The Application of Biomaterials to Tissue Engineering Neural Retina and Retinal Pigment Epithelium

Hunt, Nicola; Hallam, Dean; Chichagova, Valeria; Steel, David; Lako, Majlinda

doi:10.1002/adhm.201800226

Cited by 35 publications

(35 citation statements)

References 204 publications

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“…Glaucoma, which affects the inner retina, and diabetic retinopathy, which ultimately affects all retinal layers, are among other highly prevalent retinal diseases. Cell-based therapies in ophthalmology are based on the combined use of epithelial cells [such as retinal pigment epithelium (RPE) cells] and mesenchymal stem cells (MSCs) 13 . The RPE is believed to play a central role in retinal diseases associated with aging 14 .…”

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confidence: 99%

Cell spheroid fusion: beyond liquid drops model

Kosheleva

Efremov

Shavkuta

et al. 2020

Sci Rep

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Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates-spheroids-have become widely used model objects in the study of this phenomenon. existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. this discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation. Modern approaches to the rapidly evolving fields of regenerative medicine and tissue engineering are closely associated with the development and formation of tissue-engineered constructions, where cellular components play a crucial role 1-3. Monolayer cell culture is the most widely used approach to the growing and studying of cells in vitro. Nevertheless, 2D culture conditions cause cell flattening and remodeling of the cell's internal structure, which can eventually affect the gene expression 4. On the other hand, 3D cell culture better reflects the in vivo microenvironment both morphologically and physiologically. The extra dimension which 3D cell cultures have, compared to monolayers, helps to establish intercellular junctions, to reorganize the cytoskeleton, to polarize and to differentiate in conditions similar to native tissue conditions 5. Multicellular spheroids obtained under nonadhesive conditions represent one possible 3D cell culture system. There is a great deal of unexplored potential in spheroid-based research, as tissue engineering using spheroids is a relatively new field 6-8. Three-dimensional bioprinting of scaffold-based and scaffold-free tissue-engineered constructions is widely used for tissue substitution and modeling of organs-on-chips 9-12. Cell spheroids with prefabricated intercellular junctions and extracellular matrix provide a new promising type of bioinks suitable for processing by an

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confidence: 99%

Cell spheroid fusion: beyond liquid drops model

Kosheleva

Efremov

Shavkuta

et al. 2020

Sci Rep

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“…The complexity of progenitor cell movement presents distinct challenges to retinal regeneration because heterogeneous retinal clusters are comprised of cells of neuronal and glial lineages whose spatial organization, and their effects on RPC migration, remain incompletely understood [5,16]. While contemporary cell replacement strategies have utilized a growing number of transplantable biomaterials to aid viability of transplanted cells [17,18,19], inadequate and/or misdirected cell migration into damaged retina has been cited as a primary factor in the inability to achieve synaptic integration and restore vision [20,21,22,23]. Bio-engineering techniques and approaches with which to understand how the migratory responses of transplanted RPCs are mediated by their interactions with one another, soluble chemotactic stimuli, and extracellular substrate(s) will, thereby, greatly enrich retinal transplantation strategies.…”

Section: Introductionmentioning

confidence: 99%

Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System

Pena

Zhang

Majeska

et al. 2019

Cells

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Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insufficient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to our understanding of retinogenesis and the development of effective, cell-based approaches to retinal replacement. The current article describes a new bio-engineering approach to investigate the migratory responses of innate collections of RPCs upon extracellular substrates by combining microfluidics with the well-established invertebrate model of Drosophila melanogaster. Experiments utilized microfluidics to investigate how the composition, size, and adhesion of RPC clusters on defined extracellular substrates affected migration to exogenous chemotactic signaling. Results demonstrated that retinal cluster size and composition influenced RPC clustering upon extracellular substrates of concanavalin (Con-A), Laminin (LM), and poly-L-lysine (PLL), and that RPC cluster size greatly altered collective migratory responses to signaling from Fibroblast Growth Factor (FGF), a primary chemotactic agent in Drosophila. These results highlight the significance of examining collective cell-biomaterial interactions on bio-substrates of emerging biomaterials to aid directional migration of transplanted cells. Our approach further introduces the benefits of pairing genetically controlled models with experimentally controlled microenvironments to advance cell replacement therapies.

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“…In all of the photoreceptor replacement strategies presented in this review, the photoreceptor morphological and functional maturation is still unsatisfactory in the transplanted cells, despite the expression of mature photoreceptor markers. Engineering scaffolds to support the photoreceptor maturation and polarization, as largely developed for RPE cell replacement strategies (Ben M'Barek et al, 2017;da Cruz et al, 2018;Hunt et al, 2018;Kashani et al, 2018), have started being developed in attempt to overcome these problems ( Figure 5).…”

Section: Futures Directions and Conclusionmentioning

confidence: 99%

Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach

Gagliardi

M’Barek

Goureau

2019

Progress in Retinal and Eye Research

100

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The human retina fails to regenerate and cell-based therapies offer options for treatment of blinding retinal diseases, such as macular degeneration and retinitis pigmentosa (RP). The last decade has witnessed remarkable advances in generation of retinal cells and retinal tissue from human pluripotent stem cells (PSCs). The development of 3D culture systems allowing generation of human retinal organoids has substantially increased the access to human material for future clinical applications aiming at replacing the lost photoreceptors in retinal degenerative diseases. This review outlines the advances that have been made toward generation and characterization of transplantable photoreceptors from PSCs and summarizes the current status of PSC-based preclinical studies for photoreceptor replacement conducted in animal models. Considering the recent turning point in our understanding of donor photoreceptor integration, this review focuses on the most crucial obstacles that hinder the photoreceptor replacement, discusses the most promising strategies to overcome them in the future, and provides a perspective on the approaching advancement in the application of PSC technology for treatment of photoreceptor degenerative diseases.

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The Application of Biomaterials to Tissue Engineering Neural Retina and Retinal Pigment Epithelium

Cited by 35 publications

References 204 publications

Cell spheroid fusion: beyond liquid drops model

Cell spheroid fusion: beyond liquid drops model

Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System

Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach

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