked the relevant documents and direct observation in the field The participants of this study were the stakeholders namely 1 The leader of Paguyuban Pasundans Organic Farmer Cianjur PPOFC 2 Members of Paguyuban Pasundans Organic FarmersCianjur 3 Leader of NGO 4 Government officials of agriculture 5 Business of organic food 6 and Consumer of organic food. Generally the findings of the study revealed the following 1 PPOFC began to see the reality as the impact of modern agriculture showed in fertility problems due to contaminated soil by residues of agricultural chemicals such as chemical fertilizers and chemical pesticides. So he wants to restore the soil fertility through environmentally friendly of farming practices 2 the challenges of organic farming on their lived experiences in the community farmers did not

  16. Study of bone remodeling of two models of femoral cementless stems by means of DEXA and finite elements

    Directory of Open Access Journals (Sweden)

    López-Prats Fernando

    2010-05-01

    Full Text Available Abstract Background A hip replacement with a cemented or cementless femoral stem produces an effect on the bone called adaptive remodelling, attributable to mechanical and biological factors. All of the cementless prostheses designs try to achieve an optimal load transfer in order to avoid stress-shielding, which produces an osteopenia. Long-term densitometric studies taken after implanting ABG-I and ABG-II stems confirm that the changes made to the design and alloy of the ABG-II stem help produce less proximal atrophy of the femur. The simulation with FE allowed us to study the biomechanical behaviour of two stems. The aim of this study was, if possible, to correlate the biological and mechanical findings. Methods Both models with prostheses ABG-I and II have been simulated in five different moments of time which coincide with the DEXA measurements: postoperative, 6 months, 1, 3 and 5 years, in addition to the healthy femur as the initial reference. For the complete comparative analysis of both stems, all of the possible combinations of bone mass (group I and group II of pacients in two controlled studies for ABG-I and II stems, respectively, prosthetic geometry (ABG-I and ABG-II and stem material (Wrought Titanium or TMZF were simulated. Results and Discussion In both groups of bone mass an increase of stress in the area of the cancellous bone is produced, which coincides with the end of the HA coating, as a consequence of the bottleneck effect which is produced in the transmission of loads, and corresponds to Gruen zones 2 and 6, where no osteopenia can be seen in contrast to zones 1 and 7. Conclusions In this study it is shown that the ABG-II stem is more effective than the ABG-I given that it generates higher tensional values on the bone, due to which proximal bone atrophy diminishes. This biomechanical behaviour with an improved transmission of loads confirmed by means of FE simulation corresponds to the biological findings obtained with

  17. Branching and self-organization in marine modular colonial organisms: a model.

    Science.gov (United States)

    Sánchez, Juan Armando; Lasker, Howard R; Nepomuceno, Erivelton G; Sánchez, J Dario; Woldenberg, Michael J

    2004-03-01

    Despite the universality of branching patterns in marine modular colonial organisms, there is neither a clear explanation about the growth of their branching forms nor an understanding of how these organisms conserve their shape during development. This study develops a model of branching and colony growth using parameters and variables related to actual modular structures (e.g., branches) in Caribbean gorgonian corals (Cnidaria). Gorgonians exhibiting treelike networks branch subapically, creating hierarchical mother-daughter relationships among branches. We modeled both the intrinsic subapical branching along with an ecological-physiological limit to growth or maximum number of mother branches (k). Shape is preserved by maintaining a constant ratio (c) between the total number of branches and the mother branches. The size frequency distribution of mother branches follows a scaling power law suggesting self-organized criticality. Differences in branching among species with the same k values are determined by r (branching rate) and c. Species with rr/2 or c>r>0). Ecological/physiological constraints limit growth without altering colony form or the interaction between r and c. The model described the branching dynamics giving the form to colonies and how colony growth declines over time without altering the branching pattern. This model provides a theoretical basis to study branching as a simple function of the number of branches independently of ordering- and bifurcation-based schemes.

  18. Finite-element model of the active organ of Corti

    Science.gov (United States)

    Elliott, Stephen J.; Baumgart, Johannes

    2016-01-01

    The cochlear amplifier that provides our hearing with its extraordinary sensitivity and selectivity is thought to be the result of an active biomechanical process within the sensory auditory organ, the organ of Corti. Although imaging techniques are developing rapidly, it is not currently possible, in a fully active cochlea, to obtain detailed measurements of the motion of individual elements within a cross section of the organ of Corti. This motion is predicted using a two-dimensional finite-element model. The various solid components are modelled using elastic elements, the outer hair cells (OHCs) as piezoelectric elements and the perilymph and endolymph as viscous and nearly incompressible fluid elements. The model is validated by comparison with existing measurements of the motions within the passive organ of Corti, calculated when it is driven either acoustically, by the fluid pressure or electrically, by excitation of the OHCs. The transverse basilar membrane (BM) motion and the shearing motion between the tectorial membrane and the reticular lamina are calculated for these two excitation modes. The fully active response of the BM to acoustic excitation is predicted using a linear superposition of the calculated responses and an assumed frequency response for the OHC feedback. PMID:26888950

  19. High Resolution Modelling of the Congo River's Multi-Threaded Main Stem Hydraulics

    Science.gov (United States)

    Carr, A. B.; Trigg, M.; Tshimanga, R.; Neal, J. C.; Borman, D.; Smith, M. W.; Bola, G.; Kabuya, P.; Mushie, C. A.; Tschumbu, C. L.

    2017-12-01

    We present the results of a summer 2017 field campaign by members of the Congo River users Hydraulics and Morphology (CRuHM) project, and a subsequent reach-scale hydraulic modelling study on the Congo's main stem. Sonar bathymetry, ADCP transects, and water surface elevation data have been collected along the Congo's heavily multi-threaded middle reach, which exhibits complex in-channel hydraulic processes that are not well understood. To model the entire basin's hydrodynamics, these in-channel hydraulic processes must be parameterised since it is not computationally feasible to represent them explicitly. Furthermore, recent research suggests that relative to other large global rivers, in-channel flows on the Congo represent a relatively large proportion of total flow through the river-floodplain system. We therefore regard sufficient representation of in-channel hydraulic processes as a Congo River hydrodynamic research priority. To enable explicit representation of in-channel hydraulics, we develop a reach-scale (70 km), high resolution hydraulic model. Simulation of flow through individual channel threads provides new information on flow depths and velocities, and will be used to inform the parameterisation of a broader basin-scale hydrodynamic model. The basin-scale model will ultimately be used to investigate floodplain fluxes, flood wave attenuation, and the impact of future hydrological change scenarios on basin hydrodynamics. This presentation will focus on the methodology we use to develop a reach-scale bathymetric DEM. The bathymetry of only a small proportion of channel threads can realistically be captured, necessitating some estimation of the bathymetry of channels not surveyed. We explore different approaches to this bathymetry estimation, and the extent to which it influences hydraulic model predictions. The CRuHM project is a consortium comprising the Universities of Kinshasa, Rhodes, Dar es Salaam, Bristol, and Leeds, and is funded by Royal

  20. Mesenchymal stem cells in a transgenic mouse model of multiple system atrophy: immunomodulation and neuroprotection.

    Directory of Open Access Journals (Sweden)

    Sylvia Stemberger

    Full Text Available Mesenchymal stem cells (MSC are currently strong candidates for cell-based therapies. They are well known for their differentiation potential and immunoregulatory properties and have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Currently there is no treatment that provides consistent long-term benefits for patients with multiple system atrophy (MSA, a fatal late onset α-synucleinopathy. Principally neuroprotective or regenerative strategies, including cell-based therapies, represent a powerful approach for treating MSA. In this study we investigated the efficacy of intravenously applied MSCs in terms of behavioural improvement, neuroprotection and modulation of neuroinflammation in the (PLP-αsynuclein (αSYN MSA model.MSCs were intravenously applied in aged (PLP-αSYN transgenic mice. Behavioural analyses, defining fine motor coordination and balance capabilities as well as stride length analysis, were performed to measure behavioural outcome. Neuroprotection was assessed by quantifying TH neurons in the substantia nigra pars compacta (SNc. MSC treatment on neuroinflammation was analysed by cytokine measurements (IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, GM-CSF, INFγ, MCP-1, TGF-β1, TNF-α in brain lysates together with immunohistochemistry for T-cells and microglia. Four weeks post MSC treatment we observed neuroprotection in the SNc, as well as downregulation of cytokines involved in neuroinflammation. However, there was no behavioural improvement after MSC application.To our knowledge this is the first experimental approach of MSC treatment in a transgenic MSA mouse model. Our data suggest that intravenously infused MSCs have a potent effect on immunomodulation and neuroprotection. Our data warrant further studies to elucidate the efficacy of systemically administered MSCs in transgenic MSA models.

  1. Instructional designing the STEM education model for fostering creative thinking abilities in physics laboratory environment classes

    Science.gov (United States)

    Chanthala, Chumpon; Santiboon, Toansakul; Ponkham, Kamon

    2018-01-01

    To investigate the effects of students' activity-based on learning approaching management through the STEM Education Instructional Model for fostering their creative thinking abilities of their learning achievements in physics laboratory classroom environments with the sample size consisted of 48 students at the 10th grade level in two classes in Mahasarakham University Demonstration School(Secondary Division) in Thailand. Students' creative thinking abilities were assessed with the with the 24-item GuilfordCreative Thinking Questionnaire (GCTQ). Students' perceptions of their physics classroom learning environments were obtained using the 35-item Physics Laboratory Environment Inventory (PLEI). Associations between students' learning achievements of their post-test assessment indicated that 26% of the coefficient predictive value (R2) of the variance in students' creative thinking abilities was attributable to their perceptions for the GCTQ. Students' learning outcomes of their post-test assessment, the R2value indicated that 35% of the variances for the PLEI, the R2value indicated that 63% of the variances for their creative thinking abilities were attributable to theiraffecting the activity-based on learning for fostering their creative thinking are provided.

  2. Organizing the space and behavior of semantic models.

    Science.gov (United States)

    Rubin, Timothy N; Kievit-Kylar, Brent; Willits, Jon A; Jones, Michael N

    Semantic models play an important role in cognitive science. These models use statistical learning to model word meanings from co-occurrences in text corpora. A wide variety of semantic models have been proposed, and the literature has typically emphasized situations in which one model outperforms another. However, because these models often vary with respect to multiple sub-processes (e.g., their normalization or dimensionality-reduction methods), it can be difficult to delineate which of these processes are responsible for observed performance differences. Furthermore, the fact that any two models may vary along multiple dimensions makes it difficult to understand where these models fall within the space of possible psychological theories. In this paper, we propose a general framework for organizing the space of semantic models. We then illustrate how this framework can be used to understand model comparisons in terms of individual manipulations along sub-processes. Using several artificial datasets we show how both representational structure and dimensionality-reduction influence a model's ability to pick up on different types of word relationships.

  3. Adipose-Derived Stem Cells Improve Collagenase-Induced Tendinopathy in a Rat Model.

    Science.gov (United States)

    Oshita, Takashi; Tobita, Morikuni; Tajima, Satoshi; Mizuno, Hiroshi

    2016-08-01

    Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment. The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model. The hypothesis was that ASC transplantation would improve degeneration in collagenase-induced tendinopathy. Controlled laboratory study. Sixteen F344/NSlc rats underwent collagenase injection into the Achilles tendon to induce tendinopathy. At 1 week after collagenase injection, 8 rats received ASCs (ASC group) and 8 received phosphate-buffered saline alone (PBS group). Animals were sacrificed at 4 or 12 weeks after ASC administration, and the degree of degeneration in each tendon was histologically evaluated according to the Bonar scale. The microstructure of healing tendons was observed by scanning electron microscopy. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure the ratio of type III collagen messenger RNA (mRNA) to type I collagen mRNA in tendons. The median Bonar scale score in the ASC and PBS groups was 2.5 and 5.33 at 4 weeks after treatment and 1.0 and 4.0 at 12 weeks after treatment, respectively. Histologically, the ASC group showed a significantly lower degree of tendon degeneration than the PBS group at both time points. In the RT-PCR analysis, the ratio of type III collagen to type I collagen was significantly lower in the ASC group than in the PBS group at 12 weeks after treatment. Moreover, this ratio decreased over time in the ASC group, whereas it increased over time in the PBS group. The study findings demonstrate that the application of ASCs results in significant improvement in the

  4. Scaffold composition affects cytoskeleton organization, cell-matrix interaction and the cellular fate of human mesenchymal stem cells upon chondrogenic differentiation.

    Science.gov (United States)

    Li, Yuk Yin; Choy, Tze Hang; Ho, Fu Chak; Chan, Pui Barbara

    2015-06-01

    The stem cell niche, or microenvironment, consists of soluble, matrix, cell and mechanical factors that together determine the cellular fates and/or differentiation patterns of stem cells. Collagen and glycosaminoglycans (GAGs) are important scaffolding materials that can mimic the natural matrix niche. Here, we hypothesize that imposing changes in the scaffold composition or, more specifically, incorporating GAGs into the collagen meshwork, will affect the morphology, cytoskeletal organization and integrin expression profiles, and hence the fate of human mesenchymal stem cells (MSCs) upon the induction of differentiation. Using chondrogenesis as an example, we microencapsulated MSCs in three scaffold systems that had varying matrix compositions: collagen alone (C), aminated collagen (AC) and aminated collagen with GAGs (ACG). We then induced the MSCs to differentiate toward a chondrogenic lineage, after which, we characterized the cell viability and morphology, as well as the level of cytoskeletal organization and the integrin expression profile. We also studied the fate of the MSCs by evaluating the major chondrogenic markers at both the gene and protein level. In C, MSC chondrogenesis was successfully induced and MSCs that spread in the scaffolds had a clear actin cytoskeleton; they expressed integrin α2β1, α5 and αv; promoted sox9 nuclear localization transcription activation; and upregulated the expression of chondrogenic matrix markers. In AC, MSC chondrogenesis was completely inhibited but the scaffold still supported cell survival. The MSCs did not spread and they had no actin cytoskeleton; did not express integrin α2 or αv; they failed to differentiate into chondrogenic lineage cells even on chemical induction; and there was little colocalization or functional interaction between integrin α5 and fibronectin. In ACG, although the MSCs did not express integrin α2, they did express integrin αv and there was strong co-localization and hence functional

  5. Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model.

    Science.gov (United States)

    Schmuck, Eric G; Koch, Jill M; Centanni, John M; Hacker, Timothy A; Braun, Rudolf K; Eldridge, Marlowe; Hei, Derek J; Hematti, Peiman; Raval, Amish N

    2016-12-01

    : Cell tracking is a critical component of the safety and efficacy evaluation of therapeutic cell products. To date, cell-tracking modalities have been hampered by poor resolution, low sensitivity, and inability to track cells beyond the shortterm. Three-dimensional (3D) cryo-imaging coregisters fluorescent and bright-field microcopy images and allows for single-cell quantification within a 3D organ volume. We hypothesized that 3D cryo-imaging could be used to measure cell biodistribution and clearance after intravenous infusion in a rat lung injury model compared with normal rats. A bleomycin lung injury model was established in Sprague-Dawley rats (n = 12). Human mesenchymal stem cells (hMSCs) labeled with QTracker655 were infused via jugular vein. After 2, 4, or 8 days, a second dose of hMSCs labeled with QTracker605 was infused, and animals were euthanized after 60, 120, or 240 minutes. Lungs, liver, spleen, heart, kidney, testis, and intestine were cryopreserved, followed by 3D cryo-imaging of each organ. At 60 minutes, 82% ± 9.7% of cells were detected; detection decreased to 60% ± 17% and 66% ± 22% at 120 and 240 minutes, respectively. At day 2, 0.06% of cells were detected, and this level remained constant at days 4 and 8 postinfusion. At 60, 120, and 240 minutes, 99.7% of detected cells were found in the liver, lungs, and spleen, with cells primarily retained in the liver. This is the first study using 3D cryo-imaging to track hMSCs in a rat lung injury model. hMSCs were retained primarily in the liver, with fewer detected in lungs and spleen. Effective bench-to-bedside clinical translation of cellular therapies requires careful understanding of cell fate through tracking. Tracking cells is important to measure cell retention so that delivery methods and cell dose can be optimized and so that biodistribution and clearance can be defined to better understand potential off-target toxicity and redosing strategies. This article demonstrates, for the first

  6. IT Business Value Model for Information Intensive Organizations

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Gastaud Maçada

    2012-01-01

    Full Text Available Many studies have highlighted the capacity Information Technology (IT has for generating value for organizations. Investments in IT made by organizations have increased each year. Therefore, the purpose of the present study is to analyze the IT Business Value for Information Intensive Organizations (IIO - e.g. banks, insurance companies and securities brokers. The research method consisted of a survey that used and combined the models from Weill and Broadbent (1998 and Gregor, Martin, Fernandez, Stern and Vitale (2006. Data was gathered using an adapted instrument containing 5 dimensions (Strategic, Informational, Transactional, Transformational and Infra-structure with 27 items. The instrument was refined by employing statistical techniques such as Exploratory and Confirmatory Factorial Analysis through Structural Equations (first and second order Model Measurement. The final model is composed of four factors related to IT Business Value: Strategic, Informational, Transactional and Transformational, arranged in 15 items. The dimension Infra-structure was excluded during the model refinement process because it was discovered during interviews that managers were unable to perceive it as a distinct dimension of IT Business Value.

  7. Mobility dependent recombination models for organic solar cells

    Science.gov (United States)

    Wagenpfahl, Alexander

    2017-09-01

    Modern solar cell technologies are driven by the effort to enhance power conversion efficiencies. A main mechanism limiting power conversion efficiencies is charge carrier recombination which is a direct function of the encounter probability of both recombination partners. In inorganic solar cells with rather high charge carrier mobilities, charge carrier recombination is often dominated by energetic states which subsequently trap both recombination partners for recombination. Free charge carriers move fast enough for Coulomb attraction to be irrelevant for the encounter probability. Thus, charge carrier recombination is independent of charge carrier mobilities. In organic semiconductors charge carrier mobilities are much lower. Therefore, electrons and holes have more time react to mutual Coulomb-forces. This results in the strong charge carrier mobility dependencies of the observed charge carrier recombination rates. In 1903 Paul Langevin published a fundamental model to describe the recombination of ions in gas-phase or aqueous solutions, known today as Langevin recombination. During the last decades this model was used to interpret and model recombination in organic semiconductors. However, certain experiments especially with bulk-heterojunction solar cells reveal much lower recombination rates than predicted by Langevin. In search of an explanation, many material and device properties such as morphology and energetic properties have been examined in order to extend the validity of the Langevin model. A key argument for most of these extended models is, that electron and hole must find each other at a mutual spatial location. This encounter may be limited for instance by trapping of charges in trap states, by selective electrodes separating electrons and holes, or simply by the morphology of the involved semiconductors, making it impossible for electrons and holes to recombine at high rates. In this review, we discuss the development of mobility limited

  8. A taxonomy of nursing care organization models in hospitals.

    Science.gov (United States)

    Dubois, Carl-Ardy; D'Amour, Danielle; Tchouaket, Eric; Rivard, Michèle; Clarke, Sean; Blais, Régis

    2012-08-28

    Over the last decades, converging forces in hospital care, including cost-containment policies, rising healthcare demands and nursing shortages, have driven the search for new operational models of nursing care delivery that maximize the use of available nursing resources while ensuring safe, high-quality care. Little is known, however, about the distinctive features of these emergent nursing care models. This article contributes to filling this gap by presenting a theoretically and empirically grounded taxonomy of nursing care organization models in the context of acute care units in Quebec and comparing their distinctive features. This study was based on a survey of 22 medical units in 11 acute care facilities in Quebec. Data collection methods included questionnaire, interviews, focus groups and administrative data census. The analytical procedures consisted of first generating unit profiles based on qualitative and quantitative data collected at the unit level, then applying hierarchical cluster analysis to the units' profile data. The study identified four models of nursing care organization: two professional models that draw mainly on registered nurses as professionals to deliver nursing services and reflect stronger support to nurses' professional practice, and two functional models that draw more significantly on licensed practical nurses (LPNs) and assistive staff (orderlies) to deliver nursing services and are characterized by registered nurses' perceptions that the practice environment is less supportive of their professional work. This study showed that medical units in acute care hospitals exhibit diverse staff mixes, patterns of skill use, work environment design, and support for innovation. The four models reflect not only distinct approaches to dealing with the numerous constraints in the nursing care environment, but also different degrees of approximations to an "ideal" nursing professional practice model described by some leaders in the

  9. Modeling regional secondary organic aerosol using the Master Chemical Mechanism

    Science.gov (United States)

    Li, Jingyi; Cleveland, Meredith; Ziemba, Luke D.; Griffin, Robert J.; Barsanti, Kelley C.; Pankow, James F.; Ying, Qi

    2015-02-01

    A modified near-explicit Master Chemical Mechanism (MCM, version 3.2) with 5727 species and 16,930 reactions and an equilibrium partitioning module was incorporated into the Community Air Quality Model (CMAQ) to predict the regional concentrations of secondary organic aerosol (SOA) from volatile organic compounds (VOCs) in the eastern United States (US). In addition to the semi-volatile SOA from equilibrium partitioning, reactive surface uptake processes were used to simulate SOA formation due to isoprene epoxydiol, glyoxal and methylglyoxal. The CMAQ-MCM-SOA model was applied to simulate SOA formation during a two-week episode from August 28 to September 7, 2006. The southeastern US has the highest SOA, with a maximum episode-averaged concentration of ∼12 μg m-3. Primary organic aerosol (POA) and SOA concentrations predicted by CMAQ-MCM-SOA agree well with AMS-derived hydrocarbon-like organic aerosol (HOA) and oxygenated organic aerosol (OOA) urban concentrations at the Moody Tower at the University of Houston. Predicted molecular properties of SOA (O/C, H/C, N/C and OM/OC ratios) at the site are similar to those reported in other urban areas, and O/C values agree with measured O/C at the same site. Isoprene epoxydiol is predicted to be the largest contributor to total SOA concentration in the southeast US, followed by methylglyoxal and glyoxal. The semi-volatile SOA components are dominated by products from β-caryophyllene oxidation, but the major species and their concentrations are sensitive to errors in saturation vapor pressure estimation. A uniform decrease of saturation vapor pressure by a factor of 100 for all condensable compounds can lead to a 150% increase in total SOA. A sensitivity simulation with UNIFAC-calculated activity coefficients (ignoring phase separation and water molecule partitioning into the organic phase) led to a 10% change in the predicted semi-volatile SOA concentrations.

  10. Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model.

    Directory of Open Access Journals (Sweden)

    Darren Paul Burke

    Full Text Available Extrinsic mechanical signals have been implicated as key regulators of mesenchymal stem cell (MSC differentiation. It has been possible to test different hypotheses for mechano-regulated MSC differentiation by attempting to simulate regenerative events such as bone fracture repair, where repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues such as substrate stiffness and oxygen tension as key regulators of MSC differentiation; however it remains unclear if and how such cues determine stem cell fate in vivo. As part of this study, a computational model was developed to test the hypothesis that substrate stiffness and oxygen tension regulate stem cell differentiation during fracture healing. Rather than assuming mechanical signals act directly on stem cells to determine their differentiation pathway, it is postulated that they act indirectly to regulate angiogenesis and hence partially determine the local oxygen environment within a regenerating tissue. Chondrogenesis of MSCs was hypothesized to occur in low oxygen regions, while in well vascularised regions of the regenerating tissue a soft local substrate was hypothesised to facilitate adipogenesis while a stiff substrate facilitated osteogenesis. Predictions from the model were compared to both experimental data and to predictions of a well established computational mechanobiological model where tissue differentiation is assumed to be regulated directly by the local mechanical environment. The model predicted all the major events of fracture repair, including cartilaginous bridging, endosteal and periosteal bony bridging and bone remodelling. It therefore provides support for the hypothesis that substrate stiffness and oxygen play a key role in regulating MSC fate during regenerative events such as fracture healing.

  11. Prediction model for cabbage stem weevil ceutorhynchus pallidactylus Mrsh. occurrence on winther rape based on an artificial neural network

    Czech Academy of Sciences Publication Activity Database

    Klem, Karel; Spitzer, T.

    2017-01-01

    Roč. 19, č. 3 (2017), s. 302-308 ISSN 1461-9555 R&D Projects: GA MZe QJ1530373 Institutional support: RVO:67179843 Keywords : Brassica napus L * cabbage stem weevil * Ceutorhynchus pallidactylus * model * neural network * oilseed rape * weather conditions Subject RIV: EG - Zoology OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 1.726, year: 2016

  12. MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model.

    Science.gov (United States)

    Ogawa, Yoko; Morikawa, Satoru; Okano, Hideyuki; Mabuchi, Yo; Suzuki, Sadafumi; Yaguchi, Tomonori; Sato, Yukio; Mukai, Shin; Yaguchi, Saori; Inaba, Takaaki; Okamoto, Shinichiro; Kawakami, Yutaka; Tsubota, Kazuo; Matsuzaki, Yumi; Shimmura, Shigeto

    2016-01-26

    Fibrosis of organs is observed in systemic autoimmune disease. Using a scleroderma mouse, we show that transplantation of MHC compatible, minor antigen mismatched bone marrow stromal/stem cells (BMSCs) play a role in the pathogenesis of fibrosis. Removal of donor BMSCs rescued mice from disease. Freshly isolated PDGFRα(+) Sca-1(+) BMSCs expressed MHC class II following transplantation and activated host T cells. A decrease in FOXP3(+) CD25(+) Treg population was observed. T cells proliferated and secreted IL-6 when stimulated with mismatched BMSCs in vitro. Donor T cells were not involved in fibrosis because transplanting T cell-deficient RAG2 knock out mice bone marrow still caused disease. Once initially triggered by mismatched BMSCs, the autoimmune phenotype was not donor BMSC dependent as the phenotype was observed after effector T cells were adoptively transferred into naïve syngeneic mice. Our data suggest that minor antigen mismatched BMSCs trigger systemic fibrosis in this autoimmune scleroderma model.

  13. Lean construction as an effective organization model in Arctic

    Directory of Open Access Journals (Sweden)

    Balashova Elena S.

    2017-01-01

    Full Text Available In recent time, due to the sharp climatic changes, the Arctic attracts an increased interest of the world powers as a strategically important object. In 2013, the development strategy of the Arctic zone of the Russian Federation and national security for the period up to 2020 was approved by the President. In this strategy, the socio-economic development of the region in terms of improving the quality of life, expressed in the implementation of housing and civil engineering is very important. The goal of the study is to identify effective organization model of construction in the Arctic zone of the Russian Federation. Lean construction as a dynamically developing methodology abroad is analyzed. Characteristics of this organization model of construction meet the necessary requirements for the construction of various infrastructure objects in the Arctic. Therefore, the concept of lean construction can be an effective strategy of development of the Arctic regions of Russia as well as other Arctic countries.

  14. Understanding rare disease pathogenesis: a grand challenge for model organisms.

    Science.gov (United States)

    Hieter, Philip; Boycott, Kym M

    2014-10-01

    In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

  15. Drosophila embryos as model to assess cellular and developmental toxicity of multi-walled carbon nanotubes (MWCNT in living organisms.

    Directory of Open Access Journals (Sweden)

    Boyin Liu

    Full Text Available Different toxicity tests for carbon nanotubes (CNT have been developed to assess their impact on human health and on aquatic and terrestrial animal and plant life. We present a new model, the fruit fly Drosophila embryo offering the opportunity for rapid, inexpensive and detailed analysis of CNTs toxicity during embryonic development. We show that injected DiI labelled multi-walled carbon nanotubes (MWCNTs become incorporated into cells in early Drosophila embryos, allowing the study of the consequences of cellular uptake of CNTs on cell communication, tissue and organ formation in living embryos. Fluorescently labelled subcellular structures showed that MWCNTs remained cytoplasmic and were excluded from the nucleus. Analysis of developing ectodermal and neural stem cells in MWCNTs injected embryos revealed normal division patterns and differentiation capacity. However, an increase in cell death of ectodermal but not of neural stem cells was observed, indicating stem cell-specific vulnerability to MWCNT exposure. The ease of CNT embryo injections, the possibility of detailed morphological and genomic analysis and the low costs make Drosophila embryos a system of choice to assess potential developmental and cellular effects of CNTs and test their use in future CNT based new therapies including drug delivery.

  16. Quasi-dynamic model for an organic Rankine cycle

    International Nuclear Information System (INIS)

    Bamgbopa, Musbaudeen O.; Uzgoren, Eray

    2013-01-01

    Highlights: • Study presents a simplified transient modeling approach for an ORC under variable heat input. • The ORC model is presented as a synthesis of its models of its sub-components. • The model is compared to benchmark numerical simulations and experimental data at different stages. - Abstract: When considering solar based thermal energy input to an organic Rankine cycle (ORC), intermittent nature of the heat input does not only adversely affect the power output but also it may prevent ORC to operate under steady state conditions. In order to identify reliability and efficiency of such systems, this paper presents a simplified transient modeling approach for an ORC operating under variable heat input. The approach considers that response of the system to heat input variations is mainly dictated by the evaporator. Consequently, overall system is assembled using dynamic models for the heat exchangers (evaporator and condenser) and static models of the pump and the expander. In addition, pressure drop within heat exchangers is neglected. The model is compared to benchmark numerical and experimental data showing that the underlying assumptions are reasonable for cases where thermal input varies in time. Furthermore, the model is studied on another configuration and mass flow rates of both the working fluid and hot water and hot water’s inlet temperature to the ORC unit are shown to have direct influence on the system’s response

  17. Upregulating CXCR4 in human fetal mesenchymal stem cells enhances engraftment and bone mechanics in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Jones, Gemma N; Moschidou, Dafni; Lay, Kenneth; Abdulrazzak, Hassan; Vanleene, Maximilien; Shefelbine, Sandra J; Polak, Julia; de Coppi, Paolo; Fisk, Nicholas M; Guillot, Pascale V

    2012-01-01

    Stem cells have considerable potential to repair damaged organs and tissues. We previously showed that prenatal transplantation of human first trimester fetal blood mesenchymal stem cells (hfMSCs) in a mouse model of osteogenesis imperfecta (oim mice) led to a phenotypic improvement, with a marked decrease in fracture rate. Donor cells differentiated into mature osteoblasts, producing bone proteins and minerals, including collagen type Iα2, which is absent in nontransplanted mice. This led to modifications of the bone matrix and subsequent decrease of bone brittleness, indicating that grafted cells directly contribute to improvement of bone mechanical properties. Nevertheless, the therapeutic effect was incomplete, attributing to the limited level of engraftment in bone. In this study, we show that although migration of hfMSCs to bone and bone marrow is CXCR4-SDF1 (SDF1 is stromal-derived factor) dependent, only a small number of cells present CXCR4 on the cell surface despite high levels of internal CXCR4. Priming with SDF1, however, upregulates CXCR4 to increase the CXCR4(+) cell fraction, improving chemotaxis in vitro and enhancing engraftment in vivo at least threefold in both oim and wild-type bone and bone marrow. Higher engraftment in oim bones was associated with decreased bone brittleness. This strategy represents a step to improve the therapeutic benefits of fetal cell therapy toward being curative.

  18. Turbulence and Self-Organization Modeling Astrophysical Objects

    CERN Document Server

    Marov, Mikhail Ya

    2013-01-01

    This book focuses on the development of continuum models of natural turbulent media. It provides a theoretical approach to the solutions of different problems related to the formation, structure and evolution of astrophysical and geophysical objects. A stochastic modeling approach is used in the mathematical treatment of these problems, which reflects self-organization processes in open dissipative systems. The authors also consider examples of ordering for various objects in space throughout their evolutionary processes. This volume is aimed at graduate students and researchers in the fields of mechanics, astrophysics, geophysics, planetary and space science.

  19. AGRICULTURAL COOPERATION IN RUSSIA: THE PROBLEM OF ORGANIZATION MODEL CHOICE

    Directory of Open Access Journals (Sweden)

    J. Nilsson

    2008-09-01

    Full Text Available In today's Russia many agricultural co-operatives are established from the top downwards. The national project "Development of Agroindustrial Complex" and other governmental programs initiate the formation of cooperative societies. These cooperatives are organized in accordance with the traditional cooperative model. Many of them do, however, not have any real business activities. The aim of this paper to investigate if traditional cooperatives (following principles such as collective ownership, one member one vote, equal treatment, and solidarity, etc. constitute the best organizational model for cooperatives societies under the present conditions in the Russian agriculture.

  20. Effects of seeding adipose-derived stem cells on electrospun nanocomposite used as chest wall graft in a murine model.

    Science.gov (United States)

    Buschmann, Johanna; Balli, Eleni; Hess, Samuel C; Stark, Wendelin J; Cinelli, Paolo; Märsmann, Sonja; Welti, Manfred; Weder, Walter; Jungraithmayr, Wolfgang

    2017-10-01

    Malignant neoplasms infiltrating the chest wall often requires resection of the thoracic wall. To replace the defect, Gore-Tex ® is usually employed as the gold standard material, however, Gore-Tex ® is inert and not degradable. Novel materials are nowadays available which allow a full bio-integration due to their non-toxic degradability. Additionally, stem cell seeding has the capacity to reduce inflammatory response towards such grafts, thus integrating it better into the host organism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Mapping model behaviour using Self-Organizing Maps

    Directory of Open Access Journals (Sweden)

    M. Herbst

    2009-03-01

    Full Text Available Hydrological model evaluation and identification essentially involves extracting and processing information from model time series. However, the type of information extracted by statistical measures has only very limited meaning because it does not relate to the hydrological context of the data. To overcome this inadequacy we exploit the diagnostic evaluation concept of Signature Indices, in which model performance is measured using theoretically relevant characteristics of system behaviour. In our study, a Self-Organizing Map (SOM is used to process the Signatures extracted from Monte-Carlo simulations generated by the distributed conceptual watershed model NASIM. The SOM creates a hydrologically interpretable mapping of overall model behaviour, which immediately reveals deficits and trade-offs in the ability of the model to represent the different functional behaviours of the watershed. Further, it facilitates interpretation of the hydrological functions of the model parameters and provides preliminary information regarding their sensitivities. Most notably, we use this mapping to identify the set of model realizations (among the Monte-Carlo data that most closely approximate the observed discharge time series in terms of the hydrologically relevant characteristics, and to confine the parameter space accordingly. Our results suggest that Signature Index based SOMs could potentially serve as tools for decision makers inasmuch as model realizations with specific Signature properties can be selected according to the purpose of the model application. Moreover, given that the approach helps to represent and analyze multi-dimensional distributions, it could be used to form the basis of an optimization framework that uses SOMs to characterize the model performance response surface. As such it provides a powerful and useful way to conduct model identification and model uncertainty analyses.

  2. Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

    Full Text Available BACKGROUND: Familial dysautonomia (FD is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion:MU (exon 20 skipping ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation. CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better

  3. Cytomegalovirus pre-emptive therapy after hematopoietic stem cell transplantation in the era of real-time quantitative PCR: comparison with recipients of solid organ transplants.

    Science.gov (United States)

    Panagou, E; Zakout, G; Keshani, J; Smith, C; Irish, D; Mackinnon, S; Kottaridis, P; Fielding, A; Griffiths, P D

    2016-06-01

    Cytomegalovirus (CMV) continues to be an important complication of hematopoietic stem cell transplantation and solid organ transplantation. In this study, 314 patients who underwent hematopoietic stem cell transplantation between January 2003 and October 2011 were tested serially for CMV DNA by real-time quantitative polymerase chain reaction (qPCR) for 90 days post transplantation. Patients with CMV viremia >3000 genomes/mL (equivalent to 2520 IU/mL) received pre-emptive therapy and were compared with previously published data from solid organ transplant (SOT) patients monitored and treated in exactly the same way. After stem cell transplant (SCT), 48% of patients developed at least 1 episode of viremia. The median duration of a viremic episode was 25 days and the peak viral load (VL) was 4784 genomes/mL whole blood (equivalent to 4019 IU/mL). The data demonstrated that recipients with positive CMV serostatus were at increased risk of developing viremia, with 0% of donor-negative/recipient-negative (D-R-), 3.7% of D+R-, 79.5% of D-R+, and 74.2% of D+R+ groups developing viremia over follow-up (adjusted hazard ratio for D+R- vs. D+R+ group 0.03; 95% confidence interval 0.004, 0.18; P = 0.0013). In contrast with SOT patients, where 58/74 (78%) D+R- patients had viremia, a low risk of CMV infection was seen after stem cell transplantation (1/27; 3.7%). As both groups of patients, the previously published SOT patients and the present hematopoietic SCT patients, were monitored using the same protocol and qPCR assay with pre-emptive therapy administered at the same VL cutoffs, the distinct differences seen cannot be explained by differences in testing or management and thus emphasize distinct aspects of the natural history of CMV infection post transplant in these 2 patient groups. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Modelling erosion and its interaction with soil organic carbon.

    Science.gov (United States)

    Oyesiku-Blakemore, Joseph; Verrot, Lucile; Geris, Josie; Zhang, Ganlin; Peng, Xinhua; Hallett, Paul; Smith, Jo

    2017-04-01

    Water driven soil erosion removes and relocates a significant quantity of soil organic carbon. In China the quantity of carbon removed from the soil through water erosion has been reported to be 180+/-80 Mt y-1 (Yue et al., 2011). Being able to effectively model the movement of such a large quantity of carbon is important for the assessment of soil quality and carbon storage in the region and further afield. A large selection of erosion models are available and much work has been done on evaluating the performance of these in developed countries (Merritt et al., 2006). Fewer studies have evaluated the application of these models on soils in developing countries. Here we evaluate and compare the performance of two of these models, WEPP (Laflen et al., 1997) and RUSLE (Renard et al., 1991), for simulations of soil erosion and deposition at the slope scale on a Chinese Red Soil under cultivation using measurements taken at the site. We also describe work to dynamically couple the movement of carbon presented in WEPP to a model of soil organic matter and nutrient turnover, ECOSSE (Smith et al., 2010). This aims to improve simulations of both erosion and carbon cycling by using the simulated rates of erosion to alter the distribution of soil carbon, the depth of soil and the clay content across the slopes, changing the simulated rate of carbon turnover. This, in turn, affects the soil carbon available to be eroded in the next timestep, so improving estimates of carbon erosion. We compare the simulations of this coupled modelling approach with those of the unaltered ECOSSE and WEPP models to determine the importance of coupling erosion and turnover models on the simulation of carbon losses at catchment scale.

  5. Ecotoxicological modelling of cosmetics for aquatic organisms: A QSTR approach.

    Science.gov (United States)

    Khan, K; Roy, K

    2017-07-01

    In this study, externally validated quantitative structure-toxicity relationship (QSTR) models were developed for toxicity of cosmetic ingredients on three different ecotoxicologically relevant organisms, namely Pseudokirchneriella subcapitata, Daphnia magna and Pimephales promelas following the OECD guidelines. The final models were developed by partial least squares (PLS) regression technique, which is more robust than multiple linear regression. The obtained model for P. subcapitata shows that molecular size and complexity have significant impacts on the toxicity of cosmetics. In case of P. promelas and D. magna, we found that the largest contribution to the toxicity was shown by hydrophobicity and van der Waals surface area, respectively. All models were validated using both internal and test compounds employing multiple strategies. For each QSTR model, applicability domain studies were also performed using the "Distance to Model in X-space" method. A comparison was made with the ECOSAR predictions in order to prove the good predictive performances of our developed models. Finally, individual models were applied to predict toxicity for an external set of 596 personal care products having no experimental data for at least one of the endpoints, and the compounds were ranked based on a decreasing order of toxicity using a scaling approach.

  6. An Instructional Development Model for Global Organizations: The GOaL Model.

    Science.gov (United States)

    Hara, Noriko; Schwen, Thomas M.

    1999-01-01

    Presents an instructional development model, GOaL (Global Organization Localization), for use by global organizations. Topics include gaps in language, culture, and needs; decentralized processes; collaborative efforts; predetermined content; multiple perspectives; needs negotiation; learning within context; just-in-time training; and bilingual…

  7. A novel mouse model for non-invasive single marker tracking of mammary stem cells in vivo reveals stem cell dynamics throughout pregnancy.

    Directory of Open Access Journals (Sweden)

    Benjamin J Tiede

    Full Text Available Mammary stem cells (MaSCs play essential roles for the development of the mammary gland and its remodeling during pregnancy. However, the precise localization of MaSCs in the mammary gland and their regulation during pregnancy is unknown. Here we report a transgenic mouse model for luciferase-based single marker detection of MaSCs in vivo that we used to address these issues. Single transgene expressing mammary epithelial cells were shown to reconstitute mammary glands in vivo while immunohistochemical staining identified MaSCs in basal and luminal locations, with preponderance towards the basal position. By quantifying luciferase expression using bioluminescent imaging, we were able to track MaSCs non-invasively in individual mice over time. Using this model to monitor MaSC dynamics throughout pregnancy, we found that MaSCs expand in both total number and percentage during pregnancy and then drop down to or below baseline levels after weaning. However, in a second round of pregnancy, this expansion was not as extensive. These findings validate a powerful system for the analysis of MaSC dynamics in vivo, which will facilitate future characterization of MaSCs during mammary gland development and breast cancer.

  8. Stem cell engineering a WTEC global assessment

    CERN Document Server

    Loring, Jeanne; McDevitt, Todd; Palecek, Sean; Schaffer, David; Zandstra, Peter

    2014-01-01

    This book describes a global assessment of stem cell engineering research, achieved through site visits by a panel of experts to leading institutes, followed by dedicated workshops. The assessment made clear that engineers and the engineering approach with its quantitative, system-based thinking can contribute much to the progress of stem cell research and development. The increased need for complex computational models and new, innovative technologies, such as high-throughput screening techniques, organ-on-a-chip models and in vitro tumor models require an increasing involvement of engineers and physical scientists. Additionally, this book will show that although the US is still in a leadership position in stem cell engineering, Asian countries such as Japan, China and Korea, as well as European countries like the UK, Germany, Sweden and the Netherlands are rapidly expanding their investments in the field. Strategic partnerships between countries could lead to major advances of the field and scalable expansi...

  9. Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Chan, Fong Chun; Mottok, Anja; Gerrie, Alina S; Power, Maryse; Nijland, Marcel; Diepstra, Arjan; van den Berg, Anke; Kamper, Peter; d'Amore, Francesco; d'Amore, Alexander Lindholm; Hamilton-Dutoit, Stephen; Savage, Kerry J; Shah, Sohrab P; Connors, Joseph M; Gascoyne, Randy D; Scott, David W; Steidl, Christian

    2017-11-10

    Purpose Our aim was to capture the biology of classical Hodgkin lymphoma (cHL) at the time of relapse and discover novel and robust biomarkers that predict outcomes after autologous stem-cell transplantation (ASCT). Materials and Methods We performed digital gene expression profiling on a cohort of 245 formalin-fixed, paraffin-embedded tumor specimens from 174 patients with cHL, including 71 with biopsies taken at both primary diagnosis and relapse, to investigate temporal gene expression differences and associations with post-ASCT outcomes. Relapse biopsies from a training cohort of 65 patients were used to build a gene expression-based prognostic model of post-ASCT outcomes (RHL30), and two independent cohorts were used for validation. Results Gene expression profiling revealed that 24% of patients exhibited poorly correlated expression patterns between their biopsies taken at initial diagnosis and relapse, indicating biologic divergence. Comparative analysis of the prognostic power of gene expression measurements in primary versus relapse specimens demonstrated that the biology captured at the time of relapse contained superior properties for post-ASCT outcome prediction. We developed RHL30, using relapse specimens, which identified a subset of high-risk patients with inferior post-ASCT outcomes in two independent external validation cohorts. The prognostic power of RHL30 was independent of reported clinical prognostic markers (both at initial diagnosis and at relapse) and microenvironmental components as assessed by immunohistochemistry. Conclusion We have developed and validated a novel clinically applicable prognostic assay that at the time of first relapse identifies patients with unfavorable post-ASCT outcomes. Moving forward, it will be critical to evaluate the clinical use of RHL30 in the context of positron emission tomography-guided response assessment and the evolving cHL treatment landscape.

  10. Ganglioside-Dependent Neural Stem Cell Proliferation in Alzheimer’s Disease Model Mice

    Directory of Open Access Journals (Sweden)

    Noah A. Koon

    2015-12-01

    Full Text Available The aggregation and formation of amyloid plaques by amyloid β-peptides (Aβs is believed to be one of the pathological hallmarks of Alzheimer’s disease (AD. Intriguingly, Aβs have also been shown to possess proliferative effects on neural stem cells (NSCs. Many essential cellular processes in NSCs, such as fate determination and proliferation, are heavily influenced by cell surface glycoconjugates, including gangliosides. It has recently been shown that Aβ1-42 alters several key glycosyltransferases and glycosidases. To further define the effects of Aβs and to clarify the potential mechanisms of action of those peptides on NSCs, NSCs were cultured from embryonic brains of the double-transgenic mouse model of AD [B6C3-Tg(APPswe,PSEN1dE985Dbo/J] coexpressing mutants of amyloid precursor protein (APPswe and presenilin1 (PSEN1dE9. We found that Aβs not only promoted cell proliferation but also altered expression of several key glycogenes for glycoconjugate metabolism, such as sialyltransferases II and III (ST-II & -III in AD NSCs. In addition, we found upregulation of epidermal growth factor receptor and Notch1 intracellular domain. Moreover, the increased expression of ST-II and -III coincided with the elevated levels of c-series gangliosides (A2B5+ antigens in AD NSCs. Further, we revealed that epidermal growth factor signaling and gangliosides are necessary components on Aβ-stimulated NSC proliferation. Our present study has thus provided a novel mechanism for the upregulation of c-series ganglioside expression and increases in several NSC markers to account for the proliferative effect of Aβs on NSCs in AD mouse brain. These observations support the potential beneficial effects of Aβs and gangliosides in promoting neurogenesis in AD brain.

  11. Ganglioside-Dependent Neural Stem Cell Proliferation in Alzheimer's Disease Model Mice.

    Science.gov (United States)

    Koon, Noah A; Itokazu, Yutaka; Yu, Robert K

    2015-01-01

    The aggregation and formation of amyloid plaques by amyloid β-peptides (Aβs) is believed to be one of the pathological hallmarks of Alzheimer's disease (AD). Intriguingly, Aβs have also been shown to possess proliferative effects on neural stem cells (NSCs). Many essential cellular processes in NSCs, such as fate determination and proliferation, are heavily influenced by cell surface glycoconjugates, including gangliosides. It has recently been shown that Aβ1-42 alters several key glycosyltransferases and glycosidases. To further define the effects of Aβs and to clarify the potential mechanisms of action of those peptides on NSCs, NSCs were cultured from embryonic brains of the double-transgenic mouse model of AD [B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J] coexpressing mutants of amyloid precursor protein (APPswe) and presenilin1 (PSEN1dE9). We found that Aβs not only promoted cell proliferation but also altered expression of several key glycogenes for glycoconjugate metabolism, such as sialyltransferases II and III (ST-II & -III) in AD NSCs. In addition, we found upregulation of epidermal growth factor receptor and Notch1 intracellular domain. Moreover, the increased expression of ST-II and -III coincided with the elevated levels of c-series gangliosides (A2B5+ antigens) in AD NSCs. Further, we revealed that epidermal growth factor signaling and gangliosides are necessary components on Aβ-stimulated NSC proliferation. Our present study has thus provided a novel mechanism for the upregulation of c-series ganglioside expression and increases in several NSC markers to account for the proliferative effect of Aβs on NSCs in AD mouse brain. These observations support the potential beneficial effects of Aβs and gangliosides in promoting neurogenesis in AD brain. © The Author(s) 2015.

  12. Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian [Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J., E-mail: madlamba@oakland.edu [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States)

    2013-12-01

    Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133{sup +} HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b{sup +} counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors.

  13. Induced pluripotent stem cells as a model for telomeric abnormalities in ICF type I syndrome.

    Science.gov (United States)

    Sagie, Shira; Ellran, Erika; Katzir, Hagar; Shaked, Rony; Yehezkel, Shiran; Laevsky, Ilana; Ghanayim, Alaa; Geiger, Dan; Tzukerman, Maty; Selig, Sara

    2014-07-15

    Human telomeric regions are packaged as constitutive heterochromatin, characterized by extensive subtelomeric DNA methylation and specific histone modifications. ICF (immunodeficiency, centromeric instability, facial anomalies) type I patients carry mutations in DNA methyltransferase 3B (DNMT3B) that methylates de novo repetitive sequences during early embryonic development. ICF type I patient fibroblasts display hypomethylated subtelomeres, abnormally short telomeres and premature senescence. In order to study the molecular mechanism by which the failure to de novo methylate subtelomeres results in accelerated telomere shortening, we generated induced pluripotent stem cells (iPSCs) from 3 ICF type I patients. Telomeres were elongated in ICF-iPSCs during reprogramming, and the senescence phenotype was abolished despite sustained subtelomeric hypomethylation and high TERRA levels. Fibroblast-like cells (FLs) isolated from differentiated ICF-iPSCs maintained abnormally high TERRA levels, and telomeres in these cells shortened at an accelerated rate, leading to early senescence, thus recapitulating the telomeric phenotype of the parental fibroblasts. These findings demonstrate that the abnormal telomere phenotype associated with subtelomeric hypomethylation is overridden in cells expressing telomerase, therefore excluding telomerase inhibition by TERRA as a central mechanism responsible for telomere shortening in ICF syndrome. The data in the current study lend support to the use of ICF-iPSCs for modeling of phenotypic and molecular defects in ICF syndrome and for unraveling the mechanism whereby subtelomeric hypomethylation is linked to accelerated telomeric loss in this syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Strontium Hydroxyapatite scaffolds engineered with stem cells aid osteointegration and osteogenesis in osteoporotic sheep model.

    Science.gov (United States)

    Chandran, Sunitha; Shenoy, Sachin J; Babu S, Suresh; P Nair, Renjith; H K, Varma; John, Annie

    2018-03-01

    Osteoporotic fracture healing is an orthopaedic challenge due to excessive bone resorption and impaired osteogenesis. Majority of current treatment strategies focus on regulating bone resorption and the potential application of Mesenchymal Stem Cells (MSCs) in promoting osteogenesis has not been explored much. Furthermore, the present study has put forth a novel approach, wherein the synergistic action of Strontium (Sr) and MSCs in a single implant may facilitate osteoporotic bone healing. Strontium Hydroxyapatite (SrHA) synthesized by wet precipitation was fabricated into tissue engineered Strontium incorporated Hydroxyapatite (cSrHA) using sheep adipose tissue derived MSCs (ADMSCs). Porosity, radiopacity and cytocompatibility of SrHA scaffolds were found appropriate for orthopaedic applications. cSrHA scaffolds exhibited an in vitro Alkaline Phosphatase activity of 20 μmol pnp/30 min comparable to that of Hydroxyapatite (HA) - control scaffold, proving its osteogenic efficacy. Implantation studies in sheep osteoporotic model depicted enhanced osteogenic ability with mature lamellar bone formation in cSrHA implanted group, compared to bare HA, SrHA and tissue engineered HA implanted groups. Histomorphometry data substantiated improved osteogenesis on par with material resorption, as cSrHA implanted group exhibited highest regeneration ratio of 0.38 ± 0.05. Density histograms from micro CT further signified the enhanced osteointegrative ability of cSrHA implants. Results of the study depicted the therapeutic potential of cSrHA in osteoporotic bone healing and proposes the use of allogenic ADMSCs for fabricating "Off the Shelf Tissue Engineered Products". Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Interactive Higher Education Instruction to Advance STEM Instruction in the Environmental Sciences - the Brownfield Action Model

    Science.gov (United States)

    Liddicoat, J. C.; Bower, P.

    2015-12-01

    The U.S. Environmental Protection Agency estimates that presently there are over half a million brownfields in the United States, but this number only includes sites for which an Environmental Site Assessment has been conducted. The actual number of brownfields is certainly in the millions and constitutes one of the major environmental issues confronting all communities today. Taught in part or entirely online for more than 15 years in environmental science, engineering, and hydrology courses at over a dozen colleges, universities, and high schools in the United States, Brownfield Action (BA) is an interactive, web-based simulation that combines scientific expertise, constructivist education philosophy, and multimedia to advance the teaching of environmental science (Bower et al., 2011, 2014; Liddicoat and Bower, 2015). In the online simulation and classroom, students form geotechnical consulting companies with a peer chosen at random to solve a problem in environmental forensics. The BA model contains interdisciplinary scientific and social information that are integrated within a digital learning environment that encourages students to construct their knowledge as they learn by doing. As such, the approach improves the depth and coherence of students understanding of the course material. Like real-world environmental consultants and professionals, students are required to develop and apply expertise from a wide range of fields, including environmental science and engineering as well as journalism, medicine, public health, law, civics, economics, and business management. The overall objective is for students to gain an unprecedented appreciation of the complexity, ambiguity, and risk involved in any environmental issue, and to acquire STEM knowledge that can be used constructively when confronted with such an issue.

  16. [Bone marrow mesenchymal stem cells in Sprague-Dawley rat model of osteoarthritis].

    Science.gov (United States)

    Cui, Y P; Cao, Y P; Liu, H; Yang, X; Meng, Z C; Wang, R

    2015-04-18

    To investigate the efficacy of single time intra-articular different concentration of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) injection in the treatment of Sprague-Dawley (SD) rat model of osteoarthritis (OA). In the study, 32 SD rats were equally randomized into 4 groups: control group, high concentration group (1×10(7)/mL BM-MSCs), low concentration group (5×10(6)/mL BM-MSCs) and high vs. low concentration group. The two knees of each rat were set up to a pair. The induction of OA was performed surgically randomly at one side in model group, and bilaterally in the other groups, which were through anterior cruciate ligament transaction (ACLT) and medial meniscus excising. After the operation, the SD rats were allowed free movement. Four weeks later, different concentrations of allogeneic BM-MSCs isolated from the SD rats, expanded in vitro and suspended in phosphate buffered solution (PBS) were delivered in the articular cavity of both knees; PBS was used as the control. After injection, we excised the femoral nerve and sciatic nerve to disuse the low limb. The cartilage histological sections of knees were scored by Mankin scoring system to assess the severity of the pathology. mRNA of collagen II was detected by real time polymerase chain reaction (RT-PCR). eGFP was detected by fluorescence microscope. Assessments were carried out 4 weeks after the operation in model group, and 3 weeks after injection in the other groups. Mankin scores of the BM-MSCs side and control side were 6.60±0.40 vs. 10.00±0.32 in low concentration group (P0.05). mRNA expression of collagen II of the BM-MSCs side in low concentration group was 106%±1% in contrast to the control side. As in high concentration group it was 108%±1%, and 102%±1% in high vs. low concentration group. Labeled BM-MSCs were detected unexpectedly in the synovial membrane but not in cartilage tissue three weeks from injection. BM-MSCs could promote cartilage repair and inhibit OA progression

  17. Spatiotemporal Organization of Spin-Coated Supported Model Membranes

    Science.gov (United States)

    Simonsen, Adam Cohen

    All cells of living organisms are separated from their surroundings and organized internally by means of flexible lipid membranes. In fact, there is consensus that the minimal requirements for self-replicating life processes include the following three features: (1) information carriers (DNA, RNA), (2) a metabolic system, and (3) encapsulation in a container structure [1]. Therefore, encapsulation can be regarded as an essential part of life itself. In nature, membranes are highly diverse interfacial structures that compartmentalize cells [2]. While prokaryotic cells only have an outer plasma membrane and a less-well-developed internal membrane structure, eukaryotic cells have a number of internal membranes associated with the organelles and the nucleus. Many of these membrane structures, including the plasma membrane, are complex layered systems, but with the basic structure of a lipid bilayer. Biomembranes contain hundreds of different lipid species in addition to embedded or peripherally associated membrane proteins and connections to scaffolds such as the cytoskeleton. In vitro, lipid bilayers are spontaneously self-organized structures formed by a large group of amphiphilic lipid molecules in aqueous suspensions. Bilayer formation is driven by the entropic properties of the hydrogen bond network in water in combination with the amphiphilic nature of the lipids. The molecular shapes of the lipid constituents play a crucial role in bilayer formation, and only lipids with approximately cylindrical shapes are able to form extended bilayers. The bilayer structure of biomembranes was discovered by Gorter and Grendel in 1925 [3] using monolayer studies of lipid extracts from red blood cells. Later, a number of conceptual models were developed to rationalize the organization of lipids and proteins in biological membranes. One of the most celebrated is the fluid-mosaic model by Singer and Nicolson (1972) [4]. According to this model, the lipid bilayer component of

  18. Overexpression of CYP3A4 in a COLO 205 Colon Cancer Stem Cell Model in vitro

    International Nuclear Information System (INIS)

    Olszewski, Ulrike; Liedauer, Richard; Ausch, Christoph; Thalhammer, Theresia; Hamilton, Gerhard

    2011-01-01

    Cancer stem cells (CSCs) seem to constitute a subpopulation of tumor cells that escape from chemotherapy and cause recurrent disease. Low proliferation rates, protection in a stem cell niche and overexpression of drug resistance proteins are considered to confer chemoresistance. We established an in vitro colon CSC-like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium. Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR. ALDH1A1 is a CSC marker for certain tumor entities and confers resistance to cyclophosphamide. CYP3A4 is expressed in liver and colon and its overexpression seems particularly relevant in colon cancer, since it inactivates irinotecan and other xenobiotics, such as taxols and vinca alkaloids. In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients

  19. Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

    Directory of Open Access Journals (Sweden)

    Hong J Lee

    Full Text Available BACKGROUND: Intracerebral hemorrhage (ICH is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

  20. StatSTEM: An efficient approach for accurate and precise model-based quantification of atomic resolution electron microscopy images.

    Science.gov (United States)

    De Backer, A; van den Bos, K H W; Van den Broek, W; Sijbers, J; Van Aert, S

    2016-12-01

    An efficient model-based estimation algorithm is introduced to quantify the atomic column positions and intensities from atomic resolution (scanning) transmission electron microscopy ((S)TEM) images. This algorithm uses the least squares estimator on image segments containing individual columns fully accounting for overlap between neighbouring columns, enabling the analysis of a large field of view. For this algorithm, the accuracy and precision with which measurements for the atomic column positions and scattering cross-sections from annular dark field (ADF) STEM images can be estimated, has been investigated. The highest attainable precision is reached even for low dose images. Furthermore, the advantages of the model-based approach taking into account overlap between neighbouring columns are highlighted. This is done for the estimation of the distance between two neighbouring columns as a function of their distance and for the estimation of the scattering cross-section which is compared to the integrated intensity from a Voronoi cell. To provide end-users this well-established quantification method, a user friendly program, StatSTEM, is developed which is freely available under a GNU public license. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Atorvastatin treatment improves effects of implanted mesenchymal stem cells: meta-analysis of animal models with acute myocardial infarction.

    Science.gov (United States)

    Dai, Guo; Xu, Qing; Luo, Rong; Gao, Jianfang; Chen, Hui; Deng, Yun; Li, Yongqing; Wang, Yuequn; Yuan, Wuzhou; Wu, Xiushan

    2015-12-14

    Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies. Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI. In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P 0.05) and inconsistency (I(2): 22 %). Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.

  2. 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders.

    Science.gov (United States)

    Lee, Chun-Ting; Bendriem, Raphael M; Wu, Wells W; Shen, Rong-Fong

    2017-08-20

    Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer's disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders.

  3. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy.

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    Dhruv Sareen

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC lines generated from two Type I SMA subjects-one produced with lentiviral constructs and the second using a virus-free plasmid-based approach-recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients.

  4. Generation of an ICF Syndrome Model by Efficient Genome Editing of Human Induced Pluripotent Stem Cells Using the CRISPR System

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    Izuho Hatada

    2013-09-01

    Full Text Available Genome manipulation of human induced pluripotent stem (iPS cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells.

  5. Pathophysiological changes of the cerebellum and brain stem in a rabbit model after superior petrosal vein sacrifice.

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    Cheng, Lei; Guo, Pin; Liao, Yi-Wei; Zhang, Hong-Liang; Li, Huan-Ting; Yuan, Xianrui

    2017-11-13

    In certain surgical procedures sacrifice of the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction or hemorrhage might occur after sectioning of the SPV. This study investigated the pathophysiological changes of cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48 and 72 hours groups which represented the time period from sacrifice of the SPV to sacrifice of the rabbits. The water content (WC), Na + content, K + content and pathophysiological changes of cerebellum and brain stem tissue were measured. In comparison to the control, the WC and Na + content of cerebellar tissue were increased in the 4h, 8h, 12h and 24h operation subgroups (psacrifice of the SPV in the rabbit model. ©2017 The Author(s).

  6. OBJECT ORIENTED MODELLING, A MODELLING METHOD OF AN ECONOMIC ORGANIZATION ACTIVITY

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    TĂNĂSESCU ANA

    2014-05-01

    Full Text Available Now, most economic organizations use different information systems types in order to facilitate their activity. There are different methodologies, methods and techniques that can be used to design information systems. In this paper, I propose to present the advantages of using the object oriented modelling at the information system design of an economic organization. Thus, I have modelled the activity of a photo studio, using Visual Paradigm for UML as a modelling tool. For this purpose, I have identified the use cases for the analyzed system and I have presented the use case diagram. I have, also, realized the system static and dynamic modelling, through the most known UML diagrams.

  7. Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

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    Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Cat