Human RPE Stem Cells Grown into Polarized RPE Monolayers on a Polyester Matrix Are Maintained after Grafting into Rabbit Subretinal Space

Stanzel, Boris V.; Liu, Zengping; Somboonthanakij, Sudawadee; Wongsawad, Warapat; Brinken, Ralf; Eter, Nicole; Corneo, Barbara; Holz, Frank G.; Temple, Sally; Stern, Jeffrey H.; Blenkinsop, Timothy A.

doi:10.1016/j.stemcr.2013.11.005

Cited by 147 publications

(138 citation statements)

References 44 publications

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“…There have been reports that suspension-injected RPE are more sensitive to immune rejection compared with monolayer transplantation [31]. This is thought to be attributed to the disruption of the monolayer [32,33]. Third, dissociated RPE cells are more sensitive to oxidative stress-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Polarized Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cell Monolayers Have Higher Resistance to Oxidative Stress-Induced Cell Death Than Nonpolarized Cultures

Hsiung

Zhu

Hinton

2014

Stem Cells Translational Medicine

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Oxidative stress-mediated injury to the retinal pigment epithelium (RPE) is a major factor involved in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. Human embryonic stem cell (hESC)-derived RPE cells are currently being evaluated for their potential for cell therapy in AMD patients through subretinal injection of cells in suspension and subretinal placement as a polarized monolayer. To gain an understanding of how transplanted RPE cells will respond to the highly oxidatively stressed environment of an AMD patient eye, we compared the survival of polarized and nonpolarized RPE cultures following oxidative stress treatment. Polarized, nonpolarized/confluent, nonpolarized/subconfluent hESC-RPE cells were treated with H 2 O 2 . Terminal deoxynucleotidyl transferase dUTP nick end labeling stains revealed the highest amount of cell death in subconfluent hESC-RPE cells and little cell death in polarized hESC-RPE cells with H 2 O 2 treatment. There were higher levels of proapoptotic factors (phosphorylated p38, phosphorylated c-Jun NH 2 -terminal kinase, Bax, and cleaved caspase 3 fragments) in treated nonpolarized RPE-particularly subconfluent cells-relative to polarized cells. On the other hand, polarized RPE cells had constitutively higher levels of cell survival and antiapoptotic signaling factors such as p-Akt and Bcl-2, as well as antioxidants superoxide dismutase 1 and catalase relative to nonpolarized cells, that possibly contributed to polarized cells' higher tolerance to oxidative stress compared with nonpolarized RPE cells. Subconfluent cells were particularly sensitive to oxidative stress-induced apoptosis. These results suggest that implantation of polarized hESC-RPE monolayers for treating AMD patients with geographic atrophy should have better survival than injections of hESC-RPE cells in suspension. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:10-20

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Section: Discussionmentioning

confidence: 99%

Polarized Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cell Monolayers Have Higher Resistance to Oxidative Stress-Induced Cell Death Than Nonpolarized Cultures

Hsiung

Zhu

Hinton

2014

Stem Cells Translational Medicine

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“…Photoreceptor degeneration is difficult to treat because the pathological process involves the apoptosis of photoreceptors or RPE cells, and photoreceptor cells cannot regenerate or self-repair. Although RPE cells have the capacity to proliferate in vivo and in vitro (Chiba, 2014;Stanzel et al, 2014), it is difficult for damaged RPE cells to repair themselves (Chiba, 2014). Currently, there are several treatment methods available, including gene therapy, transplantation therapy, drug therapy and artificial vision prostheses.…”

Section: Introductionmentioning

confidence: 99%

c-Kit+ cells isolated from human fetal retinas represent a new population of retinal progenitor cells

Zhou

Peng

et al. 2015

Journal of Cell Science

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“…Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are used in transplantation therapies [50] . These cells are extensively used in retinal repair [51] .…”

Section: Stem Cell Therapiesmentioning

confidence: 99%

Cell Replacement Therapy for Optic Nerve Disorders

Upadhyay¹,

Internationals²

2017

JSRB

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This review article explains major optic nerve disorders and cell replacement therapy. This article also signifies new innovative methods, biopharmaceuticals, implantable biomaterials, devices and diagnostic tools developed for restoration of vision. It asserts notable technological advancements made for regeneration of neurons and restoration of visual system network. However, for finding quick solutions of optical-neuronal disorders more advanced biomaterial cell scaffolds and concurrent efforts are needed to revitalize visual-neural receptor system. This article stresses upon novel bioengineered methods mainly required to activate endogenous stem and progenitor cells, which could reawaken cells in dormancy, instructing them to promote repair and regeneration in optic nerve cells and retina. For better management of optic nerve disorders, important role of tissues, genes, growth factors and proteins, nano-medicine and nanotechnology, and all underlying mechanisms should fully investigated. This article tries to explore all possibilities to find quick solutions for treatment of loss of vision/ photoreceptors and degeneration of optic neural network despite all ongoing challenges. Moreover, for solving visual disorders, neurodegenerative blinding diseases novel cell-based therapeutic strategies are to be developed with future applications in regenerative medicine.

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Human RPE Stem Cells Grown into Polarized RPE Monolayers on a Polyester Matrix Are Maintained after Grafting into Rabbit Subretinal Space

Cited by 147 publications

References 44 publications

Polarized Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cell Monolayers Have Higher Resistance to Oxidative Stress-Induced Cell Death Than Nonpolarized Cultures

Polarized Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cell Monolayers Have Higher Resistance to Oxidative Stress-Induced Cell Death Than Nonpolarized Cultures

c-Kit+ cells isolated from human fetal retinas represent a new population of retinal progenitor cells

Cell Replacement Therapy for Optic Nerve Disorders

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