ARPE-19, A Human Retinal Pigment Epithelial Cell Line with Differentiated Properties

Dunn, K. C.; Aotaki-Keen, A. E.; Putkey, Frances R.; Hjelmeland, Leonard M.

doi:10.1006/exer.1996.0020

Cited by 1,141 publications

(1,014 citation statements)

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“…This fragment was inserted between the BglII and EcoRV sites in the SB substrate vector pT2BH to create the pT2.CAn.hNGF plasmid. The ARPE-19 cell line 16 was cultured and transfected as previously described. 15 Cells were co-transfected with plasmids pT2.CAn.hNGF and pCMV-SB-100X with the hyperactive version of the SB transposase (both the SB substrate vector pT2BH and the hyperactive SB transposase were kind gifts from Drs Zsuzsanna Izsvak and Zoltan Ivics, MDC, Berlin, Germany).…”

Section: Establishment Of the Ngf-expressing Ngc0211 Cell Linementioning

confidence: 99%

“…15 The clinical product, named NsG0202, contains NGF-secreting NGC-0295 cells, derived from a human retinal pigment epithelial (RPE) cell line, ARPE-19. This spontaneously immortalised cell line shows contact-inhibited growth and survives well in nutrient-poor culture environments, 16 making it well suited for encapsulation. A small phase 1b clinical study to examine the safety of NsG0202 devices implanted in the basal forebrain of patients with mild to moderate AD has shown promising results (Eriksdotter-Jö nhagen et al; Wahlberg et al, manuscripts submitted).…”

Section: Introductionmentioning

confidence: 99%

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Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer

et al. 2011

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Nerve growth factor (NGF) is a potential therapeutic agent for Alzheimer's disease (AD) as it has positive effects on the basal forebrain cholinergic neurons whose degeneration correlates with the cognitive decline in AD. We have previously described an encapsulated cell biodelivery device, NsG0202, capable of local delivery of NGF by a genetically modified human cell line, NGC-0295. The NsG0202 devices have shown promising safety and therapeutic results in a small phase 1b clinical study. However, results also show that the NGF dose could advantageously be increased. We have used the sleeping beauty transposon expression technology to establish a new clinical grade cell line, NGC0211, with at least 10 times higher NGF production than that of NGC-0295. To test whether encapsulation of this cell line provides a relevant dose escalation step in delivering NGF for treatment of the cognitive decline in AD patients, we have validated the bioactivity of devices with NGC0211 and NGC-0295 cells in normal rat striatum as well as in the quinolinic acid striatal lesion model. These preclinical animal studies show that implantation of devices with NGC0211 cells lead to significantly higher NGF output, which in both cases correlate with highly improved potency.

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Section: Establishment Of the Ngf-expressing Ngc0211 Cell Linementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer

et al. 2011

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“…The adult retinal pigmented epithelium cell line, ARPE-19, was purchased from American Type Culture Collection (ATCC, Rockville, MD) and cultured as described by Dunn et al [1996] except they were revived in 5.5 mM instead of 18 mM glucose and were grown in 5% CO 2 instead of 10%. ARPE-19 cells were grown to confluence in T-75 flasks (~3-5 days) in Dulbecco's Modified Eagle Medium/F12-Nutrient Mixture (DMEM, Gibco; F-12 Nutrient Mixture, Gibco; obtained without glucose and then supplemented by adding glucose to the appropriate concentrations) with 15 mM HEPES buffer (Gibco), 10% fetal bovine serum (Gibco), 5.5 mM glucose, 0.35% additional sodium bicarbonate, 2.5 mM Lglutamine, and 1% penicillin/streptomycin at 37°C.…”

Section: Arpe-19 Cell Culturementioning

confidence: 99%

“…Media was changed every other day. At confluence, these cells are undifferentiated (i.e., without melanin) but express several visual proteins [Dunn et al, 1996] including the LRAT enzyme [Trevino et al, 2005].…”

Section: Arpe-19 Cell Culturementioning

confidence: 99%

“…suggesting that they are appropriate for in-vitro studies of RPE functions [Dunn et al, 1996]. ARPE-19 cells have also been shown to release vascular endothelial growth factor (VEGF) in response to amino acid deprivation (metabolic stress; [Abcouwer et al, 2002]), 4-hydroxynonenal (oxidative stress; [Ayalasomayajula and Kompella, 2002]), and SA3443, a synthetic cyclic disulfide compound (anti-inflammation; [Muranaka et al, 2005]).…”

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confidence: 99%

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Bone morphogenetic protein‐4 enhances vascular endothelial growth factor secretion by human retinal pigment epithelial cells

Vogt

Unda

Yeh

et al. 2006

J of Cellular Biochemistry

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Retinal pigment epithelial (RPE) cells secrete vascular endothelial growth factor (VEGF), a cytokine known to promote angiogenesis. Results from RNase protection assays (RPAs) show that RPE from non-diabetic human donors and from adult retinal pigment epithelium-19 (ARPE-19) cells expressed significant bone morphogenetic protein-4 (BMP-4) message. In addition, ARPE-19 cells cultured in high glucose (25 mM), compared to those in physiological glucose (5.5 mM) released significantly more BMP-4 into the conditioned media (CM). However, the effect of BMP-4 on the release of VEGF by ARPE-19 cells has not been studied. Accordingly, ARPE-19 cells were treated with BMP-4 to determine VEGF secretion. BMP-4 and VEGF levels in the CM and cell lysates were measured by enzyme-linked immunosorbent assay (ELISA). Cells treated with exogenous BMP-4 had higher VEGF in the CM and this treatment effect was dose-and timedependent, while cell lysates had low levels of VEGF. Addition of cycloheximide (CHX) or actinomycin-D (ACT) significantly reduced VEGF secretion from cells treated with BMP-4, suggesting that the BMP-4-induced secretion of VEGF requires new RNA and protein synthesis. Our results suggest that BMP-4 may play a role in the regulation of ocular angiogenesis associated with diabetic retinopathy (DR) by stimulating VEGF release from RPE cells.

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Cytotoxicity of Indocyanine Green on Retinal Pigment Epithelium

Ho¹

2003

Arch Ophthalmol

114

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To evaluate the potential cytotoxic effects of indocyanine green (ICG) on cultured human retinal pigment epithelium (RPE) and the resultant implications for macular hole surgery.Methods: Human RPE cells were exposed to ICG in concentrations from 0.001 to 5 mg/mL. The exposure duration ranged from 5 minutes to 3 hours. Light microscopy, MTS viability assay, and calcein AM-ethidium homodimer 1 staining were used to evaluate the cytotoxic effects of ICG. Results:The RPE cells incubated with up to 5 mg/mL of ICG for 5 minutes or less exhibited no morphologic change and no significant decrease in dehydrogenase activity. When RPE cells were exposed to 5 mg/mL of ICG for 10 minutes, 1 mg/mL of ICG for 20 minutes, or 0.01 mg/mL of ICG for 3 hours, cell morphologic features were altered, mitochondrial dehydrogenase activity decreased, and some cells were necrotic.

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ARPE-19, A Human Retinal Pigment Epithelial Cell Line with Differentiated Properties

Cited by 1,141 publications

References 0 publications

Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer

Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer

Bone morphogenetic protein‐4 enhances vascular endothelial growth factor secretion by human retinal pigment epithelial cells

Cytotoxicity of Indocyanine Green on Retinal Pigment Epithelium

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