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Retina, stem cells

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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
#1
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/28296613/autologous-induced-stem-cell-derived-retinal-cells-for-macular-degeneration
#2
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/28258388/smad7-deficiency-stimulates-m%C3%A3-ller-progenitor-cell-proliferation-during-the-development-of-the-mammalian-retina
#3
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/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
#4
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/28249091/subretinal-glial-membranes-in-eyes-with-geographic-atrophy
#5
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/28246397/relationship-between-somatic-mosaicism-of-pax6-mutation-and-variable-developmental-eye-abnormalities-an-analysis-of-crispr-genome-edited-mouse-embryos
#6
Akihiro Yasue, Hitomi Kono, Munenori Habuta, Tetsuya Bando, Keita Sato, Junji Inoue, Seiichi Oyadomari, Sumihare Noji, Eiji Tanaka, Hideyo Ohuchi
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system is a rapid gene-targeting technology that does not require embryonic stem cells. To demonstrate dosage effects of the Pax6 gene on eye formation, we generated Pax6-deficient mice with the CRISPR/Cas system. Eyes of founder embryos at embryonic day (E) 16.5 were examined and categorized according to macroscopic phenotype as class 1 (small eye with distinct pigmentation), class 2 (pigmentation without eye globes), or class 3 (no pigmentation and no eyes)...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28242480/bifacial-stem-cell-niches-in-fish-and-plants
#7
REVIEW
Dongbo Shi, Tinatini Tavhelidse, Thomas Thumberger, Joachim Wittbrodt, Thomas Greb
Embryonic development is key for determining the architecture and shape of multicellular bodies. However, most cells are produced postembryonically in, at least partly, differentiated organs. In this regard, organismal growth faces common challenges in coordinating expansion and function of body structures. Here we compare two examples for postembryonic growth processes from two different kingdoms of life to reveal common regulatory principles: lateral growth of plants and the enlargement of the fish retina...
February 24, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28223209/langmuir-schaefer-film-deposition-onto-honeycomb-porous-films-for-retinal-tissue-engineering
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28216299/hipsc-derived-retinal-ganglion-cells-grow-dendritic-arbors-and-functional-axons-on-a-tissue-engineered-scaffold
#11
Kangjun Li, Xiufeng Zhong, Sijing Yang, Ziming Luo, Kang Li, Ying Liu, Song Cai, Huaiyu Gu, Shoutao Lu, Haijun Zhang, Yantao Wei, Jing Zhuang, Yehong Zhuo, Zhigang Fan, Jian Ge
Numerous therapeutic procedures in modern medical research rely on the use of tissue engineering for the treatment of retinal diseases. However, the cell source and the transplantation method are still a limitation. Previously, we reported on the induction of a self-organizing three-dimensional neural retina from human-induced pluripotent stem cells (hiPSCs). In this study, we disclose the generation of retinal ganglion cells (RGCs) from the neural retina and their seeding on a biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffold to create an engineered RGC-scaffold biomaterial...
February 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#12
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28210901/transplantation-of-lineage-negative-stem-cells-in-pterygopalatine-artery-ligation-induced-retinal-ischemia-reperfusion-injury-in-mice
#13
Gillipsie Minhas, Sudesh Prabhakar, Ryuichi Morishita, Munehisa Shimamura, Reema Bansal, Akshay Anand
Retinal ischemia is a condition associated with retinal degenerative diseases such as glaucoma, diabetic retinopathy, and other optic neuropathies, leading to visual impairment and blindness worldwide. Currently, there is no therapy available for ischemic retinopathies. Therefore, the aim of this study was to test a murine model of pterygopalatine artery ligation-induced retinal injury for transplantation of mouse bone marrow-derived lineage-negative (lin-ve) stem cells. The mouse external carotid artery and pterygopalatine artery were ligated for 3...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28205557/experimental-study-of-the-biological-properties-of-human-embryonic-stem-cell-derived-retinal-progenitor-cells
#14
Jingzhi Shao, Peng-Yi Zhou, Guang-Hua Peng
Retinal degenerative diseases are among the leading causes of blindness worldwide, and cell replacement is considered as a promising therapeutic. However, the resources of seed cells are scarce. To further explore this type of therapy, we adopted a culture system that could harvest a substantial quantity of retinal progenitor cells (RPCs) from human embryonic stem cells (hESCs) within a relatively short period of time. Furthermore, we transplanted these RPCs into the subretinal spaces of Royal College of Surgeons (RCS) rats...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202390/systemic-injection-of-rpe65-programmed-bone-marrow-derived-cells-prevents-progression-of-chronic-retinal-degeneration
#15
Xiaoping Qi, S Louise Pay, Yuanqing Yan, James Thomas, Alfred S Lewin, Lung-Ji Chang, Maria B Grant, Michael E Boulton
Bone marrow stem and progenitor cells can differentiate into a range of non-hematopoietic cell types, including retinal pigment epithelium (RPE)-like cells. In this study, we programmed bone marrow-derived cells (BMDCs) ex vivo by inserting a stable RPE65 transgene using a lentiviral vector. We tested the efficacy of systemically administered RPE65-programmed BMDCs to prevent visual loss in the superoxide dismutase 2 knockdown (Sod2 KD) mouse model of age-related macular degeneration. Here, we present evidence that these RPE65-programmed BMDCs are recruited to the subretinal space, where they repopulate the RPE layer, preserve the photoreceptor layer, retain the thickness of the neural retina, reduce lipofuscin granule formation, and suppress microgliosis...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28194183/regulation-of-stem-cell-properties-of-m%C3%A3-ller-glia-by-jak-stat-and-mapk-signaling-in-the-mammalian-retina
#16
REVIEW
Krista M Beach, Jianbo Wang, Deborah C Otteson
In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28192065/vascular-endothelial-growth-factor-a-and-leptin-expression-associated-with-ectopic-proliferation-and-retinal-dysplasia-in-zebrafish-optic-pathway-tumors
#17
Laura E Schultz, Staci L Solin, Wesley A Wierson, Janna M Lovan, Judith Syrkin-Nikolau, Deborah E Lincow, Andrew J Severin, Donald S Sakaguchi, Maura McGrail
In the central nervous system injury induces cellular reprogramming and progenitor proliferation, but the molecular mechanisms that limit regeneration and prevent tumorigenesis are not completely understood. We previously described a zebrafish optic pathway tumor model in which transgenic Tg(flk1:RFP)is18/+ adults develop nonmalignant retinal tumors. Key pathways driving injury-induced glial reprogramming and regeneration contributed to tumor formation. In this study, we examine a time course of proliferation and present new analyses of the Tg(flk1:RFP)is18/+ dysplastic retina and tumor transcriptomes...
February 13, 2017: Zebrafish
https://www.readbyqxmd.com/read/28191500/insights-from-genetic-model-systems-of-retinal-degeneration-role-of-epsins-in-retinal-angiogenesis-and-vegfr2-signaling
#18
Yunzhou Dong, Xue Cai, Yong Wu, Yanjun Liu, Lin Deng, Hong Chen
The retina is a light sensitive tissue that contains specialized photoreceptor cells called rods and cones which process visual signals. These signals are relayed to the brain through interneurons and the fibers of the optic nerve. The retina is susceptible to a variety of degenerative diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP) and other inherited retinal degenerations. In order to reveal the mechanism underlying these diseases and to find methods for the prevention/treatment of retinal degeneration, animal models have been generated to mimic human eye diseases...
January 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28164440/effect-of-human-umbilical-cord-blood-mesenchymal-stem-cells-administered-by-intravenous-or-intravitreal-routes-on-cryo-induced-retinal-injury
#19
Eman M Mohamed, Shaimaa A Abdelrahman, Samia Hussein, Sally M Shalaby, Hala Mosaad, Ahmed M B Awad
Traumatic optic neuropathy is an important cause of severe vision loss. So, many attempts were performed to transplant stem cells systemically or locally to regenerate the injured retina. In this study, we investigated the effect of human umbilical cord blood mesenchymal stem cells (hUBMSCs) on histological structure, apoptotic, antiapoptotic, oxidant and antioxidant markers in an experimental model of cryo-induced retinal damage in mice. Forty-eight mice were included with 4 major groups; group I contained 18 mice as controls...
February 5, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28162200/-the-protective-effect-of-human-umbilical-cord-mesenchymal-stem-cells-induced-neural-stem-cells-in-the-vitreous-on-the-blood-retinal-barrier-in-diabetic-rats
#20
M Dong, W Zhang, S Chen, J M Wang, H T Duan, J H Kong, Y X Wang, X Bi, J Song
Objective: To investigate the effect of intravitreal injection of neural stem cells (NSC) induced from human umbilical cord mesenchymal stem cells, and to provide a theoretical basis for the clinical treatment of blood-retinal barrier damage due to diabetic retinopathy (DR). Methods: Experimental study. Sixty male Sprague-Dawley rats were randomly divided into control group, DR group and NSC group. Diabetic rats were induced by injection of streptozotocin, and the control rats were injected with an equal volume of solvent...
January 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
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