Embryonic stem cell trials for macular degeneration: a preliminary report

Schwartz, Steven D.; Hubschman, Jean‐Pierre; Heilwell, Gad; Franco-Cardenas, Valentina; Pan, Carolyn K.; Ostrick, Rosaleen; Mickunas, Edmund; Klimanskaya, Irina; Lanza, Robert

doi:10.1016/s0140-6736(12)60028-2

Cited by 1,279 publications

(1,008 citation statements)

References 29 publications

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“…The former were first established in 1998, 1 and their differentiated derivatives are now in clinical trials for allogeneic cell replacement therapy. 2,3 iPSCs are generated by somatic cell reprogramming and, despite minor differences, are quite similar to ESCs in their functional and molecular properties. [4][5][6][7][8] Because they are patient-specific, iPSC lines can be used in a wide range of biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

et al. 2016

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Kiselev (2016) An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion, Cell Cycle, 15:7, 986-997, DOI: 10.1080/15384101.2016 ABSTRACTThe pluripotency of newly developed human induced pluripotent stem cells (iPSCs) is usually characterized by physiological parameters; i.e., by their ability to maintain the undifferentiated state and to differentiate into derivatives of the 3 germ layers. Nevertheless, a molecular comparison of physiologically normal iPSCs to the "gold standard" of pluripotency, embryonic stem cells (ESCs), often reveals a set of genes with different expression and/or methylation patterns in iPSCs and ESCs. To evaluate the contribution of the reprogramming process, parental cell type, and fortuity in the signature of human iPSCs, we developed a complete isogenic reprogramming system. We performed a genome-wide comparison of the transcriptome and the methylome of human isogenic ESCs, 3 types of ESC-derived somatic cells (fibroblasts, retinal pigment epithelium and neural cells), and 3 pairs of iPSC lines derived from these somatic cells. Our analysis revealed a high input of stochasticity in the iPSC signature that does not retain specific traces of the parental cell type and reprogramming process. We showed that 5 iPSC clones are sufficient to find with 95% confidence at least one iPSC clone indistinguishable from their hypothetical isogenic ESC line. Additionally, on the basis of a small set of genes that are characteristic of all iPSC lines and isogenic ESCs, we formulated an approach of "the best iPSC line" selection and confirmed it on an independent dataset.

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Section: Introductionmentioning

confidence: 99%

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

et al. 2016

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“…The first use of hESC-derived RPE cells in human patients was described by Schwartz et al, in one patient with Stargardt's macular dystrophy and another with dry AMD. 63 Initial results show no significant improvement in visual function, but do suggest a good safety profile. The use of hESC for RPE transplantation not only entails ethical obstacles, but also carries a risk of immune rejection, especially, as surgical trauma is likely to compromise the blood retinal barrier and the immune privilege status of the subretinal space.…”

Section: Pluripotent Stem Cellsmentioning

confidence: 98%

Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

Alexander

Thomson

Luff

et al. 2015

Eye

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The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.

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“…(Trichonas et al 2010;Wong et al 2010;Zhang et al 2011a;Miller 2013;Tsai 2013). Subretinal transplantation of stem cells is also being investigated as a means of regenerating RPE cells and eventually, perhaps photoreceptors as well (Schwartz et al 2012).…”

Section: Treatments In Developmentmentioning

confidence: 99%

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

Yonekawa

Kim

2014

Cold Spring Harbor Perspectives in Medicine

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Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies.

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Embryonic stem cell trials for macular degeneration: a preliminary report

Cited by 1,279 publications

References 29 publications

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

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