Early Attachment of Uncultured Retinal Pigment Epithelium from Aged Donors onto Bruch's Membrane Explants

Tsukahara, Itsuro; Ninomiya, Satoko; Castellarin, Alessandro; Yagi, Fumihiko; Sugino, Ilene K.; Zarbin, Marco A.

doi:10.1006/exer.2001.1123

Cited by 54 publications

(33 citation statements)

References 63 publications

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“…Transplantation of RPE sheets was found to be more suitable than injection of RPE cell suspensions, as assembled cells may already carry spatial information [Kubota et al, 2006]. Recent studies have revealed that although uncultured aged adult RPE cells are not suitable for resurfacing Bruch's membrane [Tsukahara et al, 2002], resurfacing is possible with cultured fetal and adult RPE cells [Castellarin et al, 1998;Zarbin, 2003]. Moreover, in vitro cultivation induces upregulation of ␣ 1-5 integrin subunit production in RPE cells, which facilitates successful cell attachment and spreading on Bruch's membrane [Imai et al, 2007;Gullapalli et al, 2008].…”

Section: Introductionmentioning

confidence: 99%

Retinal Pigment Epithelium Cell Alignment on Nanostructured Collagen Matrices

Ulbrich¹,

Friedrichs²,

Valtink³

et al. 2011

Cells Tissues Organs

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We investigated attachment and migration of human retinal pigment epithelial cells (primary, SV40-transfected and ARPE-19) on nanoscopically defined, two-dimensional matrices composed of parallel-aligned collagen type I fibrils. These matrices were used non-cross-linked (native) or after riboflavin/UV-A cross-linking to study cell attachment and migration by time-lapse video microscopy. Expression of collagen type I and IV, MMP-2 and of the collagen-binding integrin subunit α₂ were examined by immunofluorescence and Western blotting. SV40-RPE cells quickly attached to the nanostructured collagen matrices and aligned along the collagen fibrils. However, they disrupted both native and cross-linked collagen matrices within 5 h. Primary RPE cells aligned more slowly without destroying either native or cross-linked substrates. Compared to primary RPE cells, ARPE-19 cells showed reduced alignment but partially disrupted the matrices within 20 h after seeding. Expression of the collagen type I-binding integrin subunit α₂ was highest in SV40-RPE cells, lower in primary RPE cells and almost undetectable in ARPE-19 cells. Thus, integrin α₂ expression levels directly correlated with the degree of cell alignment in all examined RPE cell types. Specific integrin subunit α₂-mediated matrix binding was verified by preincubation with an α₂-function-blocking antibody, which impaired cell adhesion and alignment to varying degrees in primary and SV40-RPE cells. Since native matrices supported extended and directed primary RPE cell growth, optimizing the matrix production procedure may in the future yield nanostructured collagen matrices serving as transferable cell sheet carriers.

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Section: Introductionmentioning

confidence: 99%

Retinal Pigment Epithelium Cell Alignment on Nanostructured Collagen Matrices

Ulbrich¹,

Friedrichs²,

Valtink³

et al. 2011

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…Sources of RPE cells that have been used in these procedures include rotated pedicled flaps of peripheral RPE-choroid, autologous free RPE-choroid grafts, sheets of foetal RPE and cell suspensions of peripheral RPE (Binder et al, 2007;da Cruz et al, 2007;Chen et al, 2009;van Zeeburg et al, 2012). In the last approach, one of the major drawbacks is that there is no guarantee that the cells in suspension can first attach to the diseased Bruch's membrane (Tsukahara et al, 2002). Moreover, those cells that attach often do not form the desired monolayer that is required for optimal RPE function, and they instead clump into rosettes (Vugler et al, 2008) or undergo anoikis (Tezel et al, 2004), a form of apoptosis specific to anchorage-dependent cells that are dissociated from their usual extracellular matrix.…”

Section: Retinal Transplantation In Amd: Proof Of Principlementioning

confidence: 99%

Stem cells in retinal regeneration: past, present and future

et al. 2013

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SummaryStem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

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“…Tsukahara et al using ex vivo models of aged Bruch's membrane have shown that the resurfacing of the Bruch's membrane is highly dependent on whether the basement membrane is intact or removed. The adhesion of RPE cells was much higher on aged Bruch's membrane if the basement membrane was not damaged and removed (Tsukahara et al, 2002). Therefore, one of the limitations of the CNV removal procedure is the iatrogenic removal of the laminin rich basement membrane, which reduces the chance of adhesion of RPE cells transplanted subsequently into the subretinal space.…”

Section: Surgical and Cellular Transplantation/replacementmentioning

confidence: 99%

Wet Age-Related Macular Degeneration

García-Aguirre¹

2016

Ophthalmology: Current and Future Developments

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Early Attachment of Uncultured Retinal Pigment Epithelium from Aged Donors onto Bruch's Membrane Explants

Cited by 54 publications

References 63 publications

Retinal Pigment Epithelium Cell Alignment on Nanostructured Collagen Matrices

Retinal Pigment Epithelium Cell Alignment on Nanostructured Collagen Matrices

Stem cells in retinal regeneration: past, present and future

Wet Age-Related Macular Degeneration

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