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Retinal stem cells

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https://www.readbyqxmd.com/read/28315291/perspectives-of-stem-cell-based-therapy-for-age-related-retinal-degenerative-diseases
#1
Vladimir Holan, Barbora Hermankova, Jan Kossl
Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and glaucoma, mostly affect the elderly population, and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell-based therapy which could replace diseased or missing retinal cells, and support regeneration...
March 17, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28299008/intravitreal-injection-of-bone-marrow-mesenchymal-stem-cells-in-patients-with-advanced-retinitis-pigmentosa-a-safety-study
#2
Leila Satarian, Ramin Nourinia, Sare Safi, Mozhgan Rezaei Kanavi, Neda Jarughi, Narsis Daftarian, Leila Arab, Nasser Aghdami, Hamid Ahmadieh, Hossein Baharvand
PURPOSE: To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). METHODS: A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs...
January 2017: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/28298640/combined-transplantation-of-human-mesenchymal-stem-cells-and-human-retinal-progenitor-cells-into-the-subretinal-space-of-rcs-rats
#3
Linghui Qu, Lixiong Gao, Haiwei Xu, Ping Duan, Yuxiao Zeng, Yong Liu, Zheng Qin Yin
Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296617/vision-loss-after-intravitreal-injection-of-autologous-stem-cells-for-amd
#4
Ajay E Kuriyan, Thomas A Albini, Justin H Townsend, Marianeli Rodriguez, Hemang K Pandya, Robert E Leonard, M Brandon Parrott, Philip J Rosenfeld, Harry W Flynn, Jeffrey L Goldberg
Adipose tissue-derived "stem cells" have been increasingly used by "stem-cell clinics" in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue-derived "stem cells" at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients' severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation...
March 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28296613/autologous-induced-stem-cell-derived-retinal-cells-for-macular-degeneration
#5
Michiko Mandai, Akira Watanabe, Yasuo Kurimoto, Yasuhiko Hirami, Chikako Morinaga, Takashi Daimon, Masashi Fujihara, Hiroshi Akimaru, Noriko Sakai, Yumiko Shibata, Motoki Terada, Yui Nomiya, Shigeki Tanishima, Masahiro Nakamura, Hiroyuki Kamao, Sunao Sugita, Akishi Onishi, Tomoko Ito, Kanako Fujita, Shin Kawamata, Masahiro J Go, Chikara Shinohara, Ken-Ichiro Hata, Masanori Sawada, Midori Yamamoto, Sachiko Ohta, Yasuo Ohara, Kenichi Yoshida, Junko Kuwahara, Yuko Kitano, Naoki Amano, Masafumi Umekage, Fumiyo Kitaoka, Azusa Tanaka, Chihiro Okada, Naoko Takasu, Seishi Ogawa, Shinya Yamanaka, Masayo Takahashi
We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients...
March 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28287872/development-of-a-modular-automated-system-for-maintenance-and-differentiation-of-adherent-human-pluripotent-stem-cells
#6
Duncan E Crombie, Maciej Daniszewski, Helena H Liang, Tejal Kulkarni, Fan Li, Grace E Lidgerwood, Alison Conquest, Damian Hernández, Sandy S Hung, Katherine P Gill, Elisabeth De Smit, Lisa S Kearns, Linda Clarke, Valentin M Sluch, Xitiz Chamling, Donald J Zack, Raymond C B Wong, Alex W Hewitt, Alice Pébay
Patient-specific induced pluripotent stem cells (iPSCs) have tremendous potential for development of regenerative medicine, disease modeling, and drug discovery. However, the processes of reprogramming, maintenance, and differentiation are labor intensive and subject to intertechnician variability. To address these issues, we established and optimized protocols to allow for the automated maintenance of reprogrammed somatic cells into iPSCs to enable the large-scale culture and passaging of human pluripotent stem cells (PSCs) using a customized TECAN Freedom EVO...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28286868/a-basis-for-comparison-sensitive-authentication-of-stem-cell-derived-rpe-using-physiological-responses-of-intact-rpe-monolayers
#7
Kiyoharu J Miyagishima, Qin Wan, Sheldon S Miller, Kapil Bharti
The retinal pigment epithelium (RPE) is a monolayer of highly specialized cells that help maintain the chemical composition of its surrounding subretinal and choroidal extracellular spaces. Retinal cells (photoreceptors in particular), RPE, and choroidal endothelial cells together help ensure a homeostatically stable metabolic environment with exquisitely sensitive functional responses to light. Aging and disease of the RPE impairs its supportive functions contributing to the progressive loss of photoreceptors and vision...
2017: Stem Cell and Translational Investigation
https://www.readbyqxmd.com/read/28285324/novel-therapeutics-for-stargardt-disease
#8
REVIEW
Louise J Lu, Ji Liu, Ron A Adelman
DESCRIPTION OF SITUATION: Stargardt disease, an inherited macular dystrophy caused by mutations in the ABCA4 gene encoding a retinal transporter protein, is the most prevalent form of macular degeneration in children. Patients with Stargardt disease develop severe vision loss within their first or second decades of life, which progresses to irreversible decreased visual acuity in almost all cases. Presently, there are no standard treatments for Stargardt disease. However, encouraging progress has been made in the development of innovative approaches to preventing vision loss in Stargardt patients...
March 11, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28282420/generation-of-retinal-pigmented-epithelium-from-ipscs-derived-from-the-conjunctiva-of-donors-with-and-without-age-related-macular-degeneration
#9
Zhouhui Geng, Patrick J Walsh, Vincent Truong, Caitlin Hill, Mara Ebeling, Rebecca J Kapphahn, Sandra R Montezuma, Ching Yuan, Heidi Roehrich, Deborah A Ferrington, James R Dutton
Fidelity in pluripotent stem cell differentiation protocols is necessary for the therapeutic and commercial use of cells derived from embryonic and induced pluripotent stem cells. Recent advances in stem cell technology, especially the widespread availability of a range of chemically defined media, substrates and differentiation components, now allow the design and implementation of fully defined derivation and differentiation protocols intended for replication across multiple research and manufacturing locations...
2017: PloS One
https://www.readbyqxmd.com/read/28258388/smad7-deficiency-stimulates-m%C3%A3-ller-progenitor-cell-proliferation-during-the-development-of-the-mammalian-retina
#10
Martina Kugler, Anja Schlecht, Rudolf Fuchshofer, Sabrina I Schmitt, Ingo Kleiter, Ludwig Aigner, Ernst R Tamm, Barbara M Braunger
The transforming growth factor-β (TGF-β) pathway contributes to maintain the quiescence of adult neural stem and progenitor cells in the brain. In the retina, Müller cells are discussed to represent a glial cell population with progenitor-like characteristics. Here, we aimed to investigate if elevated TGF-β signaling modulates the proliferation of Müller cells during retinal development. We generated mutant mice with a systemic, heterozygous up-regulation of TGF-β signaling by deleting its inhibitor SMAD7...
March 3, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28256796/human-limbal-neurospheres-prevent-photoreceptor-cell-death-in-a-rat-model-of-retinal-degeneration
#11
Samuel McLenachan, Dan Zhang, Erwei Hao, Ling Zhang, Shang-Chih Chen, Fred K Chen
BACKGROUND: The culture of retinal progenitors from an accessible adult stem cell source such as the limbus could provide a useful autologous source of retinal cell therapies. The human corneoscleral limbus contains multipotent stem cells that can be cultured as floating neurospheres. Previous work in rodents has demonstrated neuronal and photoreceptor differentiation from limbal neurosphere cultures. Here, we have examined undifferentiated cultured adult human limbal neurospheres as donor cells for retinal cell therapies by transplantation into a rat model of retinal degeneration...
March 3, 2017: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/28255307/overexpression-of-heme-oxygenase-1-in-mesenchymal-stem-cells-augments-their-protection-on-retinal-cells-in-vitro-and-attenuates-retinal-ischemia-reperfusion-injury-in-vivo-against-oxidative-stress
#12
Li Li, GaiPing Du, DaJiang Wang, Jin Zhou, Guomin Jiang, Hua Jiang
Retinal ischemia/reperfusion (I/R) injury, involving several ocular diseases, seriously threatens human ocular health, mainly treated by attenuating I/R-induced oxidative stress. Currently, mesenchymal stem cells (MSCs) could restore I/R-injured retina through paracrine secretion. Additionally, heme oxygenase-1 (HO-1) could ameliorate oxidative stress and thus retinal apoptosis, but the expression of HO-1 in MSC is limited. Here, we hypothesized that overexpression of HO-1 in MSC (MSC-HO-1) may significantly improve their retina-protective potentials...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28253236/coordinated-generation-of-multiple-ocular-like-cell-lineages-and-fabrication-of-functional-corneal-epithelial-cell-sheets-from-human-ips-cells
#13
Ryuhei Hayashi, Yuki Ishikawa, Ryousuke Katori, Yuzuru Sasamoto, Yuki Taniwaki, Hiroshi Takayanagi, Motokazu Tsujikawa, Kiyotoshi Sekiguchi, Andrew J Quantock, Kohji Nishida
We describe a protocol for the generation of a functional and transplantable corneal epithelium derived from human induced pluripotent stem (iPS) cells. When this protocol is followed, a proportion of iPS cells spontaneously form circular colonies, each of which is composed of four concentric zones. Cells in these zones have different morphologies and immunostaining characteristics, resembling neuroectoderm, neural crest, ocular-surface ectoderm, or surface ectoderm. We have named this 2D colony a 'SEAM' (self-formed ectodermal autonomous multizone), and previously demonstrated that cells within the SEAM have the potential to give rise to anlages of different ocular lineages, including retinal cells, lens cells, and ocular-surface ectoderm...
April 2017: Nature Protocols
https://www.readbyqxmd.com/read/28249091/subretinal-glial-membranes-in-eyes-with-geographic-atrophy
#14
Malia M Edwards, D Scott McLeod, Imran A Bhutto, Rhonda Grebe, Maeve Duffy, Gerard A Lutty
Purpose: Müller cells create the external limiting membrane (ELM) by forming junctions with photoreceptor cells. This study evaluated the relationship between focal photoreceptors and RPE loss in geographic atrophy (GA) and Müller cell extension into the subretinal space. Methods: Human donor eyes with no retinal disease or geographic atrophy (GA) were fixed and the eye cups imaged. The retinal posterior pole was stained for glial fibrillary acidic protein (GFAP; astrocytes and activated Müller cells) and vimentin (Müller cells) while the submacular choroids were labeled with Ulex Europaeus Agglutinin lectin (blood vessels)...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28248742/central-retinal-vein-occlusion-in-gata2-deficiency
#15
Duncan Berry, Sharon Fekrat
PURPOSE: To examine the association between GATA2 deficiency-related myelodysplastic syndrome (MDS) and central retinal vein occlusion (CRVO). METHODS: Clinical ophthalmologic examination and laboratory work-up was performed for a patient with GATA2 deficiency-related MDS who experienced a unilateral CRVO. The literature was reviewed for reports of CRVO in the setting of MDS and allogeneic hematopoietic stem cell transplantation. RESULTS: Ophthalmologic examination revealed findings consistent with unilateral CRVO...
February 28, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28246391/rescue-of-the-mertk-phagocytic-defect-in-a-human-ipsc-disease-model-using-translational-read-through-inducing-drugs
#16
Conor M Ramsden, Britta Nommiste, Amelia R Lane, Amanda-Jayne F Carr, Michael B Powner, Matthew J K Smart, Li Li Chen, Manickam N Muthiah, Andrew R Webster, Anthony T Moore, Michael E Cheetham, Lyndon da Cruz, Peter J Coffey
Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28241319/integration-of-subretinal-suspension-transplants-of-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells-in-a-large-eyed-model-of-geographic-atrophy
#17
Sandra Petrus-Reurer, Hammurabi Bartuma, Monica Aronsson, Sofie Westman, Fredrik Lanner, Helder André, Anders Kvanta
Purpose: Subretinal suspension transplants of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) have the capacity to form functional monolayers in naive eyes. We explore hESC-RPE integration when transplanted in suspension to a large-eyed model of geographic atrophy (GA). Methods: Derivation of hESC-RPE was performed in a xeno-free and defined manner. Subretinal bleb injection of PBS or sodium iodate (NaIO3) was used to induce a GA-like phenotype...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28223209/langmuir-schaefer-film-deposition-onto-honeycomb-porous-films-for-retinal-tissue-engineering
#18
Maria Teresa Calejo, Tanja Ilmarinen, Elina Vuorimaa-Laukkanen, Elina Talvitie, Hanna M Hakola, Heli Skottman, Minna Kellomäki
Age-related macular degeneration (AMD) is the leading cause of vision loss in senior citizens in the developed world. The disease is characterised by the degeneration of a specific cell layer at the back of the eye - the retinal pigment epithelium (RPE), which is essential in retinal function. The most promising therapeutic option to restore the lost vision is considered to be RPE cell transplantation. This work focuses on the development of biodegradable biomaterials with similar properties to the native Bruch's membrane as carriers for RPE cells...
February 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28220575/generation-of-storable-retinal-organoids-and-retinal-pigmented-epithelium-from-adherent-human-ips-cells-in-xeno-free-and-feeder-free-conditions
#19
Sacha Reichman, Amélie Slembrouck, Giuliana Gagliardi, Antoine Chaffiol, Angélique Terray, Céline Nanteau, Anais Potey, Morgane Belle, Oriane Rabesandratana, Jens Duebel, Gael Orieux, Emeline F Nandrot, José-Alain Sahel, Olivier Goureau
Human induced pluripotent stem cells (hiPSCs) are potentially useful in regenerative therapies for retinal disease. For medical applications, therapeutic retinal cells, such as retinal pigmented epithelial (RPE) cells or photoreceptor precursors, must be generated under completely defined conditions. To this purpose, we have developed a two-step xeno-free/feeder-free (XF/FF) culture system to efficiently differentiate hiPSCs into retinal cells. This simple method, relies only on adherent hiPSCs cultured in chemically defined media, bypassing embryoid body formation...
February 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28220544/prospective-purification-and-characterization-of-m%C3%A3-ller-glia-in-the-mouse-retina-regeneration-assay
#20
Patrick Schäfer, Mike O Karl
Reactive gliosis is an umbrella term for various glia functions in neurodegenerative diseases and upon injury. Specifically, Müller glia (MG) in some species readily regenerate retinal neurons to restore vision loss after insult, whereas mammalian MG respond by reactive gliosis-a heterogeneous response which frequently includes cell hypertrophy and proliferation. Limited regeneration has been stimulated in mammals, with a higher propensity in young MG, and in vitro compared to in vivo, but the underlying processes are unknown...
February 21, 2017: Glia
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