Experimental transplantation of human retinal pigment epithelial cells on collagen substrates

Bhatt, Nitul; Newsome, David A.; Diamond, James G.

doi:10.1007/978-94-011-5137-5_18

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…Furthermore, apical-basal polarity may need to be re-established by donor RPE for proper epithelial homeostasis. To this end, RPE-sheets grown on scaffolds with pre-established polarity showed greater retinal survival and function following transplant [27][28][29]; however, artificial implants risk further reducing the ONL nutrient supply and may elicit immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model

et al. 2015

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Pluripotent stem cell derived retinal pigment epithelial (RPE) cells are currently being tested for cell replacement in late-stage age-related macular degeneration (AMD). However, preserving vision at early-stages may also be possible. Here we demonstrate that transplantation of neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iNPCs) limits disease progression in the Royal College of Surgeons (RCS) rat, a preclinical model of AMD. Grafted-iNPCs survived, remained undifferentiated, and distributed extensively in a laminar fashion in the subretinal space. Retinal pathology resulting from the accumulation of undigested photoreceptor outer segments (POS) was significantly reduced in iNPC-injected rats compared with controls. Phagosomes within grafted-iNPCs contained POS, suggesting that iNPCs had compensated for defective POS phagocytosis by host-RPE. The iNPC-treated eyes contained 6–8 rows of photoreceptor nuclei that spanned up to 5 mm in length in transverse retinal sections, compared with only one row of photoreceptors in controls. iNPC treatment fully preserved visual acuity measured by optokinetic response. Electrophysiological recordings revealed that retina with the best iNPC-protected areas were 140-fold more sensitive to light stimulation than equivalent areas of contralateral eyes. The results described here support the therapeutic utility of iNPCs as autologous grafts for early-stage of AMD.

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Section: Discussionmentioning

confidence: 99%

Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model

et al. 2015

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“…It seems that transplantation in the form of a patch is important in preventing cell disorganization, excessive mechanical stress or damage of the well oriented cells and in facilitating precise localization of the graft. Several support matrices have been utilized in different studies (Bhatt et al 1994;Oganesani et al 1996;Thumann et al 1997;Lu et al 1998;Farrokh-Siar et al 1999;Hartmann et al 1999;Tezel & Del Priore 1999;Tsukahara et al 2002). Most of these supports turned out either to be toxic to the cells or to disintegrate on exposure to liquid media.…”

Section: Discussionmentioning

confidence: 99%

“…These include biological supports such as Descemet's membrane (Thumann et al 1997), lens capsule (Hartmann et al 1999), Bruch's membrane or blood cryoprecipitates (Farrokh-Siar et al 1999). Other groups have studied the application of synthetic supports, such as collagen substrates (Bhatt et al 1994), biodegradable polymer films (Lu et al 1998) or microspheres (Oganesani et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Amniotic membrane as support for human retinal pigment epithelium (RPE) cell growth

Capeáns

Piñeiro²,

Pardo³

et al. 2003

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: The aim of this work was to culture human retinal pigment epithelium (hRPE) cells over human amniotic membrane (hAM). Human AM was studied for its viability as an adequate support for transplantation of an hRPE cell monolayer with preserved cell polarity to the subretinal space. Methods: Human AM was obtained from pregnant women during caesarean section. The hAM was sectioned and the pieces were fixed to culture dishes. Human RPE cells were cultured from adult corneal donors and were seeded over hAM. Phase-contrast photographs were obtained. Selected specimens were processed by transmission electronic microscopy (TEM). Results: The attachment and growth of hRPE cells over hAM was observed. Human RPE cells constituted tight colonies that maintained epithelial phenotype. Using TEM, we identified a monolayer of hRPE cells, with cuboidal to spheroidal morphology. These cells showed integration with the substrate and cellÀcell contacts were detected. Conclusion: Amniotic membrane may be a suitable substrate for hRPE growth. Further studies are required in order to determine the viability of hRPE on hAM in the subretinal space.

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“…These scaffolds show positive results in vitro, successfully maintaining viable RPE cells capable of forming monolayers with tight junctions and phagocytic ability. [13][14][15][16][17] Despite these in vitro successes, there are still challenges that must be addressed upon implantation of cell-seeded scaffolds. First, a common occurrence following scaffold implantation is that the immune cells of the nervous system, the microglia, begin to appear in the neural retina and are accompanied by the formation of a microglial scar on the retinal side of the scaffold.…”

Section: Introductionmentioning

confidence: 99%

The influence of substrate modulus on retinal pigment epithelial cells

White

DiStefano

Olabisi

2017

J Biomedical Materials Res

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Although transplantation of retinal pigment epithelial (RPE) cells has shown promise for the treatment of retinal degenerative diseases, this therapeutic approach is not without challenges. Two major challenges are RPE cell dedifferentiation and inflammatory response following transplantation. The aim of this work is to understand how the rigidity of a scaffold, a relatively unexplored design aspect in retinal tissue engineering, affects RPE cells, particularly the pathways associated with the aforementioned challenges. Poly(ethylene glycol) diacrylate (PEGDA) of varying molecular weights from 3.4 to 20 kDa were photopolymerized to fabricate scaffolds. The Young's modulus of the scaffolds varied from 60 to 1200 kPa. A cell study was then conducted to test the effects of scaffold rigidity on RPE cells. A cell adhesion peptide motif of arginine-glycine-aspartic acid-serine (RGDS) was conjugated to 60 and 1200 kPa scaffolds and ARPE-19 cells, a human RPE cell line, were seeded onto these hydrogels. Cells grown on scaffolds demonstrated qualitatively different adhesion properties, metabolic activity, and gene expression at an mRNA level. IL-6 and MCP-1, two inflammation markers known to recruit microglial into the retina, had the same expression pattern with cells having the highest expression on the high modulus scaffold and lowest expression on the control substrate. This study demonstrates that scaffold rigidity, an important design parameter in other areas of tissue engineering, affects cell adhesion, activity, and expression of RPE cells. Though more exploration is needed, this begins to lay a foundation for optimizing scaffold rigidity to promote long-term success of RPE scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1260-1266, 2017.

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Experimental transplantation of human retinal pigment epithelial cells on collagen substrates

Cited by 3 publications

References 14 publications

Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model

Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model

Amniotic membrane as support for human retinal pigment epithelium (RPE) cell growth

The influence of substrate modulus on retinal pigment epithelial cells

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