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https://www.readbyqxmd.com/read/28089909/immunosuppression-via-loss-of-il2r%C3%AE-enhances-long-term-functional-integration-of-hesc-derived-photoreceptors-in-the-mouse-retina
#1
Jie Zhu, Helen Cifuentes, Joseph Reynolds, Deepak A Lamba
Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells...
December 29, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28086806/age-related-macular-degeneration-associated-polymorphism-rs10490924-in-arms2-results-in-deficiency-of-a-complement-activator
#2
Sven Micklisch, Yuchen Lin, Saskia Jacob, Marcus Karlstetter, Katharina Dannhausen, Prasad Dasari, Monika von der Heide, Hans-Martin Dahse, Lisa Schmölz, Felix Grassmann, Medhanie Alene, Sascha Fauser, Harald Neumann, Stefan Lorkowski, Diana Pauly, Bernhard H Weber, Antonia M Joussen, Thomas Langmann, Peter F Zipfel, Christine Skerka
BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The polymorphism rs10490924 in the ARMS2 gene is highly associated with AMD and linked to an indel mutation (del443ins54), the latter inducing mRNA instability. At present, the function of the ARMS2 protein, the exact cellular sources in the retina and the biological consequences of the rs10490924 polymorphism are unclear. METHODS: Recombinant ARMS2 was expressed in Pichia pastoris, and protein functions were studied regarding cell surface binding and complement activation in human serum using fluoresence-activated cell sorting (FACS) as well as laser scanning microscopy (LSM)...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28076757/ipsc-derived-retina-transplants-improve-vision-in-rd1-end-stage-retinal-degeneration-mice
#3
Michiko Mandai, Momo Fujii, Tomoyo Hashiguchi, Genshiro A Sunagawa, Shinichiro Ito, Jianan Sun, Jun Kaneko, Junki Sho, Chikako Yamada, Masayo Takahashi
Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration. However, cell-based therapies for end-stage degenerative retinas that have lost the outer nuclear layer (ONL) are still a big challenge. In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28060316/an-alternative-and-validated-injection-method-for-accessing-the-subretinal-space-via-a-transcleral-posterior-approach
#4
Sachin Parikh, Andrew Le, Julian Davenport, Michael B Gorin, Steven Nusinowitz, Anna Matynia
Subretinal injections have been successfully used in both humans and rodents to deliver therapeutic interventions of proteins, viral agents, and cells to the interphotoreceptor/subretinal compartment that has direct exposure to photoreceptors and the retinal pigment epithelium (RPE). Subretinal injections of plasminogen as well as recent preclinical and clinical trials have demonstrated safety and/or efficacy of delivering viral vectors and stem cells to individuals with advanced retinal disease. Mouse models of retinal disease, particularly hereditary retinal dystrophies, are essential for testing these therapies...
December 7, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28038685/grafted-c-kit-ssea1-eye-wall-progenitor-cells-delay-retinal-degeneration-in-mice-by-regulating-neural-plasticity-and-forming-new-graft-to-host-synapses
#5
Xi Chen, Zehua Chen, Zhengya Li, Chen Zhao, Yuxiao Zeng, Ting Zou, Caiyun Fu, Xiaoli Liu, Haiwei Xu, Zheng Qin Yin
BACKGROUND: Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28011038/msx1-positive-progenitors-in-the-retinal-ciliary-margin-give-rise-to-both-neural-and-non-neural-progenies-in-mammals
#6
Marie-Claude Bélanger, Benoit Robert, Michel Cayouette
In lower vertebrates, stem/progenitor cells located in a peripheral domain of the retina, called the ciliary margin zone (CMZ), cooperate with retinal domain progenitors to build the mature neural retina. In mammals, it is believed that the CMZ lacks neurogenic potential and that the retina develops from one pool of multipotent retinal progenitor cells (RPCs). Here we identify a population of Msx1-expressing progenitors in the mouse CMZ that is both molecularly and functionally distinct from RPCs. Using genetic lineage tracing, we report that Msx1 progenitors have unique developmental properties compared with RPCs...
December 18, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27986614/overview-of-retinal-differentiation-potential-of-mesenchymal-stem-cells-a-promising-approach-for-retinal-cell-therapy
#7
REVIEW
Hossein Salehi, Noushin Amirpour, Shahnaz Razavi, Ebrahim Esfandiari, Reihaneh Zavar
Retinal disease caused by retinal cell apoptosis leads to irreversible vision loss. Stem cell investigation efforts have been made to solve and cure retinal disorders. There are several sources of stem cells which have been used in these experiments. Numerous studies demonstrated that transplanted stem cells can migrate into and integrate in different layers of retina. Among these, mesenchymal stem cells (MSCs) were considered a promising source for cell therapy. Here, we review the literature assessing the potential of MSCs to differentiate into retinal cells in vivo and in vitro as well as their clinical application...
December 13, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27943290/isolation-characterization-and-establishment-of-spontaneously-immortalized-cell-line-hrpe-2s-with-stem-cell-properties
#8
Hoda Shams Najafabadi, Zahra-Soheila Soheili, Shahram Samiei, Hamid Ahmadieh, Ehsan Ranaei Pirmardan, Maryam Masoomi
The retinal pigment epithelium is a monolayer of highly specialized pigmented cells located between the neural retina and the Bruch's membrane of the choroid. RPE cells play a crucial role in the maintenance and function of the underlying photoreceptors. This study introduces a spontaneously arising human retinal pigment epithelial cell line, HRPE-2S, which was isolated from primary RPE cell culture of 2 days old male donor. We characterized morphology and functional properties of the new cell line. The immortalized cell line was maintained in culture for more than 70 passages and 240 divisions...
December 12, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27941384/characterization-of-the-corneal-subbasal-nerve-plexus-in-limbal-stem-cell-deficiency
#9
Pichaya Chuephanich, Chantaka Supiyaphun, Carolina Aravena, Tahir Kansu Bozkurt, Fei Yu, Sophie X Deng
PURPOSE: To quantify the changes in the subbasal nerve plexus in patients with limbal stem cell deficiency (LSCD) using in vivo laser scanning confocal microscopy. METHODS: In this retrospective cross-sectional comparative study, confocal images of 51 eyes of 37 patients with LSCD collected between 2010 and 2015 by the Heidelberg Retina Tomograph III Rostock Corneal Module Confocal Microscope were analyzed. Two independent observers evaluated the scans of the central cornea...
December 8, 2016: Cornea
https://www.readbyqxmd.com/read/27935376/mesenchymal-stem-cells-modulate-light-induced-activation-of-retinal-microglia-through-cx3cl1-cx3cr1-signaling
#10
Libin Huang, Guoxing Xu, Jian Guo, Maosong Xie, Lisha Chen, Wei Xu
PURPOSE: To evaluate the effect of CX3CL1/CX3CR1 signaling on the interaction between mesenchymal stem cells (MSCs) and retinal microglia. METHODS: Supernatants of homogenized retina were harvested from light-damaged SD rats (ISHR) to stimulated retinal microglia. Stimulated microglia were cocultured with MSCs, CX3CL1 over-expressing MSCs (CX3CL1-MSCs) or CX3CL1-blocked MSCs (anti-CX3CL1-MSCs) for 24 hours, and their molecular and functional changes were examined...
December 2016: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/27935095/alteration-of-neurotrophic-factors-after-transplantation-of-bone-marrow-derived-lin-ve-stem-cell-in-nmda-induced-mouse-model-of-retinal-degeneration
#11
Neeru Jindal, Avijit Banik, Sudesh Prabhakar, Kim Vaiphie, Akshay Anand
Retinal ganglion cell layer (RGCs) is one of the important layers of retina, depleted in Glaucoma. Loss of RGC neurons is a major cellular mechanism involved in its pathogenesis resulting in severe vision loss. Stem cell therapy has emerged as a potential strategy to arrest the apoptotic loss of RGCs and also replace the degenerative cells in damaged retina. Here, we have investigated the incorporation and survival of mouse bone marrow derived Lin-ve stem cells in N-methyl-d-aspartate (NMDA)-induced mouse model of retinal degeneration...
December 9, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27928464/mesenchymal-stem-cell-therapy-in-retinal-and-optic-nerve-diseases-an-update-of-clinical-trials
#12
REVIEW
Sonia Labrador-Velandia, María Luz Alonso-Alonso, Sara Alvarez-Sanchez, Jorge González-Zamora, Irene Carretero-Barrio, José Carlos Pastor, Iván Fernandez-Bueno, Girish Kumar Srivastava
Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells (MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice...
November 26, 2016: World Journal of Stem Cells
https://www.readbyqxmd.com/read/27924617/cxcl12-sdf-1-dependent-retinal-migration-of-endogenous-bone-marrow-derived-stem-cells-improves-visual-function-after-pharmacologically-induced-retinal-degeneration
#13
Volker Enzmann, Stéphanie Lecaudé, Anna Kruschinski, Axel Vater
Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of retinal degeneration. Mobilization was achieved in GFP-chimera with NOX-A12, a CXC-motif chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF-1)-neutralizing L-aptamer...
December 6, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27911706/using-induced-pluripotent-stem-cells-to-understand-retinal-ciliopathy-disease-mechanisms-and-develop-therapies
#14
REVIEW
David A Parfitt, Amelia Lane, Conor Ramsden, Katarina Jovanovic, Peter J Coffey, Alison J Hardcastle, Michael E Cheetham
The photoreceptor cells in the retina have a highly specialised sensory cilium, the outer segment (OS), which is important for detecting light. Mutations in cilia-related genes often result in retinal degeneration. The ability to reprogramme human cells into induced pluripotent stem cells and then differentiate them into a wide range of different cell types has revolutionised our ability to study human disease. To date, however, the challenge of producing fully differentiated photoreceptors in vitro has limited the application of this technology in studying retinal degeneration...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27876464/m%C3%A3-ller-stem-cell-dependent-retinal-regeneration
#15
REVIEW
Annu Chohan, Usha Singh, Atul Kumar, Jasbir Kaur
Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas...
January 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27868054/unraveling-the-mysteries-of-pre-mrna-splicing-in-the-retina-via-stem-cell-technology
#16
EDITORIAL
Rob W J Collin
No abstract text is available yet for this article.
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27867005/temporal-expression-of-cd184-cxcr4-and-cd171-l1cam-identifies-distinct-early-developmental-stages-of-human-retinal-ganglion-cells-in-embryonic-stem-cell-derived-retina
#17
J G Aparicio, H Hopp, A Choi, J Mandayam Comar, V C Liao, N Harutyunyan, T C Lee
Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS...
November 17, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27856246/reprogramming-of-retinoblastoma-cancer-cells-into-cancer-stem-cells
#18
Fengming Yue, Kanji Hirashima, Daihachiro Tomotsune, Sakiko Takizawa-Shirasawa, Tadayuki Yokoyama, Katsunori Sasaki
Retinoblastoma is the most common intraocular malignancy in pediatric patients. It develops rapidly in the retina and can be fatal if not treated promptly. It has been proposed that a small population of cancer cells, termed cancer stem cells (CSCs), initiate tumorigenesis from immature tissue stem cells or progenitor cells. Reprogramming technology, which can convert mature cells into pluripotent stem cells (iPS), provides the possibility of transducing malignant cancer cells back to CSCs, a type of early stage of cancer...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27826002/3d-culture-of-human-pluripotent-stem-cells-in-rgd-alginate-hydrogel-improves-retinal-tissue-development
#19
Nicola C Hunt, Dean Hallam, Ayesha Karimi, Carla B Mellough, Jinju Chen, David H W Steel, Majlinda Lako
: No treatments exist to effectively treat many retinal diseases. Retinal pigmented epithelium (RPE) and neural retina can be generated from human embryonic stem cells/induced pluripotent stem cells (hESCs/hiPSCs). The efficacy of current protocols is, however, limited. It was hypothesised that generation of laminated neural retina and/or RPE from hiPSCs/hESCs could be enhanced by three dimensional (3D) culture in hydrogels. hiPSC- and hESC-derived embryoid bodies (EBs) were encapsulated in 0...
November 5, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27807930/human-bone-marrow-mesenchymal-stem-cells-for-retinal-vascular-injury
#20
Jin-Da Wang, Ying An, Jing-Shang Zhang, Xiu-Hua Wan, Jost B Jonas, Liang Xu, Wei Zhang
PURPOSE: To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. METHODS: Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally...
November 3, 2016: Acta Ophthalmologica
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