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      Stem Cell Therapy for Treatment of Ocular Disorders

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          Abstract

          Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

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          Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

          Steven D Schwartz, Carl Regillo, Byron L Lam … (2015)
          The Lancet, 385(9967), 509-516
          Article 0 comments Cited 443 times – based on 0 reviews     Review now
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            Embryonic stem cell trials for macular degeneration: a preliminary report.

            Steven D Schwartz, Jean-Pierre Hubschman, Gad Heilwell … (2012)
            It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients. We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration--the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993. Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28). The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue. Advanced Cell Technology. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Hematopoietic stem cell: self-renewal versus differentiation.

              Jun Seita, Irving L Weissman (2010)
              The mammalian blood system, containing more than 10 distinct mature cell types, stands on one specific cell type, hematopoietic stem cell (HSC). Within the system, only HSCs possess the ability of both multipotency and self-renewal. Multipotency is the ability to differentiate into all functional blood cells. Self-renewal is the ability to give rise to HSC itself without differentiation. Since mature blood cells (MBCs) are predominantly short-lived, HSCs continuously provide more differentiated progenitors while properly maintaining the HSC pool size throughout life by precisely balancing self-renewal and differentiation. Thus, understanding the mechanisms of self-renewal and differentiation of HSC has been a central issue. In this review, we focus on the hierarchical structure of the hematopoietic system, the current understanding of microenvironment and molecular cues regulating self-renewal and differentiation of adult HSCs, and the currently emerging systems approaches to understand HSC biology. © 2010 John Wiley & Sons, Inc.
              Article 0 comments Cited 298 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Stem Cells Int
                Journal ID (iso-abbrev): Stem Cells Int
                Journal ID (publisher-id): SCI
                Title: Stem Cells International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-966X
                ISSN (Electronic): 1687-9678
                Publication date (Print): 2016
                Publication date (Electronic): 15 May 2016
                Volume: 2016
                Electronic Location Identifier: 8304879
                Affiliations
                1Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor, Malaysia
                2Department of Basic Medical Science and Department of Surgical Sciences, Ajman University of Science and Technology-Fujairah Campus, Al Fujairah, UAE
                3Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor, Malaysia
                4Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor, Malaysia
                5Department of Chemical and Materials Engineering, National Central University, Jhong-li, Taoyuan 32001, Taiwan
                6Department of Botany and Microbiology, King Saud University, Riyadh 11451, Saudi Arabia
                7Department of Reproduction, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
                8Division of Entomology, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India
                9Department of Zoology, Thiruvalluvar University, Serkkadu, Vellore 632 115, India
                Author notes
                *Akon Higuchi: higuchi@ 123456ncu.edu.tw and

                Academic Editor: Gary E. Lyons

                Article
                DOI: 10.1155/2016/8304879
                PMC ID: 4884591
                PubMed ID: 27293447
                SO-VID: e43b511d-290e-4d6f-8303-ad0b456927e3
                Copyright © Copyright © 2016 Padma Priya Sivan et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 29 January 2016
                Date accepted : 10 April 2016
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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