Scaffolds and stem cells: delivery of cell transplants for retinal degenerations

Kador, Karl E.; Goldberg, Jeffrey L

doi:10.1586/eop.12.56

Cited by 49 publications

(46 citation statements)

References 73 publications

(68 reference statements)

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“…Evidence has shown that using a polymer scaffold could offer better manipulation of the extracellular environment and afford the most appropriate degree of cell attachment, differentiation, and maintenance of apposite function (Tomita et al, 2005;Kador and Goldberg, 2012;Kundu et al, 2014). Current ongoing preclinical trials are applying various types of scaffolds for monolayer stem cells transplantation.…”

Section: Tissue Engineeringmentioning

confidence: 99%

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

174

142

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Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.

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Section: Tissue Engineeringmentioning

confidence: 99%

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

174

142

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“…[12] However, RGC transplantation is inherently more difficult than photoreceptor transplantation, as it requires the transplanted cells to integrate dendritically with their amacrine or bipolar cell presynaptic partners in the inner plexiform layer, extend their axons radially through the retina to the optic nerve, grow down the optic nerve and find their appropriate targets in the brain. Previously, we investigated the use of both PLL-PEG hydrogels [26] and PLA electrospun scaffolds [27] to study RGC survival and neurite growth and as a potential cell delivery vehicle. Unlike hydrogels, PLA electrospun scaffolds allowed RGC axons to replicate the radial organization of native RGCs in the retina, but they did not promote the polarization or centripetally directed growth seen in the retina in vivo.…”

Section: Discussionmentioning

confidence: 99%

Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold

et al. 2014

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Cell transplantation therapies to treat diseases related to dysfunction of retinal ganglion cells (RGCs) are limited in part by an inability to navigate to the optic nerve head within the retina. During development, RGCs are guided by a series of neurotrophic factors and guidance cues; however, these factors and their receptors on the RGCs are developmentally regulated and often not expressed during adulthood. Netrin-1 is a guidance factor capable of guiding RGCs in culture and relevant to guiding RGC axons toward the optic nerve head in vivo. Here we immobilized Netrin-1 using UV-initiated crosslinking to form a gradient capable of guiding the axonal growth of RGCs on a radial electrospun scaffold. Netrin-gradient scaffolds promoted both the percentage of RGCs polarized with a single axon, and also the percentage of cells polarized toward the scaffold center, from 31% to 52%. Thus, an immobilized protein gradient on a radial electrospun scaffold increases RGC axon growth in a direction consistent with developmental optic nerve head guidance, and may prove beneficial for use in cell transplant therapies for the treatment of glaucoma and other optic neuropathies.

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“…Furthermore, we propose that a well-characterized 3D tissue-engineered retina will provide many advantages in cost, animal usage, and assay specificity for programs interested in gene or drug screening. Finally, it will be a major step forward in cell replacement therapies currently being studied, to develop a 3D neural tissue platform as a starting point to study tissue/organ replacement therapy for the eye or brain, enhancing our understanding of the basic mechanisms of neuronal integration in these approaches, rebuilding neural circuitry in vitro , and replacing whole circuits in vivo [29]. …”

Section: Discussionmentioning

confidence: 99%

A tunable synthetic hydrogel system for culture of retinal ganglion cells and amacrine cells

et al. 2013

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The central nervous system (CNS) consists of complex groups of individual cells that receive electrical, chemical, and physical signals from their local environment. Standard in vitro cell culture methods rely on two-dimensional (2D) substrates that poorly simulate in vivo neural architecture. Neural cells grown in three-dimensional (3D) culture systems may provide an opportunity to study more accurate representations of the in vivo environment than 2D cultures. Furthermore, each specific type of neuron depends on discrete compositions and physical properties of their local environment. Previously, we developed a library of hydrogels composed of poly(ethylene glycol) (PEG) and poly(L-lysine) (PLL) which exhibit a wide range of mechanical properties. Here, we identified specific scaffolds from this library that readily support the survival, migration and neurite outgrowth of purified retinal ganglion cells (RGCs) and amacrine cells (ACs). These data address important biological questions about the interaction of neurons with the physical and chemical properties of their local environment and provide further insight for engineering neural tissue for cell-replacement therapies following injury.

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Scaffolds and stem cells: delivery of cell transplants for retinal degenerations

Cited by 49 publications

References 73 publications

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Retinal ganglion cell polarization using immobilized guidance cues on a tissue-engineered scaffold

A tunable synthetic hydrogel system for culture of retinal ganglion cells and amacrine cells

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