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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/28076757/ipsc-derived-retina-transplants-improve-vision-in-rd1-end-stage-retinal-degeneration-mice
#2
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/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
#3
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/28028920/the-influence-of-substrate-modulus-on-retinal-pigment-epithelial-cells
#4
Corina White, Tyler DiStefano, Ronke Olabisi
Although transplantation of retinal pigment epithelial (RPE) cells has shown promise for the treatment of retinal degenerative diseases, this therapeutic approach is not without challenges. Two major challenges are RPE cell dedifferentiation and inflammatory response following transplantation. The aim of this work is to understand how the rigidity of a scaffold, a relatively unexplored design aspect in retinal tissue engineering, affects RPE cells, particularly the pathways associated with the aforementioned challenges...
December 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28003788/multimodal-imaging-of-membranoproliferative-glomerulonephritis-type-ii
#5
Zafer Cebeci, Serife Bayraktar, Merih Oray, Nur Kir
To report the fundus findings on multimodal imaging of a membranoproliferative glomerulonephritis type II (MPGNII) patient. A 41-year-old woman had a medical history of renal transplantation for MPGNII 5 years prior to presentation to our clinic for ophthalmic examination. Fundus examination showed macular retinal pigment epithelial changes and large peripapillary atrophy in the right eye, and yellowish bilateral drusen-like deposits peripherally. Fundus fluorescein angiography and indocyanine green angiography revealed multifocal hyperfluorescence in the peripheral retina with accompanying deposits...
October 2016: Saudi Journal of Ophthalmology: Official Journal of the Saudi Ophthalmological Society
https://www.readbyqxmd.com/read/28002569/protective-role-of-icos-and-icos-ligand-in-corneal-transplantation-and-in-maintenance-of-immune-privilege
#6
Tomoyuki Kunishige, Hiroko Taniguchi, Misao Terada, Hisaya Akiba, Hideo Yagita, Ryo Abe, Junko Hori
Purpose: The interaction between the inducible costimulatory molecule (ICOS) and ICOS ligand (ICOSL) has been implicated in the differentiation and functions of T cells. The purpose of the present study was to determine the role of ICOS-ICOSL in the immune privilege of corneal allografts. Methods: Expression of ICOS and ICOSL mRNA from mouse eyes was assessed by RT-PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of ICOS-/- BALB/c recipients and BALB/c wild-type (WT) recipients treated with anti-ICOSL mAb, and graft survival was assessed...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27990359/effect-of-endothelial-progenitor-cells-derived-from-human-umbilical-cord-blood-on-oxygen-induced-retinopathy-in-mice-by-intravitreal-transplantation
#7
Dan Wang, Bo Zhang, Hui Shi, Wei Yang, Ming-Chao Bi, Xiang-Fu Song, Chen Zhang, Jian-Hui Cheng, Ji-Long Hao, E Song
AIM: To investigate the effect of endothelial progenitor cells (EPCs) labeled by carboxy fluorescein diacetate succinimidyl ester (CFSE) on murine oxygen-induced retinopathy (OIR) by intravitreal transplantation. METHODS: After isolated from human umbilical cord blood mononuclear cells, EPCs were cultivated and then labeled with CFSE in vitro. C57BL/6J mice were placed to 75% hyperoxia chamber from P7 to P12 to establish OIR model. At P12, OIR mice were intravitreally injected with 1 µL suspension contained 2×10(5) EPCs (EPCs group) or isometric phosphate buffered saline (PBS group)...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27986614/overview-of-retinal-differentiation-potential-of-mesenchymal-stem-cells-a-promising-approach-for-retinal-cell-therapy
#8
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/27977075/a-re-interpretation-of-cell-transplantation-gfp-transfer-from-donor-to-host-photoreceptors
#9
Arturo Ortin-Martinez, En Leh Samuel Tsai, Philip E Nickerson, Miriam Bergeret, Yao Lu, Sheila Smiley, Lacrimioara Comanita, Valerie A Wallace
The utilization of fluorescent reporter transgenes to discriminate donor versus host cells has been a mainstay of photoreceptor transplantation research, the assumption being that the presence of reporter+ cells in outer nuclear layer (ONL) of transplant recipients represents the integration of donor photoreceptors. We previously reported that GFP(+) cells in the ONL of cone-GFP transplanted retinas exhibited rod-like characteristics, raising the possibility that GFP signal in recipient tissue may not be a consequence of cell integration...
December 14, 2016: Stem Cells
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
#10
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/27901042/transplanted-photoreceptor-precursors-transfer-proteins-to-host-photoreceptors-by-a-mechanism-of-cytoplasmic-fusion
#11
Mandeep S Singh, Jasmin Balmer, Alun R Barnard, Sher A Aslam, Daniela Moralli, Catherine M Green, Alona Barnea-Cramer, Isabel Duncan, Robert E MacLaren
Photoreceptor transplantation is a potential future treatment for blindness caused by retinal degeneration. Photoreceptor transplantation restores visual responses in end-stage retinal degeneration, but has also been assessed in non-degenerate retinas. In the latter scenario, subretinal transplantation places donor cells beneath an intact host outer nuclear layer (ONL) containing host photoreceptors. Here we show that host cells are labelled with the donor marker through cytoplasmic transfer-94±4.1% of apparently well-integrated donor cells containing both donor and host markers...
November 30, 2016: Nature Communications
https://www.readbyqxmd.com/read/27834728/graft-versus-self-gvs-against-t-cell-autoantigens-is-a-mechanism-of-graft-host-interaction
#12
Nora Mirza, Manfred Zierhut, Andreas Korn, Antje Bornemann, Wichard Vogel, Barbara Schmid-Horch, Wolfgang A Bethge, Stefan Stevanović, Helmut R Salih, Lothar Kanz, Hans-Georg Rammensee, Sebastian P Haen
Graft-versus-host disease (GVHD) represents the major nonrelapse complication of allogeneic hematopoietic cell transplantation. Although rare, the CNS and the eye can be affected. In this study, manifestation in the retina as part of the CNS and T-cell epitopes recognized by the allogeneic T cells were evaluated. In 2 of 6 patients with posttransplantation retina diseases and 6 of 22 patients without ocular symptoms, antigen-specific T-cell responses against retina-specific epitopes were observed. No genetic differences between donor and recipient could be identified indicating T-cell activation against self-antigens (graft versus self)...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27826002/3d-culture-of-human-pluripotent-stem-cells-in-rgd-alginate-hydrogel-improves-retinal-tissue-development
#13
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/27809828/neonatal-disease-environment-limits-the-efficacy-of-retinal-transplantation-in-the-lca8-mouse-model
#14
Seo-Hee Cho, Ji Yun Song, Jinyeon Shin, Seonhee Kim
BACKGROUND: Mutations of Crb1 gene cause irreversible and incurable visual impairment in humans. This study aims to use an LCA8-like mouse model to identify host-mediated responses that might interfere with survival, retinal integration and differentiation of grafted cells during neonatal cell therapy. METHODS: Mixed retinal donor cells (1 ~ 2 × 10(4)) isolated from neural retinas of neonatal eGFP transgenic mice were injected into the subretinal space of LCA8-like model neonatal mice...
November 4, 2016: BMC Ophthalmology
https://www.readbyqxmd.com/read/27701381/retinal-transplantation-of-photoreceptors-results-in-donor-host-cytoplasmic-exchange
#15
Tiago Santos-Ferreira, Sílvia Llonch, Oliver Borsch, Kai Postel, Jochen Haas, Marius Ader
Pre-clinical studies provided evidence for successful photoreceptor cell replacement therapy. Migration and integration of donor photoreceptors into the retina has been proposed as the underlying mechanism for restored visual function. Here we reveal that donor photoreceptors do not structurally integrate into the retinal tissue but instead reside between the photoreceptor layer and the retinal pigment epithelium, the so-called sub-retinal space, and exchange intracellular material with host photoreceptors...
October 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27701378/donor-and-host-photoreceptors-engage-in-material-transfer-following-transplantation-of-post-mitotic-photoreceptor-precursors
#16
R A Pearson, A Gonzalez-Cordero, E L West, J R Ribeiro, N Aghaizu, D Goh, R D Sampson, A Georgiadis, P V Waldron, Y Duran, A Naeem, M Kloc, E Cristante, K Kruczek, K Warre-Cornish, J C Sowden, A J Smith, R R Ali
Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors...
October 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27693410/an-important-role-for-adenine-cholera-toxin-hydrocortisone-and-triiodothyronine-in-the-proliferation-self-renewal-and-differentiation-of-limbal-stem-cells-in%C3%A2-vitro
#17
Min Yu, Sanja Bojic, Gustavo S Figueiredo, Paul Rooney, Julian de Havilland, Anne Dickinson, Francisco C Figueiredo, Majlinda Lako
The cornea is a self-renewing tissue located at the front of the eye. Its transparency is essential for allowing light to focus onto the retina for visual perception. The continuous renewal of corneal epithelium is supported by limbal stem cells (LSCs) which are located in the border region between conjunctiva and cornea known as the limbus. Ex vivo expansion of LSCs has been successfully applied in the last two decades to treat patients with limbal stem cell deficiency (LSCD). Various methods have been used for their expansion, yet the most widely used culture media contains a number of ingredients derived from animal sources which may compromise the safety profile of human LSC transplantation...
November 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27664291/gene-therapy-and-stem-cell-transplantation-in-retinal-disease-the-new-frontier
#18
Robert E MacLaren, Jean Bennett, Steven D Schwartz
Gene and cell therapies have the potential to prevent, halt, or reverse diseases of the retina in patients with currently incurable blinding conditions. Over the past 2 decades, major advances in our understanding of the pathobiologic basis of retinal diseases, coupled with growth of gene transfer and cell transplantation biotechnologies, have created optimism that previously blinding retinal conditions may be treatable. It is now possible to deliver cloned genes safely and stably to specific retinal cell types in humans...
October 2016: Ophthalmology
https://www.readbyqxmd.com/read/27644974/quantitative-metabolomics-of-photoreceptor-degeneration-and-the-effects-of-stem-cell-derived-retinal-pigment-epithelium-transplantation
#19
Junhua Wang, Peter D Westenskow, Mingliang Fang, Martin Friedlander, Gary Siuzdak
Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic 'fingerprint' of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques...
October 28, 2016: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/27641649/successful-transplantation-of-retinal-pigment-epithelial-cells-from-mhc-homozygote-ipscs-in-mhc-matched-models
#20
Sunao Sugita, Yuko Iwasaki, Kenichi Makabe, Hiroyuki Kamao, Michiko Mandai, Takashi Shiina, Kazumasa Ogasawara, Yasuhiko Hirami, Yasuo Kurimoto, Masayo Takahashi
There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models...
October 11, 2016: Stem Cell Reports
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