Human Embryonic Stem Cell–Derived Cells Rescue Visual Function in Dystrophic RCS Rats

Lund, Raymond D.; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lü, Bin; Girman, Sergey; Bischoff, Nicholas; Sauvé, Yves; Lanza, Robert

doi:10.1089/clo.2006.8.189

Cited by 381 publications

(291 citation statements)

References 31 publications

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“…When transplanted into the retina, ESC-derived NSCs show limited incorporation and differentiation into photoreceptor cell fates. Importantly, functional rescue of the outer retina in an animal model is observed after transplantation of ESC-NSCs [48][49][50]. Teratomas were not observed after transplantation of ESC-NSCs, although tumors were observed with related neurally selected ESCs [51].…”

Section: Neural Stem Cellsmentioning

confidence: 97%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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Retinal degenerative disease has limited therapeutic options and the possibility of stem cell-mediated regenerative treatments is being actively explored for these blinding retinal conditions. The relative accessibility of this central nervous system tissue and the ability to visually monitor changes after transplantation make the retina and adjacent retinal pigment epithelium prime targets for pioneering stem cell therapeutics. Prior work conducted for several decades indicated the promise of cell transplantation for retinal disease, and new strategies that combine these established surgical approaches with stem cell-derived donor cells is ongoing. A variety of tissue-specific and pluripotent-derived donor cells are being advanced to replace lost or damaged retinal cells and/or to slow the disease processes by providing neuroprotective factors, with the ultimate aim of long-term improvement in visual function. Clinical trials are in the early stages, and data on safety and efficacy are widely anticipated. Positive outcomes from these stem cell-based clinical studies would radically change the way that blinding disorders are approached in the clinic.

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Section: Neural Stem Cellsmentioning

confidence: 97%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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“…Human RPE derived from hESCs (hESC-RPE) was generated using published protocols 23,24 Briefly, the hESC line WA09 (WiCell Research Institute) 25 was allowed to spontaneously mature in standard hESC media (7-10 days). The medium was then changed to differentiation media, which consisted of knockout DMEM (koDMEM), 15% knockout serum replacer (KOSR), 1% l-glutamine, 1% penicillin/ streptomycin solution, 1% NEAA, and 0.1 mM b-mercaptoethanol (b-ME; Sigma).…”

Section: Rpe Cell Linesmentioning

confidence: 99%

Enhanced Functional Integration of Human Photoreceptor Precursors into Human and Rodent Retina in anEx VivoRetinal Explant Model System

Yanai

Laver

Gregory‐Evans

et al. 2015

Tissue Engineering Part A

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Retinal disease is the major cause of irreversible blindness in developed countries. Transplantation of photoreceptor precursor cells (PPCs) derived from human embryonic stem cells (hESCs) is a promising and widely applicable approach for the treatment of these blinding conditions. Previously, it has been shown that after transplantation into the degenerating retina, the percentage of PPCs that undergo functional integration is low. The factors that inhibit PPC engraftment remain largely unknown, in part, because so many adverse factors could be at play during in vivo experiments. To advance our knowledge in overcoming potential adverse effects and optimize PPC transplantation, we have developed a novel ex vivo system. Harvested neural retina was placed directly on top of cultured retinal pigment epithelial (RPE) cells from a number of different sources. To mimic PPC transplantation into the subretinal space, hESC-derived PPCs were inserted between the retinal explant and underlying RPE. Explants cocultured with hESC-derived RPE maintained normal gross morphology and viability for up to 2 weeks, whereas the explants cultured on ARPE19 and RPE-J failed by 7 days. Furthermore, the proportion of PPCs expressing ribbon synapse-specific proteins BASSOON and RIBEYE was significantly higher when cocultured with hESC-derived RPE (20% and 10%, respectively), than when cocultured with ARPE19 (only 6% and 2%, respectively). In the presence of the synaptogenic factor thrombospondin-1 (TSP-1), the proportion of BASSOON-positive and RIBEYE-positive PPCs cocultured with hESC-derived RPE increased to *30% and 15%, respectively. These data demonstrate the utility of an ex vivo model system to define factors, such as TSP-1, which could influence integration efficiency in future in vivo experiments in models of retinal degeneration.

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“…Identifying ethical and clinically available sources for cells will require careful consideration. Although embryonic-and foetalderived stem cells have shown the capacity to generate retinal-like neurons [24][25][26][27][28] and confer retinal neuroprotection, 12,29 ethical and logistic issues, including graft rejection resulting from inherent allogenic transplantation, will likely restrict their clinical utility. Various types of stem/progenitor cells exist in the adult mammalian body, including the eye, [30][31][32][33] and further research into using these cells for transplantation is of interest.…”

Section: Future Directionsmentioning

confidence: 99%

Transplantation prospects for the inner retina

Johnson

Bull

Martin

2008

Eye

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Transplantation of stem or progenitor cells is an attractive new approach for treating neurodegenerative conditions of the central nervous system, which aims to protect or replace neurons and improve function. Proof of principle has already been shown in the retina that photoreceptors may be replaced by transplantation of neural progenitor cells. However, the task of retinal ganglion cell replacement is much more complex, as new cells will need to establish complex connections within the retina and also extend axons to precise targets in the brain. Although progress has been made in this field, it is likely that neuroprotective clinical applications will be established more quickly. Our laboratory has focused on the intraocular transplantation of cells to treat inner retinal disease, either by neuronal replacement or neuroprotection of existing cells. We have investigated the efficacy and effects of transplanting a variety of cell types, including human Mü ller stem cells (MIO-M1), oligodendrocyte precursor cells (OPCs), and bone marrow-derived mesenchymal stromal cells (MSCs) in a rat model of experimentally induced glaucoma. We also have developed and characterized a novel in vitro organotypic retinal explant culture system for exploring the methods of enhancing the efficacy of cell transplantation for the inner retina. In this review, we discuss the potentially beneficial effects of intraocular cell injections, identify current shortcomings of retinal stem cell therapy, and suggest directions for future research.

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Human Embryonic Stem Cell–Derived Cells Rescue Visual Function in Dystrophic RCS Rats

Cited by 381 publications

References 31 publications

Stem Cells for Retinal Replacement Therapy

Stem Cells for Retinal Replacement Therapy

Enhanced Functional Integration of Human Photoreceptor Precursors into Human and Rodent Retina in anEx VivoRetinal Explant Model System

Transplantation prospects for the inner retina

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