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https://www.readbyqxmd.com/read/29327488/isolation-of-human-photoreceptor-precursors-via-a-cell-surface-marker-panel-from-stem-cell-derived-retinal-organoids-and-fetal-retinae
#1
Jörn Lakowski, Emily Welby, Dimitri Budinger, Fabiana Di Marco, Valentina Di Foggia, James W B Bainbridge, Kyle Wallace, David M Gamm, Robin R Ali, Jane C Sowden
Loss of photoreceptor cells due to retinal degeneration is one of the main causes of blindness in the developed world. Although there is currently no effective treatment, cell replacement therapy using stem-cell-derived photoreceptor cells may be a feasible future treatment option. In order to ensure safety and efficacy of this approach, robust cell isolation and purification protocols must be developed. To this end, we previously developed a biomarker panel for the isolation of mouse photoreceptor precursors from the developing mouse retina and mouse embryonic stem cell cultures...
January 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29307580/transplanted-donor-or-stem-cell-derived-cone-photoreceptors-can-both-integrate-and-undergo-material-transfer-in-an-environment-dependent-manner
#2
Paul V Waldron, Fabiana Di Marco, Kamil Kruczek, Joana Ribeiro, Anna B Graca, Claire Hippert, Nozie D Aghaizu, Aikaterini A Kalargyrou, Amanda C Barber, Giulia Grimaldi, Yanai Duran, Samuel J I Blackford, Magdalena Kloc, Debbie Goh, Eduardo Zabala Aldunate, Robert D Sampson, James W B Bainbridge, Alexander J Smith, Anai Gonzalez-Cordero, Jane C Sowden, Robin R Ali, Rachael A Pearson
Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photoreceptors can restore visual function in models of inherited blindness, a process previously understood to arise by donor cell integration within the host retina. However, we and others recently demonstrated that donor rod photoreceptors engage in material transfer with host photoreceptors, leading to the host cells acquiring proteins otherwise expressed only by donor cells...
January 4, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29284397/stem-progenitor-cells-and-biodegradable-scaffolds-in-the-treatment-of-retinal-degenerative-diseases
#3
Yuyao Wang, Dandan Zhang, Bingqiao Shen, Yi Zhang, Ping Gu
Visual impairment caused by retinal degeneration is primarily attributed to the irreversible degradation of retinal neurons or the adjacent retinal pigment epithelium (RPE). No efficient clinical therapies to restore or improve visual ability are currently available. Cell therapy has been touted as a promising strategy to overcome this challenge. Progenitor/stem cells may be obtained from both ocular and non-ocular tissues. The former mainly includes retinal progenitor cells (RPCs), whereas the latter comprises embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which have been utilized in stem cell replacement therapy studies ranging from proof-of-concept animal models to clinical trials in humans...
December 27, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29274337/generation-of-three-dimensional-retinal-organoids-expressing-rhodopsin-and-s-and-m-cone-opsins-from-mouse-stem-cells
#4
Kaori Ueda, Akishi Onishi, Shin-Ichiro Ito, Makoto Nakamura, Masayo Takahashi
PURPOSE: Three-dimensional retinal organoids can be differentiated from embryonic stem cells/induced pluripotent stem cells (ES/iPS cells) under defined medium conditions. We modified the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) culture procedure to obtain retinal organoids expressing more rod photoreceptors and S- and M-cone opsins. METHODS: Retinal organoids differentiated from mouse Nrl-eGFP iPS cells were cultured in various mediums during photoreceptor development...
December 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29273085/adult-human-periodontal-ligament-derived-stem-cells-delay-retinal-degeneration-and-maintain-retinal-function-in-rcs-rats
#5
Li Huang, Zongyi Li, Haibin Tian, Weiguo Wang, Dawei Cui, Zhe Zhou, Xiao Chen, Herman S Cheung, Guo-Tong Xu, Yu Chen
BACKGROUND: Retinal degeneration (RD) is a leading cause of irreversible blindness, affecting millions of people worldwide. Stem cell transplantation has been considered a promising therapy for retinal degenerative diseases. This study aimed to investigate the therapeutic potential of human periodontal ligament-derived stem cells (hPDLSCs) for intervention in the progress of this degeneration in the Royal College Surgeons (RCS) rat. METHODS: hPDLSCs were injected into the subretinal space of 3-week-old RCS rats...
December 22, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29239312/endogenous-retinal-neural-stem-cell-reprogramming-for-neuronal-regeneration
#6
REVIEW
Romain Madelaine, Philippe Mourrain
In humans, optic nerve injuries and associated neurodegenerative diseases are often followed by permanent vision loss. Consequently, an important challenge is to develop safe and effective methods to replace retinal neurons and thereby restore neuronal functions and vision. Identifying cellular and molecular mechanisms allowing to replace damaged neurons is a major goal for basic and translational research in regenerative medicine. Contrary to mammals, the zebrafish has the capacity to fully regenerate entire parts of the nervous system, including retina...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29233750/fibrin-hydrogels-as-a-xenofree-and-rapidly-degradable-support-for-transplantation-of-retinal-pigment-epithelium-monolayers
#7
Jarel K Gandhi, Zahid Manzar, Lori A Bachman, Cynthia Andrews-Pfannkoch, Travis Knudsen, Matthew Hill, Hannah Schmidt, Raymond Iezzi, Jose S Pulido, Alan D Marmorstein
Recent phase 1 trials of embryonic stem cell and induced pluripotent stem cell (iPSCs) derived RPE transplants for the treatment of macular degeneration have demonstrated the relative safety of this process. However, there is concern over clumping, thickening, folding, and wrinkling of the transplanted RPE. To deliver a flat RPE monolayer, current phase 1 trials are testing synthetic substrates for RPE transplantation. These substrates, however, cause localized inflammation and fibrosis in animal models due to long degradation times...
December 9, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29233554/accelerated-and-improved-differentiation-of-retinal-organoids-from-pluripotent-stem-cells-in-rotating-wall-vessel-bioreactors
#8
Tyler DiStefano, Holly Yu Chen, Christopher Panebianco, Koray Dogan Kaya, Matthew J Brooks, Linn Gieser, Nicole Y Morgan, Tom Pohida, Anand Swaroop
Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV) bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors...
December 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29233477/molecular-anatomy-of-the-developing-human-retina
#9
Akina Hoshino, Rinki Ratnapriya, Matthew J Brooks, Vijender Chaitankar, Matthew S Wilken, Chi Zhang, Margaret R Starostik, Linn Gieser, Anna La Torre, Mario Nishio, Olivia Bates, Ashley Walton, Olivia Bermingham-McDonogh, Ian A Glass, Rachel O L Wong, Anand Swaroop, Thomas A Reh
Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina...
December 1, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29226476/differences-in-the-activity-of-endogenous-bmp-signalling-impact-on-the-ability-of-induced-pluripotent-stem-cells-to-differentiate-to-corneal-epithelial-like-cells
#10
Taty Anna Kamarudin, Sanja Bojic, Joseph Collin, Min Yu, Sameer Alharthi, Harley Buck, Alex Shortt, Lyle Armstrong, Francisco C Figueiredo, Majlinda Lako
Cornea is a clear outermost layer of the eye which enables transmission of light onto the retina. The transparent corneal epithelium is regenerated by limbal stem cells (LSCs), whose loss/dysfunction results in limbal stem cell deficiency (LSCD). Ex vivo expansion of autologous LSCs obtained from patient's healthy eye followed by transplantation onto the LSCs damaged/deficient eye, has provided a successful treatment for unilateral LSCD. This however is not applicable to patient with total bilateral LSCD, where LSCs are lost/damaged from both eyes...
December 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/29217756/light-focusing-human-micro-lenses-derived-from-zebrafish-like-lens-cell-masses-model-lens-development-and-drug-induced-cataract-in-vitro
#11
Patricia Murphy, Md Humayun Kabir, Tarini Srivastava, Michele E Mason, Chitra Umala Dewi, Seakcheng Lim, Andrian Yang, Djordje Djordjevic, Murray C Killingsworth, Joshua W K Ho, David G Harman, Michael D O'Connor
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells...
December 7, 2017: Development
https://www.readbyqxmd.com/read/29210653/human-umbilical-cord-mesenchymal-stem-cells-subpopulations-and-their-difference-in-cell-biology-and-effects-on-retinal-degeneration-in-rcs-rats
#12
L Wang, P Li, Y Tian, Z Li, C Lian, Q Ou, C Jin, F Gao, J-Y Xu, J Wang, F Wang, J Zhang, J Zhang, W Li, H Tian, L Lu, G-T Xu
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). To further study the biology and therapeutic effects of these cells, two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression...
December 5, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29193451/retinoic-acid-signaling-regulates-the-proliferative-and-neurogenic-capacity-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#13
Levi Todd, Lilianna Suarez, Colin Quinn, Andy J Fischer
In the retina, Müller glia have the potential to become progenitor cells with the ability to proliferate and regenerate neurons. However, the ability of Müller glia-derived progenitor cells (MGPCs) to proliferate and produce neurons is limited in higher vertebrates. Using the chick model system, we investigate how retinoic acid (RA)-signaling influences the proliferation and the formation of MGPCs. We observed an upregulation of cellular RA binding proteins (CRABP) in the Müller glia of damaged retinas where the formation of MGPCs is known to occur...
November 27, 2017: Stem Cells
https://www.readbyqxmd.com/read/29167189/photobiodulation-inhibits-long-term-structural-and-functional-lesions-of-diabetic-retinopathy
#14
Yan Cheng, Yunpeng Du, Haitao Liu, Jie Tang, Alex Veenstra, Timothy S Kern
Previous studies demonstrated that brief (3-4 minutes), daily application of light at 670nm to diabetic rodents inhibited molecular and pathophysiologic processes implicated in the pathogenesis of diabetic retinopathy (DR), and reversed diabetic macular edema in small numbers of patients studied. Whether or not this therapy would inhibit the neural and vascular lesions that characterize the early stages of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy daily for 8 months to streptozotocin-diabetic mice, and assessed effects of PBM on visual function, retinal capillary permeability, and capillary degeneration using published methods...
November 22, 2017: Diabetes
https://www.readbyqxmd.com/read/29164803/preclinical-evaluation-and-optimization-of-a-cell-therapy-using-human-cord-blood-derived-endothelial-colony-forming-cells-for-ischemic-retinopathies
#15
Emma Reid, Jasenka Guduric-Fuchs, Christina L O'Neill, Lynsey-Dawn Allen, Sarah E J Chambers, Alan W Stitt, Reinhold J Medina
Cell therapy using endothelial progenitors holds promise for vascular repair in ischemic retinopathies. Using a well-defined subpopulation of human cord blood-derived endothelial progenitors known as endothelial colony-forming cells (ECFCs), we have evaluated essential requirements for further development of this cell therapy targeting the ischemic retina, including dose response, delivery route, and toxicity. First, to evaluate therapeutic efficacy relating to cell dose, ECFCs were injected into the vitreous of mice with oxygen-induced retinopathy...
November 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29161152/proliferative-cells-isolated-from-the-adult-human-peripheral-retina-only-transiently-upregulate-key-retinal-markers-upon-induced-differentiation
#16
Erik O Johnsen, Rebecca C Frøen, Ole Kristoffer Olstad, Bjørn Nicolaissen, Goran Petrovski, Morten C Moe, Agate Noer
Purpose/Aim: The adult human retina has limited regenerative potential, and severe injury will result in permanent damage. Lower vertebrates handle retinal injury by activating neural stem cells (NSCs) in the ciliary marginal zone (CMZ). Müller glia-like cells expressing markers of NSCs are also present in the peripheral retina (PR) of the adult human eye, leading to the hypothesis that a CMZ-like zone might exists also in humans. In order to shed further light on this hypothesis we investigated the in vitro differentiation potential of proliferative cells isolated from the adult human PR towards a retinal phenotype...
November 21, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29153988/isolation-and-comparative-transcriptome-analysis-of-human-fetal-and-ipsc-derived-cone-photoreceptor-cells
#17
Emily Welby, Jorn Lakowski, Valentina Di Foggia, Dimitri Budinger, Anai Gonzalez-Cordero, Aaron T L Lun, Michael Epstein, Aara Patel, Elisa Cuevas, Kamil Kruczek, Arifa Naeem, Federico Minneci, Mike Hubank, David T Jones, John C Marioni, Robin R Ali, Jane C Sowden
Loss of cone photoreceptors, crucial for daylight vision, has the greatest impact on sight in retinal degeneration. Transplantation of stem cell-derived L/M-opsin cones, which form 90% of the human cone population, could provide a feasible therapy to restore vision. However, transcriptomic similarities between fetal and stem cell-derived cones remain to be defined, in addition to development of cone cell purification strategies. Here, we report an analysis of the human L/M-opsin cone photoreceptor transcriptome using an AAV2/9...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29152454/recent-advances-in-retinal-stem-cell-therapy
#18
Sujoy Bhattacharya, Rajashekhar Gangaraju, Edward Chaum
Purpose of review: Progress in stem cell research for blinding diseases over the past decade is now being applied to patients with retinal degenerative diseases and soon perhaps, glaucoma. However, the field still has much to learn about the conversion of stem cells into various retinal cell types, and the potential delivery methods that will be required to optimize the clinical efficacy of stem cells delivered into the eye. Recent findings: Recent groundbreaking human clinical trials have demonstrated both the opportunities and current limitations of stem cell transplantation for retinal diseases...
September 2017: Current Molecular Biology Reports
https://www.readbyqxmd.com/read/29150936/the-roles-of-wnt-%C3%AE-catenin-pathway-in-tissue-development-and-regenerative-medicine
#19
REVIEW
Maryam Majidinia, Javad Aghazadeh, Rana Jahanban-Esfahlani, Bahman Yousefi
Regenerative medicine is a translational field which combines tissue engineering and molecular biology to construct spare organs or help injured or defective tissues to regenerate or restore their normal functions. This is particularly important with specific organs such as heart, central nervous system, retina or limbs which possess very limited regenerative capacity. As such, regenerative medicine has received peculiar attention in the last decade. In this regard, Wnt/β-catenin signaling pathway has been subject to intensive research, since it plays many essential roles in the regulation of the progenitor cell fate, developmental decisions, proliferation during embryonic development, and adult tissue homeostasis...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29130158/crispr-in-the-retina-evaluation-of-future-potential
#20
Galaxy Y Cho, Sally Justus, Jesse D Sengillo, Stephen H Tsang
Clustered regularly interspaced short palindromic repeats (CRISPR) has been gaining widespread attention for its ability for targeted genome surgery. In treating inherited retinal degenerations, gene therapies have had varied results; the ones effective in restoring eye sight are limited by transiency in its effect. Genome surgery, however, is a solution that could potentially provide the eye with permanent healthy cells. As retinal degenerations are irreversible and the retina has little regenerative potential, permanent healthy cells are vital for vision...
2017: Advances in Experimental Medicine and Biology
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