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Retinal stem cells

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https://www.readbyqxmd.com/read/28428049/stem-cells-for-retinal-disease-a-perspective-on-the-promise-and-perils
#1
Rajesh C Rao, Vaidehi S Dedania, Mark W Johnson
PURPOSE: To summarize key concepts, and early safety and efficacy signals from clinical trials for stem/progenitor cell-based interventions for retinal disease. DESIGN: Interpretive essay. METHODS: Review and synthesis of selected recent reports of stem/progenitor cell-based approaches for retinal disease, with interpretation and perspective. RESULTS: Stem/progenitor cell-based interventions represent a novel class of potential therapies for retinal diseases, such as age-related macular degeneration, inherited retinal dystrophies, and others...
April 17, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28424578/the-crb1-complex-following-the-trail-of-crumbs-to-a-feasible-gene-therapy-strategy
#2
REVIEW
Peter M Quinn, Lucie P Pellissier, Jan Wijnholds
Once considered science fiction, gene therapy is rapidly becoming scientific reality, targeting a growing number of the approximately 250 genes linked to hereditary retinal disorders such as retinitis pigmentosa and Leber's congenital amaurosis. Powerful new technologies have emerged, leading to the development of humanized models for testing and screening these therapies, bringing us closer to the goal of personalized medicine. These tools include the ability to differentiate human induced pluripotent stem cells (iPSCs) to create a "retina-in-a-dish" model and the self-formed ectodermal autonomous multi-zone, which can mimic whole eye development...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28423611/the-stem-cell-cancer-stem-cell-marker-aldh1a3-regulates-the-expression-of-the-survival-factor-tissue-transglutaminase-in-mesenchymal-glioma-stem-cells
#3
Kelly E Sullivan, Kathy Rojas, Richard A Cerione, Ichiro Nakano, Kristin F Wilson
Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and acyltransferase activities, has been implicated in the survival and chemotherapy resistance of aggressive cancer cells and cancer stem cells, including glioma stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs referred to as proneural (PN) and mesenchymal (MES), we find that the phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and survival of these cells was sensitive to treatment with tTG inhibitors, with a benefit being observed when combined with the standard of care for high grade gliomas (i...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416692/immunomodulation-accelerated-neuronal-regeneration-following-selective-rod-photoreceptor-cell-ablation-in-the-zebrafish-retina
#4
David T White, Sumitra Sengupta, Meera T Saxena, Qingguo Xu, Justin Hanes, Ding Ding, Hongkai Ji, Jeff S Mumm
Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415701/wogonin-induces-retinal-neuron-like-differentiation-of-bone-marrow-stem-cells-by-inhibiting-notch-1-signaling
#5
Qinmeng Shu, Hong Zhuang, Jiawen Fan, Xin Wang, Gezhi Xu
Age-related macular degeneration and retinitis pigmentosa are major causes of irreversible vision loss in the elderly and, despite sustained efforts, current treatments are largely ineffective. Wogonin is a bioactive plant flavonoid possessing a range of beneficial properties, including neuroprotective effects. We investigated the ability of wogonin to promote retinal neuron-like differentiation of bone marrow stem cells (BMSCs) and assessed the involvement of Notch-1 signaling in this process. Cultured mouse BMSCs were left untreated or exposed to neurotrophic factors in the presence or absence of wogonin, and western blotting, RT-PCR and immunofluorescence were used to identify changes in molecular markers of stemness and neuroretinal differentiation...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411269/novel-regulatory-mechanisms-for-the-soxc-transcriptional-network-required-for-visual-pathway-development
#6
Kun-Che Chang, Jonathan Hertz, Xiong Zhang, Xiao-Lu Jin, Peter Shaw, Brooke A Derosa, Janet Y Li, Praseeda Venugopalan, Daniel A Valenzuela, Roshni D Patel, Kristina R Russano, Shomoukh A Alshamekh, Catalina Sun, Kevin Tenerelli, Chenyi Li, Dmitri Velmeshev, Yuyan Cheng, Timothy M Boyce, Alexandra Dreyfuss, Mohammed S Uddin, Kenneth J Muller, Derek M Dykxhoorn, Jeffrey L Goldberg
What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor (REST) in regulating RGC fate, and further describe a newly identified, Sox4-regulated SUMOylation site in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system...
April 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28400433/stem-cell-therapies-for-retinal-diseases-recapitulating-development-to-replace-degenerated-cells
#7
REVIEW
Cuiping Zhao, Qingjie Wang, Sally Temple
Retinal degenerative diseases are the leading causes of blindness worldwide. Replacing lost retinal cells via stem cell-based therapies is an exciting, rapidly advancing area of translational research that has already entered the clinic. Here, we review the status of these clinical efforts for several significant retinal diseases, describe the challenges involved and discuss how basic developmental studies have contributed to and are needed to advance clinical goals.
April 15, 2017: Development
https://www.readbyqxmd.com/read/28396597/photoreceptor-outer-segment-like-structures-in-long-term-3d-retinas-from-human-pluripotent-stem-cells
#8
Karl J Wahlin, Julien A Maruotti, Srinivasa R Sripathi, John Ball, Juan M Angueyra, Catherine Kim, Rhonda Grebe, Wei Li, Bryan W Jones, Donald J Zack
The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28395800/derivation-and-characterization-of-the-human-embryonic-stem-cell-line-cr-4-differentiation-to-human-retinal-pigment-epithelial-cells
#9
John L Mazzilli, Aleksey Y Domozhirov, Stacey L Mueller-Ortiz, Charles A Garcia, Rick A Wetsel, Eva M Zsigmond
The CR-4 human embryonic stem cell line was derived from the inner cell mass of a developing blastocyst. This cell line has been adapted to grow in feeder-free conditions and is especially well-suited for differentiation to retinal pigment epithelium. The line demonstrates a normal human 46,XX female karyotype. Pluripotency was assessed through qRT-PCR for expression of NANOG, OCT-4, and SOX-2. A teratoma assay was performed and results were positive for all three germ layers. Testing for Mycoplasma was negative...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28390992/patient-specific-induced-pluripotent-stem-cells-to-evaluate-the-pathophysiology-of-trnt1-associated-retinitis-pigmentosa
#10
Tasneem P Sharma, Luke A Wiley, S Scott Whitmore, Kristin R Anfinson, Cathryn M Cranston, Douglas J Oppedal, Heather T Daggett, Robert F Mullins, Budd A Tucker, Edwin M Stone
Retinitis pigmentosa (RP) is a heterogeneous group of monogenic disorders characterized by progressive death of the light-sensing photoreceptor cells of the outer neural retina. We recently identified novel hypomorphic mutations in the tRNA Nucleotidyl Transferase, CCA-Adding 1 (TRNT1) gene that cause early-onset RP. To model this disease in vitro, we generated patient-specific iPSCs and iPSC-derived retinal organoids from dermal fibroblasts of patients with molecularly confirmed TRNT1-associated RP. Pluripotency was confirmed using rt-PCR, immunocytochemistry, and a TaqMan Scorecard Assay...
March 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28384031/polarized-secretion-of-matrix-metalloproteinases-and-their-inhibitors-by-retinal-pigment-epithelium-derived-from-induced-pluripotent-stem-cells-during-wound-healing
#11
Whitney A Greene, Teresa A Burke, Ramesh R Kaini, Elaine D Por, Heuy-Ching Wang
PURPOSE: To characterize the secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) by induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. We hypothesize that iPS-RPE secretes mediators of tissue remodeling such as MMPs and TIMPs to promote migration and proliferation of cells during wound healing. METHODS: iPS-RPE was grown on transwells until fully confluent and pigmented...
April 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28376025/simultaneous-keratolimbal-autograft-and-penetrating-autokeratoplasty-a-single-stage-procedure-to-restore-monocular-vision-of-a-blind-patient-with-limbal-stem-cell-deficiency
#12
Elias Jarade, Mazen Amro, Ali A Haydar, Adib Hemade
PURPOSE: To describe the technique of simultaneous keratolimbal autograft and penetrating autokeratoplasty to restore monocular vision of a blind patient with limbal stem cell deficiency (LSCD). METHODS: A patient with acquired monocular vision due to loss of the left eye owing to LSCD postblast injury presented with acute loss of vision in the right eye due to central retinal artery occlusion. Simultaneous keratolimbal autograft and penetrating autokeratoplasty were performed in attempt to restore his vision in the left eye...
April 3, 2017: Cornea
https://www.readbyqxmd.com/read/28371543/upregulation-of-matrix-metalloproteinase-triggers-transdifferentiation-of-retinal-pigmented-epithelial-cells-in-xenopus-laevis-a-link-between-inflammatory-response-and-regeneration
#13
Hanako Naitoh, Yukari Suganuma, Yoko Ueda, Takahiko Sato, Yosuke Hiramuki, Atsuko Fujisawa-Sehara, Shigeru Taketani, Masasuke Araki
In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, we examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid...
April 2, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28370142/morphological-study-of-a-connexin-43-gfp-reporter-mouse-highlights-glial-heterogeneity-amacrine-cells-and-olfactory-ensheathing-cells
#14
Panos Theofilas, Christian Steinhäuser, Martin Theis, Amin Derouiche
Connexin 43 (Cx43) is the main astrocytic connexin and forms the basis of the glial syncytium. The morphology of connexin-expressing cells can be best studied in transgenic mouse lines expressing cytoplasmic fluorescent reporters, since immunolabeling the plaques can obscure the shapes of the individual cells. The Cx43kiECFP mouse generated by Degen et al. (FASEBJ 26:4576, 2012) expresses cytosolic ECFP and has previously been used to establish that Cx43 may not be expressed by all astrocytes within a population, and this can vary in a region-dependent way...
March 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28368496/characterization-of-human-cytomegalovirus-genome-diversity-in-immunocompromised-hosts-by-whole-genomic-sequencing-directly-from-clinical-specimens
#15
E Hage, G S Wilkie, S Linnenweber-Held, A Dhingra, N M Suárez, J J Schmidt, P Kay-Fedorov, E Mischak-Weissinger, A Heim, A Schwarz, T F Schulz, A J Davison, T Ganzenmueller
Background: Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals. Methods: NGS was performed on target-enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast-milk, respiratory samples, biopsies and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients and congenitally infected children)...
March 27, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28361307/generation-of-a-three-dimensional-retinal-tissue-from-self-organizing-human-esc-culture
#16
Atsushi Kuwahara, Tokushige Nakano, Mototsugu Eiraku
A three-dimensional (3D) tissue generated in vitro is a promising source to study developmental biology and regenerative medicine. In the last decade, Yoshiki Sasai's group have developed a 3D stem cell culture technique known as SFEBq and demonstrated that embryonic stem cells (ESCs) have an ability to self-organize stratified neural tissue including 3D-retina. Furthermore, we have reported that ESC-derived retinal tissue can form an optic cup and a ciliary margin, which are unique structures in the developing retina...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28355662/-photoreceptor-transplantation-into-the-degenerative-retina
#17
O Borsch, T Santos-Ferreira, M Ader
Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed to repair vision loss, including cell-based interventions. Within the last decade, major progress regarding the replacement of photoreceptors by transplantation has been made in pre-clinical animal models...
March 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28351682/two-photon-polymerization-for-production-of-human-ipsc-derived-retinal-cell-grafts
#18
Kristan S Worthington, Luke A Wiley, Emily E Kaalberg, Malia M Collins, Robert F Mullins, Edwin M Stone, Budd A Tucker
Recent advances in induced pluripotent stem cell (iPSC) technology have paved the way for the production of patient-specific neurons that are ideal for autologous cell replacement for treatment of neurodegenerative diseases. In the case of retinal degeneration and associated photoreceptor cell therapy, polymer scaffolds are critical for cellular survival and integration; however, prior attempts to materialize this concept have been unsuccessful in part due to the materials' inability to guide cell alignment...
March 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28351499/retina-tissue-engineering-by-conjunctiva-mesenchymal-stem-cells-encapsulated-in-fibrin-gel-hypotheses-on-novel-approach-to-retinal-diseases-treatment
#19
Mostafa Soleimannejad, Somayeh Ebrahimi-Barough, Samad Nadri, Mohammad Riazi-Esfahani, Masoud Soleimani, Seyed Mohammad Tavangar, Jafar Ai
BACKGROUND: Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision. PRESENTATION OF THE HYPOTHESIS: Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28345876/engineering-cellular-microenvironments-with-photo-and-enzymatically-responsive-hydrogels-toward-biomimetic-3d-cell-culture-models
#20
Roger Y Tam, Laura J Smith, Molly S Shoichet
Conventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as cell proliferation, differentiation, and cell-cell interactions. However, the physical and chemical properties of 2D culture in vitro are dramatically different than those found in the native cellular microenvironment in vivo. Cells grown on 2D substrates differ significantly from those grown in vivo, and this explains, in part, why many promising drug candidates discovered through in vitro drug screening assays fail when they are translated to in vivo animal or human models...
March 27, 2017: Accounts of Chemical Research
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