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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/29298421/primary-cilium-mediated-retinal-pigment-epithelium-maturation-is-disrupted-in-ciliopathy-patient-cells
#2
Helen Louise May-Simera, Qin Wan, Balendu Shekhar Jha, Juliet Hartford, Vladimir Khristov, Roba Dejene, Justin Chang, Sarita Patnaik, Quanlong Lu, Poulomi Banerjee, Jason Silver, Christine Insinna-Kettenhofen, Dishita Patel, Mostafa Lotfi, May Malicdan, Nathan Hotaling, Arvydas Maminishkis, Rupa Sridharan, Brian Brooks, Kiyoharu Miyagishima, Meral Gunay-Aygun, Rajarshi Pal, Christopher Westlake, Sheldon Miller, Ruchi Sharma, Kapil Bharti
Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29284513/xeno-and-feeder-free-differentiation-of-human-pluripotent-stem-cells-to-two-distinct-ocular-epithelial-cell-types-using-simple-modifications-of-one-method
#3
Heidi Hongisto, Tanja Ilmarinen, Meri Vattulainen, Alexandra Mikhailova, Heli Skottman
BACKGROUND: Human pluripotent stem cells (hPSCs) provide a promising cell source for ocular cell replacement therapy, but often lack standardized and xenogeneic-free culture and differentiation protocols. We aimed to develop a xeno- and feeder cell-free culture system for undifferentiated hPSCs along with efficient methods to derive ocular therapy target cells: retinal pigment epithelial (RPE) cells and corneal limbal epithelial stem cells (LESCs). METHODS: Multiple genetically distinct hPSC lines were adapted to a defined, xeno-, and feeder-free culture system of Essential 8™ medium and laminin-521 matrix...
December 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29284397/stem-progenitor-cells-and-biodegradable-scaffolds-in-the-treatment-of-retinal-degenerative-diseases
#4
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
#5
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
#6
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/29259527/%C3%A2-potential-of-gene-editing-and-induced-pluripotent-stem-cells-ipscs-in-treatment-of-retinal-diseases%C3%A2
#7
REVIEW
Katherine Chuang, Mark A Fields, Lucian V Del Priore
The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy...
December 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/29244789/pigment-epithelium-derived-factor-from-arpe19-promotes-proliferation-and-inhibits-apoptosis-of-human-umbilical-mesenchymal-stem-cells-in-serum-free-medium
#8
Dah-Ching Ding, Yao-Tseng Wen, Rong-Kung Tsai
Clinical expansion of mesenchymal stem cells (MSCs) is hampered by the lack of knowledge regarding how to prevent MSC apoptosis and promote their proliferation in serum-free medium. Our in vitro studies demonstrated that human umbilical cord MSCs (HUCMSCs) underwent apoptosis in the serum-free medium. When HUCMSCs were co-cultured with retinal pigment epithelial cells (ARPE19), however, HUCMSCs exhibited normal growth and morphology in serum-free medium. Their colony formation was promoted by the conditioned medium (CM) of ARPE19 cells on Matrigel...
December 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29239312/endogenous-retinal-neural-stem-cell-reprogramming-for-neuronal-regeneration
#9
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/29235208/optical-coherence-tomography-for-assessment-of-epithelialization-in-a-human-ex-vivo-wound-model
#10
George D Glinos, Sebastian H Verne, Adam S Aldahan, Liang Liang, Keyvan Nouri, Sharon Elliot, Marilyn Glassberg, Delia Cabrera DeBuc, Tulay Koru-Sengul, Marjana Tomic-Canic, Irena Pastar
The ex vivo human skin wound model is a widely accepted model to study wound epithelialization. Due to a lack of animal models that fully replicate human conditions, the ex vivo model is a valuable tool to study mechanisms of wound re-epithelialization, as well as for pre-clinical testing of novel therapeutics. The current standard for assessment of wound healing in this model is histomorphometric analysis, which is labor intensive, time consuming, and requires multiple biological and technical replicates in addition to assessment of different time points...
December 13, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29233750/fibrin-hydrogels-as-a-xenofree-and-rapidly-degradable-support-for-transplantation-of-retinal-pigment-epithelium-monolayers
#11
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
#12
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
#13
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/29230913/a-novel-approach-to-single-cell-rna-seq-analysis-facilitates-in-silico-gene-reporting-of-human-pluripotent-stem-cell-derived-retinal-cell-types
#14
M Joseph Phillips, Peng Jiang, Sara Howden, Patrick Barney, Jee Min, Nathaniel W York, Li-Fang Chu, Elizabeth E Capowski, Abigail Cash, Shivani Jain, Katherine Barlow, Tasnia Tabassum, Ron Stewart, Bikash R Pattnaik, James A Thomson, David M Gamm
Cell type-specific investigations commonly employ gene reporters or single-cell (sc) analytical techniques. However, reporter line development is arduous and generally limited to a single gene of interest, while scRNA-seq frequently yields equivocal results that preclude definitive cell identification. To examine gene expression profiles of multiple retinal cell types derived from human pluripotent stem cells (hPSCs), we performed scRNA-seq on optic vesicle-like structures (OVs) cultured under cGMP-compatible conditions...
December 12, 2017: Stem Cells
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
#15
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/29207059/therapeutic-effect-of-adipose%C3%A2-derived-stem-cell-transplantation-on-optic-nerve-injury-in-rats
#16
Xu Li, Shanyao Zhao, Liangjun Wang
Adipose-derived stem cells (ADSCs) are mesenchymal stem cells in adipose tissue. ADSCs may differentiate into cells and tissues of different embryonic germ layers under specific inducing conditions. Previous studies have demonstrated that Schwann cells transformed from ADSCs can express nerve growth factors, generate nerve fibers and promote axonal regeneration in models of peripheral nerve injury. Stem cell transplantation is one of the potential techniques for the treatment of retinal ganglion cell injury...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29196712/effects-of-neuroactive-agents-on-axonal-growth-and-pathfinding-of-retinal-ganglion-cells-generated-from-human-stem-cells
#17
Tadashi Yokoi, Taku Tanaka, Emiko Matsuzaka, Fuminobu Tamalu, Shu-Ichi Watanabe, Sachiko Nishina, Noriyuki Azuma
We recently established a novel method for generating functional human retinal ganglion cells (RGCs) from human induced pluripotent cells (hiPSCs). Here, we confirmed that RGCs can also be generated from human embryonic stem cells (hESCs). We investigated the usefulness of human RGCs with long axons for assessing the effects of chemical agents, such as the neurotrophic factor, nerve growth factor (NGF), and the chemorepellent factors, semaphorin 3 A (SEMA3A) and SLIT1. The effects of direct and local administration of each agent on axonal projection were evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and real-time imaging, in which the filopodia of the growth cone served as an excellent marker...
December 1, 2017: Scientific Reports
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
#18
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/29188520/production-of-ips-derived-human-retinal-organoids-for-use-in-transgene-expression-assays
#19
Peter M Quinn, Thilo M Buck, Charlotte Ohonin, Harald M M Mikkers, Jan Wijnholds
In vitro retinal organoid modeling from human pluripotent stem cells is becoming more common place in many ophthalmic laboratories worldwide. These organoids mimic human retinogenesis through formation of organized layered retinal structures that display markers for typical retinal cell types. Pivotally these humanized retinal models provide a stepping stone to the clinic as therapeutic tools and are expected to provide a promising alternative to current animal models. Thus pluripotent stem cell based healthy as well as diseased human retinal organoids are attractive for use in drug potency assays and gene augmentation therapeutics...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29187167/high-ocular-cmv-copies-and-mismatched-receipts-may-predict-poor-visual-prognosis-in-cmv-retinitis-patients-following-allogeneic-haematopoietic-stem-cell-transplantation
#20
Yuehong Zhang, Xiangcai Ruan, Weizhong Yang, Ling Li, Zhuanhua Xian, Qiting Feng, Wenjian Mo
BACKGROUND: To summarize the clinical characteristics and potential factors affecting the visual outcomes in patients with cytomegalovirus retinitis following allogeneic haematopoietic stem cell transplantation (HSCT). METHODS: This retrospective study enrolled 12 patients (19 eyes) with cytomegalovirus retinitis after HSCT at Guangzhou First People's Hospital in China between January 2013 and December 2014. Demographic and clinical characteristics, ocular manifestations and visual outcomes were evaluated by reviewing medical records at the Departments of Hematology and Ophthalmology...
November 29, 2017: BMC Ophthalmology
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