Generation of hESC-derived retinal pigment epithelium on biopolymer coated polyimide membranes

Subrizi, Astrid; Hiidenmaa, Hanna; Ilmarinen, Tanja; Nymark, Soile; Dubruel, Peter; Uusitalo, Hannu; Yliperttula, Marjo; Urtti, Arto; Skottman, Heli

doi:10.1016/j.biomaterials.2012.07.033

Cited by 67 publications

(57 citation statements)

References 35 publications

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“…23,33,36,37 Thus, one of the important tasks of transplanted hESC-RPE is to produce sufficient ECM to restore the functions of the damaged BM if no BM mimicking nonbiodegradable biomaterial is used with cells. 16,17 Previously, it has been shown that ECM affects the early stage differentiation of hPSCs into neural progenitors and neurons, 38 retinal progenitor cells, 39,40 and RPE cells. 41 In addition, different ECM proteins have been used in differentiation of hESC-RPE.…”

Section: Introductionmentioning

confidence: 99%

“…41 In addition, different ECM proteins have been used in differentiation of hESC-RPE. 42 Most of the current hPSC-RPE differentiation protocols utilize either xeno-derived substrates, such as MatrigelÔ, 43,44 gelatin, 4,12 and humanderived ECM proteins, 10,16 as attachment and culture matrices. 42 However, little is known about the effects of the ECM proteins on maturation of hESC-RPE epithelium, its barrier properties, and fine structure.…”

Section: Introductionmentioning

confidence: 99%

“…Grafting of intact and polarized RPE cell sheets, instead of cell injections, is considered as a more promising transplantation strategy. [14][15][16][17] Extracellular matrix (ECM) is a dynamic and complex environment that interacts with cells through cell surface receptors such as integrins. 18,19 Apart from the mechanical support and its role in cell adhesion, ECM binds soluble factors and regulates their distribution and presentation to cells.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Sorkio

Hongisto

Kaarniranta

et al. 2014

Tissue Engineering Part A

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Extracellular matrix (ECM) interactions play a vital role in cell morphology, migration, proliferation, and differentiation of cells. We investigated the role of ECM proteins on the structure and function of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells during their differentiation and maturation from hESCs into RPE cells in adherent differentiation cultures on several human ECM proteins found in native human Bruch's membrane, namely, collagen I, collagen IV, laminin, fibronectin, and vitronectin, as well as on commercial substrates of xeno-free CELLstartÔ and MatrigelÔ. Cell pigmentation, expression of RPE-specific proteins, fine structure, as well as the production of basal lamina by hESC-RPE on different protein coatings were evaluated after 140 days of differentiation. The integrity of hESC-RPE epithelium and barrier properties on different coatings were investigated by measuring transepithelial resistance. All coatings supported the differentiation of hESC-RPE cells as demonstrated by early onset of cell pigmentation and further maturation to RPE monolayers after enrichment. Mature RPE phenotype was verified by RPE-specific gene and protein expression, correct epithelial polarization, and phagocytic activity. Significant differences were found in the degree of RPE cell pigmentation and tightness of epithelial barrier between different coatings. Further, the thickness of self-assembled basal lamina and secretion of the key ECM proteins found in the basement membrane of the native RPE varied between hESC-RPE cultured on compared protein coatings. In conclusion, this study shows that the cell culture substrate has a major effect on the structure and basal lamina production during the differentiation and maturation of hESC-RPE potentially influencing the success of cell integrations and survival after cell transplantation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Sorkio

Hongisto

Kaarniranta

et al. 2014

Tissue Engineering Part A

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“…Specifically, the photoreceptors constantly undergo a renewal process where the tips of the photoreceptors containing a number of radical species, photo-damaged proteins and lipids are eliminated by the clearing action of RPE [10,57]. In this context, the assessment of the phagocytic capacity of RPE towards POS can be a valuable tool to evaluate the functionality of RPE cells cultured in vitro [8,14,[58][59][60]. In spite of clear morphological differences between epithelia on LS-and dip-coated scaffolds, dip-coated membranes showing more fusiform RPE cells typically associated with less mature phenotype [61], cells with phagocytic activity could be detected on all materials, regardless of the coating type.…”

Section: Discussionmentioning

confidence: 99%

Langmuir-Schaefer film deposition onto honeycomb porous films for retinal tissue engineering

et al. 2017

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Age-related macular degeneration (AMD) is the leading cause of vision loss in senior citizens in the developed world. The disease is characterised by the degeneration of a specific cell layer at the back of the eye -the retinal pigment epithelium (RPE), which is essential in retinal function. The most promising therapeutic option to restore the lost vision is considered to be RPE cell transplantation. This work focuses on the development of biodegradable biomaterials with similar properties to the native Bruch's membrane as carriers for RPE cells. In particular, the breath figure (BF) method was used to create semi-permeable microporous films, which were thereafter used as the substrate for the consecutive Langmuir-Schaefer (LS) deposition of highly organised layers of collagen type I and collagen type IV. The newly developed biomaterials were further characterised in terms of surface porosity, roughness, hydrophilicity, collagen distribution, diffusion properties and hydrolytic stability.Human embryonic stem cell-derived RPE cells (hESC-RPE) cultured on the biomaterials showed good adhesion, spreading and morphology, as well as the expression of specific protein markers. Cell function was additionally confirmed by the assessment of the phagocytic capacity of hESC-RPE.Throughout the study, microporous films consistently showed better results as cell culture materials for 2 hESC-RPE than dip-coated controls. This work demonstrates the potential of the BF-LS combined technologies to create biomimetic prosthetic Bruch's membranes for hESC-RPE transplantation.

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“…Natural membranes including biologically-derived basal lamina, amniotic membrane, Descemet's membrane and lens capsule have been used as substrates for RPE cells. 121,172 Additionally, artificial Bruch's membrane substrates including parylene films, 173,174 plasma polymers, 175 polyamide nanofibres, 176 polyester membranes, 177 polyimide, 178 and modified polytetrafluoroethylene 175 have been proposed. 179 However, the use of some types of artificial membranes carries the risk of biological contamination and disease transmission.…”

Section: Enhancing the Adhesion And Survival Of Transplanted Rpe Cellsmentioning

confidence: 99%

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

Heller

Martin

2014

Trans. Vis. Sci. Tech.

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Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cellderived RPE cells. However, the therapeutic success of transplantation of stem cellderived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.

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Generation of hESC-derived retinal pigment epithelium on biopolymer coated polyimide membranes

Cited by 67 publications

References 35 publications

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Langmuir-Schaefer film deposition onto honeycomb porous films for retinal tissue engineering

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

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