Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films

Calejo, Maria Teresa; Saari, Jaakko; Vuorenpää, Hanna; Vuorimaa‐Laukkanen, Elina; Kallio, Pasi; Aalto‐Setälä, Katriina; Miettinen, Susanna; Skottman, Heli; Kellomäki, Minna; Juuti‐Uusitalo, Kati

doi:10.1016/j.actbio.2019.11.002

Cited by 20 publications

(16 citation statements)

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“…It remains unclear whether mutant TIMP3 may be less effective at inhibiting VEGF binding to VEGFR2, favouring angiogenesis; however, the available data in this area remain contradictory [26,47,48]. Differentiation of endothelial cells from SFD-hiPSCs, and their co-culture with SFD-hiPSC-RPE, could be used to generate a patient-specific in vitro three-dimensional model that mimics the RPEchoroidal interface, providing new insights into SFD pathobiology [49,50]. Furthermore, extrapolation of these findings to an hiPSC-RPE model of AMD, or with gene-corrected isogenic control lines, poses an interesting future research direction.…”

Section: Discussionmentioning

confidence: 99%

In vitro stem cell modelling demonstrates a proof‐of‐concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy

Hongisto

Dewing

Christensen

et al. 2020

The Journal of Pathology

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Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disease of the macula that leads to bilateral loss of central vision and is caused by mutations in the TIMP3 gene. However, the mechanisms by which TIMP3 mutations cause SFD are poorly understood. Here, we generated human induced pluripotent stem cell‐derived retinal pigmented epithelial (hiPSC‐RPE) cells from three SFD patients carrying TIMP3 p.(Ser204Cys) and three non‐affected controls to study disease‐related structural and functional differences in the RPE. SFD‐hiPSC‐RPE exhibited characteristic RPE structure and physiology but showed significantly reduced transepithelial electrical resistance associated with enriched expression of cytoskeletal remodelling proteins. SFD‐hiPSC‐RPE exhibited basolateral accumulation of TIMP3 monomers, despite no change in TIMP3 gene expression. TIMP3 dimers were observed in both SFD and control hiPSC‐RPE, suggesting that mutant TIMP3 dimerisation does not drive SFD pathology. Furthermore, mutant TIMP3 retained matrix metalloproteinase activity. Proteomic profiling showed increased expression of ECM proteins, endothelial cell interactions and angiogenesis‐related pathways in SFD‐hiPSC‐RPE. By contrast, there were no changes in VEGF secretion. However, SFD‐hiPSC‐RPE secreted higher levels of monocyte chemoattractant protein 1, PDGF and angiogenin. Our findings provide a proof‐of‐concept that SFD patient‐derived hiPSC‐RPE mimic mature RPE cells and support the hypothesis that excess accumulation of mutant TIMP3, rather than an absence or deficiency of functional TIMP3, drives ECM and angiogenesis‐related changes in SFD. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

In vitro stem cell modelling demonstrates a proof‐of‐concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy

Hongisto

Dewing

Christensen

et al. 2020

The Journal of Pathology

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“…As RPE and choroid endothelium are known to interact synergistically, [92][93][94]96,98 development of choroid-RPE cocultures is an attractive option both for in vitro modeling and for transplantation. 122 The ideal rationally designed Bruch's membrane would have a permeability sufficient to allow metabolite diffusion between cell layers while maintaining structural integrity to physically separate choroidal endothelium and RPE. 123 It would allow cell tethering to its surface while having a stiffness which could be physically tuned to the optimum for RPE on one side and choriocapillaris on the other.…”

Section: Biosynthetic Bruch's Membranementioning

confidence: 99%

“…126 Ex vivo Bruch's membrane from individuals with outer retinal disease may serve in coculture models of these diseases. 127 Other physical properties which have been investigated are porosity, wettability, and ion diffusion capacity in a variety of synthetic and natural explants (reviewed in detail here) 128 and using a variety of surface coating to facilitate cell adhesion 122,123,129,130 ; however, these studies have not investigated stiffness or tethering properties. Unsurprisingly, several polymers and several surface coatings containing ECM proteins such as collagens and laminins were found to be suitable for culture of hESC-derived RPE, although the identification of specific conditions which optimize RPE function have been equivocal.…”

Section: Biosynthetic Bruch's Membranementioning

confidence: 99%

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Ghareeb

Lako

Steel

2020

Stem Cells Translational Medicine

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Stem cell‐derived retinal organoids offer the opportunity to cure retinal degeneration of wide‐ranging etiology either through the study of in vitro models or the generation of tissue for transplantation. However, despite much work in animals and several human pilot studies, satisfactory therapies have not been developed. Two major challenges for retinal regenerative medicine are (a) physical cell‐cell interactions, which are critical to graft function, are not formed and (b) the host environment does not provide suitable queues for development. Several strategies offer to improve the delivery, integration, maturation, and functionality of cell transplantation. These include minimally invasive delivery, biocompatible material vehicles, retinal cell sheets, and optogenetics. Optimizing several variables in animal models is practically difficult, limited by anatomical and disease pathology which is often different to humans, and faces regulatory and ethical challenges. High‐throughput methods are needed to experimentally optimize these variables. Retinal organoids will be important to the success of these models. In their current state, they do not incorporate a representative retinal pigment epithelium (RPE)‐photoreceptor interface nor vascular elements, which influence the neural retina phenotype directly and are known to be dysfunctional in common retinal diseases such as age‐related macular degeneration. Advanced coculture techniques, which emulate the RPE‐photoreceptor and RPE‐Bruch's‐choriocapillaris interactions, can incorporate disease‐specific, human retinal organoids and overcome these drawbacks. Herein, we review retinal coculture models of the neural retina, RPE, and choriocapillaris. We delineate the scientific need for such systems in the study of retinal organogenesis, disease modeling, and the optimization of regenerative cell therapies for retinal degeneration.

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“…Functional groups selectively located in the pores of some complex membrane materials also benefited the preparation of selective cell adhesion surface. [ 139 ] Martinez‐Campos et al . [ 140 ] prepared two kinds of block polymers through ATRP, as shown in Figure 15.…”

Section: Application Of Bf Membranementioning

confidence: 99%

Ordered Honeycomb‐Pattern Membrane^†

Yuan

Dai

et al. 2020

Chin. J. Chem.

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Ordered porous membranes have wide and important application prospects in the fields of filtration, separation, catalysis, biomedicine, etc., and have attracted growing interest in the field of material science. Among diverse membrane preparation approaches, breath pattern method has been widely concerned due to its simplicity in the preparation, ease in tuning the structure/property and functionality of formed membranes, and broad utility for various polymers. With the development of material design, the application spectrum of breath figure membrane has been greatly expanded. However, since the pore morphology of porous membrane is influenced by many factors, the controlling mechanism of normalization has not been clear yet. In this paper, the research progress of film-forming materials in recent years is reviewed, and the correlation between pore formation and pore morphology is discussed in details. This information will provide a systematic and in-depth perspective for research in this filed and an important guideline for the preparation of the ordered porous films with divergent applications. Hua Yuan (left) is an associate professor in College of Materials Science and Engineering, Qingdao University, China. She received her doctorate from Shandong University in China in 2013. She is mainly engaged in the research of carbon fiber, composites and microfiltration membrane. Guangzhen Li (middle) is a graduate student in the College of Materials Science and Engineering, Qingdao University, China. He graduated with a bachelor's degree in engineering from Qingdao University in 2019. His current research focuses on the structural design and functionalization of membrane materials. Enhao Dai (right) is a graduate student of the College of Materials Science and Engineering of Qingdao University. He received a bachelor's degree in engineering from Yantai University in 2018. Currently, he mainly studies carbon fiber modification.

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Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films

Cited by 20 publications

References 73 publications

In vitro stem cell modelling demonstrates a proof‐of‐concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy

In vitro stem cell modelling demonstrates a proof‐of‐concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Ordered Honeycomb‐Pattern Membrane^†

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Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films

Cited by 20 publications

References 73 publications

In vitro stem cell modelling demonstrates a proof‐of‐concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy

In vitro stem cell modelling demonstrates a proof‐of‐concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Ordered Honeycomb‐Pattern Membrane†

Contact Info

Product

Resources

About

Ordered Honeycomb‐Pattern Membrane^†