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409 results on '"Steindler, Dennis A."'

61. Space Exploration: A Risk for Neural Stem Cells

Author

Encinas, Juan M, Vazquez, Marcelo E, Switzer, Robert C, Chamberland, Dennis W, Nick, Harry, Levine, Howard G, Scarpa, Philip J, Enikolopov, Grigori, and Steindler, Dennis A

Subjects
Aerospace Medicine
Abstract

During spaceflights beyond low Earth orbit, astronauts are exposed to potentially carcinogenic and tissue damaging galactic cosmic rays, solar proton events, and secondary radiation that includes neutrons and recoil nuclei produced by nuclear reactions in spacecraft walls or in tissue (1). Such radiation risk may present a significant health risk for human exploration of the moon and Mars. Emerging evidence that generation of new neurons in the adult brain may be essential for learning, memory, and mood (2) and that radiation is deleterious to neurogenesis (3-5) underscores a previously unappreciated possible risk to the cognitive functions and emotional stability of astronauts exposed to radiation in space. Here we use a novel reporter mouse line to identify at-risk populations of stem and progenitor cells in the brain and find, unexpectedly, that quiescent stem-like cells (rather than their rapidly dividing progeny) in the hippocampus constitute the most vulnerable cell population. This finding raises concerns about the possible risks facing astronauts on long duration space missions.

Published
2006

67. Exosome/microvesicle content is altered in leucine‐rich repeat kinase 2 mutant induced pluripotent stem cell‐derived neural cells.

Author

Candelario, Kate M., Balaj, Leonora, Zheng, Tong, Skog, Johan, Scheffler, Bjorn, Breakefield, Xandra, Schüle, Birgitt, and Steindler, Dennis A.

Abstract

Extracellular vesicles, including exosomes/microvesicles (EMVs), have been described as sensitive biomarkers that represent disease states and response to therapies. In light of recent reports of disease‐mirroring EMV molecular signatures, the present study profiled two EMVs from different Parkinson's disease (PD) tissue sources: (a) neural progenitor cells derived from an endogenous adult stem/progenitor cell, called adult human neural progenitor (AHNP) cells, that we found to be pathological when isolated from postmortem PD patients' substantia nigra; and (b) leucine‐rich repeat kinase 2 (LRRK2) gene identified patient induced pluripotent stem cells (iPSCs), which were used to isolate EMVs and begin to characterize their cargoes. Initial characterization of EMVs derived from idiopathic patients (AHNPs) and mutant LRRK2 patients showed differences between both phenotypes and when compared with a sibling control in EMV size and release based on Nanosight analysis. Furthermore, molecular profiling disclosed that neurodegenerative‐related gene pathways altered in PD can be reversed using gene‐editing approaches. In fact, the EMV cargo genes exhibited normal expression patterns after gene editing. This study shows that EMVs have the potential to serve as sensitive biomarkers of disease state in both idiopathic and gene‐identified PD patients and that following gene‐editing, EMVs reflect a corrected state. This is relevant for both prodromal and symptomatic patient populations where potential responses to therapies can be monitored via non‐invasive liquid biopsies and EMV characterizations. [ABSTRACT FROM AUTHOR]

Published
2020
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68. S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma

Author

Chow, Kin-Hoe, primary, Park, Hee Jung, additional, George, Joshy, additional, Yamamoto, Keiko, additional, Gallup, Andrew D., additional, Graber, Joel H., additional, Chen, Yuanxin, additional, Jiang, Wen, additional, Steindler, Dennis A., additional, Neilson, Eric G., additional, Kim, Betty Y.S., additional, and Yun, Kyuson, additional

Published
2017
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69. Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma

Author

Reinartz, Roman, primary, Wang, Shanshan, additional, Kebir, Sied, additional, Silver, Daniel J., additional, Wieland, Anja, additional, Zheng, Tong, additional, Küpper, Marius, additional, Rauschenbach, Laurèl, additional, Fimmers, Rolf, additional, Shepherd, Timothy M., additional, Trageser, Daniel, additional, Till, Andreas, additional, Schäfer, Niklas, additional, Glas, Martin, additional, Hillmer, Axel M., additional, Cichon, Sven, additional, Smith, Amy A., additional, Pietsch, Torsten, additional, Liu, Ying, additional, Reynolds, Brent A., additional, Yachnis, Anthony, additional, Pincus, David W., additional, Simon, Matthias, additional, Brüstle, Oliver, additional, Steindler, Dennis A., additional, and Scheffler, Björn, additional

Published
2017
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70. Bone marrow transdifferentiation in brain after transplantation: a retrospective study

Author

Cogle, Christopher R., Yachnis, Anthony T., Laywell, Eric D., Zander, Dani S., Wingard, John R., Steindler, Dennis A., and Scott, Edward W.

Subjects
Central nervous system -- Health aspects, Hematopoietic stem cells -- Health aspects, Hematopoietic stem cells -- Research, Graft versus host reaction -- Care and treatment
Published
2004

72. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain

Author

Laywell, Eric D., Rakic, Pasko, Kukekov, Valery G., Holland, Eric C., and Steindler, Dennis A.

Subjects
Astrocytes -- Research, Stem cells -- Research, Brain research -- Analysis, Central nervous system -- Research, Science and technology
Abstract

The mammalian brain contains a population of neural stem cells (NSC) that can both self-renew and generate progeny along the three lineage pathways of the central nervous system (CNS), but the in vivo identification and localization of NSC in the postnatal CNS has proved elusive. Recently, separate studies have implicated ciliated ependymal (CE) cells, and special subependymal zone (SEZ) astrocytes as candidates for NSC in the adult brain. In the present study, we have examined the potential of these two NSC candidates to form multipotent spherical clones--neurospheres--in vitro. We conclude that CE cells are unipotent and give rise only to cells within the gila cell lineage, although they are capable of forming spherical clones when cultured in isolation. In contrast, astrocyte monolayers from the cerebral cortex, cerebellum, spinal cord, and SEZ can form neurospheres that give rise both to neurons and glia. However, the ability to form neurospheres is restricted to astrocyte monolayers derived during the first 2 postnatal wk, except for SEZ astrocytes, which retain this capacity in the mature forebrain. We conclude that environmental factors, simulated by certain in vitro conditions, transiently confer NSC-like attributes on astrocytes during a critical period in CNS development.

Published
2000

75. Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition.

Author

Achoui, Dalila, Siebzehnrübl, Florian A., Steindler, Dennis A., Aigner, Ludwig, Couillard-Despres, Sebastien, Paucar, Martin Arce, Svenningsson, Per, Osmand, Alexander, Andreew, Alexander, Zabel, Claus, Weiss, Andreas, Kuhn, Rainer, Moussaoui, Saliha, Blockx, Ines, Van der Linden, Annemie, Cheong, Rachel Y., Petersén, Åsa, Roybon, Laurent, Gupta, Bhavana, and Raber, Kerstin A.

Subjects
HUNTINGTON disease, HUNTINGTIN protein, NEURODEGENERATION, CHROMOSOME abnormalities, EMBRYONIC stem cell research
Abstract

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT). Although mutant HTT is expressed during embryonic development and throughout life, clinical HD usually manifests later in adulthood. A number of studies document neurodevelopmental changes associated with mutant HTT, but whether these are reversible under therapy remains unclear. Here, we identify very early behavioral, molecular, and cellular changes in preweaning transgenic HD rats and mice. Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. Interventional treatment of this early phenotype with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and markers of dopaminergic neurotransmission and complete reversal of aberrant neuronal differentiation in vitro and in vivo. Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD. [ABSTRACT FROM AUTHOR]

Published
2018
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78. Stem cell therapies as an emerging paradigm in stroke (STEPS)

Author

Wechsler, Lawrence, Steindler, Dennis, Borlongan, Cesar, Chopp, Michael, Savitz, Sean, Deans, Robert, Caplan, Louis, Hess, David, Mays, Robert W., Boltze, Johannes, and Publica

Subjects
Schlaganfall, Zelltherapie, Stammzelle, analeptische Therapie
Abstract

Investigators developing cellular therapy for stroke face many challenges. Preclinical models used for cellular therapy studies should be relevant to human stroke and predictive of benefit despite differences in stroke size, cerebrovascular anatomy, immune status, and neurological responses. Translating preclinical testing to human trials is compounded by consideration of delivery method and translation of dosing with cell survival. Many issues must be approached in designing clinical trials of cellular therapy for stroke, including appropriate outcome measures, controlling for confounding factors such as rehabilitation therapy, and possible surrogate outcomes using imaging such as MRI and newer imaging techniques. It is also important to establish standardized clinical protocols and clinical database registries in advance of early proof-of-concept studies. Investigators must adopt a standardized nomenclature and characterization schema for cell products to accurately define potency and determine clinical outcome from early proof-of-concept studies. The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.

Published
2009

79. Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis1

Author

Gibbs, C. Parker, Kukekov, Valery G., Reith, John D., Tchigrinova, Olga, Suslov, Oleg N., Scott, Edward W., Ghivizzani, Steven C., Ignatova, Tatyana N., and Steindler, Dennis A.

Subjects
Osteosarcoma, Embryonal Carcinoma Stem Cells, Brief Article, Reverse Transcriptase Polymerase Chain Reaction, Cell Culture Techniques, Neoplastic Stem Cells, Humans, Bone Neoplasms, Cell Differentiation, Immunohistochemistry, Cell Division, Culture Media, Serum-Free, DNA Primers
Abstract

Bone sarcomas are a clinically and molecularly heterogeneous group of malignancies characterized by varying degrees of mesenchymal differentiation. Despite advances in medical and surgical management, survival rates for high-grade tumors have remained static at 50% to 70%. Tumor stem cells have been recently implicated in the pathogenesis of other heterogeneous, highly malignant tumors. We demonstrate here the existence of a small subpopulation of self-renewing bone sarcoma cells that are capable of forming suspended spherical, clonal colonies, also called "sarcospheres," in anchorage-independent, serum-starved conditions. These bone sarcoma cells as well as tissue specimens express activated STAT3 and the marker genes of pluripotent embryonic stem (ES) cells, Oct 3/4 and Nanog. Expression levels of Oct 3/4 and Nanog are greater in sarcospheres than in adherent cultures. A subset of bone sarcoma cells displays several surface markers of mesenchymal stem cells (Stro-1, CD105, and CD44) as well as attributes of mesodermal, ectodermal, and endodermal differentiation. Although previously documented in brain and breast tumors, our results support the extension of the cancer stem cell hypothesis to include tumors of mesenchymal lineage. Furthermore, they suggest the participation of ES cell homeobox proteins in non-germ cell tumorigenesis.

Published
2005

85. Increased Precursor Cell Proliferation after Deep Brain Stimulation for Parkinson's Disease: A Human Study

Author

Vedam-Mai, Vinata, primary, Gardner, Bronwen, additional, Okun, Michael S., additional, Siebzehnrubl, Florian A., additional, Kam, Monica, additional, Aponso, Palingu, additional, Steindler, Dennis A., additional, Yachnis, Anthony T., additional, Neal, Dan, additional, Oliver, Brittany U., additional, Rath, Sean J., additional, Faull, Richard L. M., additional, Reynolds, Brent A., additional, and Curtis, Maurice A., additional

Published
2014
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86. Purification of immature neuronal cells from neural stem cell progeny

Author

Azari, Hassan, Osborne, Geoffrey W, Yasuda, Takahiro, Golmohammadi, Mohammad G, Rahman, Maryam, Deleyrolle, Loic P, Esfandiari, Ebrahim, Adams, David J, Scheffler, Bjorn, Steindler, Dennis A, Reynolds, Brent A, Azari, Hassan, Osborne, Geoffrey W, Yasuda, Takahiro, Golmohammadi, Mohammad G, Rahman, Maryam, Deleyrolle, Loic P, Esfandiari, Ebrahim, Adams, David J, Scheffler, Bjorn, Steindler, Dennis A, and Reynolds, Brent A

Abstract

Large-scale proliferation and multi-lineage differentiation capabilities make neural stem cells (NSCs) a promising renewable source of cells for therapeutic applications. However, the practical application for neuronal cell replacement is limited by heterogeneity of NSC progeny, relatively low yield of neurons, predominance of astrocytes, poor survival of donor cells following transplantation and the potential for uncontrolled proliferation of precursor cells. To address these impediments, we have developed a method for the generation of highly enriched immature neurons from murine NSC progeny. Adaptation of the standard differentiation procedure in concert with flow cytometry selection, using scattered light and positive fluorescent light selection based on cell surface antibody binding, provided a near pure (97%) immature neuron population. Using the purified neurons, we screened a panel of growth factors and found that bone morphogenetic protein-4 (BMP-4) demonstrated a strong survival effect on the cells in vitro, and enhanced their functional maturity. This effect was maintained following transplantation into the adult mouse striatum where we observed a 2-fold increase in the survival of the implanted cells and a 3-fold increase in NeuN expression. Additionally, based on the neural-colony forming cell assay (N-CFCA), we noted a 64 fold reduction of the bona fide NSC frequency in neuronal cell population and that implanted donor cells showed no signs of excessive or uncontrolled proliferation. The ability to provide defined neural cell populations from renewable sources such as NSC may find application for cell replacement therapies in the central nervous system.

Published
2011

88. Anticancer Effects of Niclosamide in Human Glioblastoma

Author

Wieland, Anja, primary, Trageser, Daniel, additional, Gogolok, Sabine, additional, Reinartz, Roman, additional, Höfer, Heike, additional, Keller, Mihaela, additional, Leinhaas, Anke, additional, Schelle, Ramona, additional, Normann, Sabine, additional, Klaas, Lil, additional, Waha, Andreas, additional, Koch, Philipp, additional, Fimmers, Rolf, additional, Pietsch, Torsten, additional, Yachnis, Anthony T., additional, Pincus, David W., additional, Steindler, Dennis A., additional, Brüstle, Oliver, additional, Simon, Matthias, additional, Glas, Martin, additional, and Scheffler, Björn, additional

Published
2013
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89. Abstract 4906: ZEB1 maintains self-renewal, invasion and chemoresistance of glioblastoma stem cells.

Author

Siebzehnrubl, Florian A., primary, Silver, Daniel J., additional, Tugertimur, Bugra, additional, Deleyrolle, Loic P., additional, Siebzehnrubl, Dorit, additional, Sarkisian, Matthew R., additional, Devers, Kelly G., additional, Yachnis, Antony T., additional, Kupper, Marius D., additional, Neal, Daniel, additional, Nabilsi, Nancy H., additional, Kladde, Michael P., additional, Suslov, Oleg, additional, Brabletz, Simone, additional, Brabletz, Thomas, additional, Reynolds, Brent A., additional, and Steindler, Dennis A., additional

Published
2013
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90. Abstract 1639: Chondroitin sulfate proteoglycans potently inhibit invasion and serve as a central organizer of the brain tumor microenvironment.

Author

Silver, Daniel J., primary, Siebzehnrubl, Florian A., additional, Schildts, Michela J., additional, Yachnis, Anthony T., additional, Smith, George M., additional, Smith, Amy A., additional, Scheffler, Bjorn, additional, Reynolds, Brent A., additional, Silver, Jerry, additional, and Steindler, Dennis A., additional

Published
2013
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96. Abstract 4308: ZEB1 mediates invasion and chemoresistance of glioblastoma

Author

Siebzehnrubl, Florian, primary, Silver, Daniel, additional, Tugertimur, Bugra, additional, Deleyrolle, Loic, additional, Suslov, Oleg, additional, Siebzehnrubl, Dorit, additional, Sarkisian, Matthew, additional, Kuepper, Marius, additional, Yachnis, Antony, additional, Brabletz, Simone, additional, Brabletz, Thomas, additional, Reynolds, Brent, additional, and Steindler, Dennis, additional

Published
2012
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97. Purification of Immature Neuronal Cells from Neural Stem Cell Progeny

Author

Azari, Hassan, primary, Osborne, Geoffrey W., additional, Yasuda, Takahiro, additional, Golmohammadi, Mohammad G., additional, Rahman, Maryam, additional, Deleyrolle, Loic P., additional, Esfandiari, Ebrahim, additional, Adams, David J., additional, Scheffler, Bjorn, additional, Steindler, Dennis A., additional, and Reynolds, Brent A., additional

Published
2011
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