Cell-laden and orthogonal-multilayer tissue-engineered corneal stroma induced by a mechanical collagen microenvironment and transplantation in a rabbit model

Cui, Zekai; Zeng, Qiaolang; Liu, Shiwei; Zhang, Yanan; Zhu, Deliang; Guo, Yanjie; Xie, Mengyuan; Mathew, Sanjana; Cai, Dongqing; Zhang, Jun; Chen, Jiansu

doi:10.1016/j.actbio.2018.06.005

Cited by 33 publications

(18 citation statements)

References 60 publications

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“…The RNA-seq analysis was performed as previously described (Cui et al, 2018). Briefly, total RNA of organoids in RPiPSCs and NiPSCs was extracted.…”

Section: Methodsmentioning

confidence: 99%

Modeling Retinitis Pigmentosa: Retinal Organoids Generated From the iPSCs of a Patient With the USH2A Mutation Show Early Developmental Abnormalities

Guo

Wang

et al. 2019

Front. Cell. Neurosci.

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Retinitis pigmentosa (RP) represents a group of inherited retinopathies with early-onset nyctalopia followed by progressive photoreceptor degeneration causing irreversible vision loss. Mutations in USH2A are the most common cause of non-syndromic RP. Here, we reprogrammed induced pluripotent stem cells (iPSCs) from a RP patient with a mutation in USH2A (c.8559-2A > G/c.9127_9129delTCC). Then, multilayer retinal organoids including neural retina (NR) and retinal pigment epithelium (RPE) were generated by three-step “induction-reversal culture.” The early retinal organoids derived from the RP patient with the USH2A mutation exhibited significant defects in terms of morphology, immunofluorescence staining and transcriptional profiling. To the best of our knowledge, the pathogenic mutation (c.9127_9129delTCC) in USH2A has not been reported previously among RP patients. Notably, the expression of laminin in the USH2A mutation organoids was significantly lower than in the iPSCs derived from healthy, age- and sex-matched controls during the retinal organogenesis. We also observed that abnormal retinal neuroepithelium differentiation and polarization caused defective retinal progenitor cell development and retinal layer formation, disordered organization of NRs in the presence of the USH2A mutation. Furthermore, the USH2A mutation bearing RPE cells presented abnormal morphology, lacking pigmented foci and showing an apoptotic trend and reduced expression of specific makers, such as MITF, PEDF , and RPE65. In addition, the USH2A mutation organoids had lower expression of cilium-associated (especially CFAP43 , PIFO ) and dopaminergic synapse-related genes (including DLGAP1 , GRIK1 , SLC17A7 , and SLC17A8 ), while there was higher expression of neuron apoptotic process-related genes (especially HIF1A , ADARB1 , and CASP3 ). This study may provide essential assistance in the molecular diagnosis and screening of RP. This work recapitulates the pathogenesis of USH2A using patient-specific organoids and demonstrated that alterations in USH2A function due to mutations may lead to cellular and molecular abnormalities.

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“…The RNA-seq analysis was performed as previously described (Cui et al, 2018). Briefly, total RNA of organoids in RPiPSCs and NiPSCs was extracted.…”

Section: Methodsmentioning

confidence: 99%

Modeling Retinitis Pigmentosa: Retinal Organoids Generated From the iPSCs of a Patient With the USH2A Mutation Show Early Developmental Abnormalities

Guo

Wang

et al. 2019

Front. Cell. Neurosci.

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“…Although stromal cells (keratocytes) are dendritic shaped in the native cornea, they shift into spindle-shaped fibroblasts or polygonal corneal myofibroblast in serum. Despite this fact, it is observed that they shift to keratocyte cells in collagen after a week of culture with serum [214]. Cultured keratocyte cells on groove-patterned silk film also elongated towards the grooves and resulted in orderly aligned cells in comparison with cells cultured on unpatterned films.…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

Bioengineering Approaches for Corneal Regenerative Medicine

Mahdavi

Abdekhodaie

Mashayekhan

et al. 2020

Tissue Eng Regen Med

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BACKGROUND: Since the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments. METHODS: In this review, we first discussed the anatomy of the cornea and the required properties for reconstructing layers of the cornea. Regenerative approaches are divided into two main categories; using direct cell/growth factor delivery or using scaffold-based cell delivery. It is expected delivered cells migrate and integrate into the host tissue and restore its structure and function to restore vision. Growth factor delivery also has shown promising results for corneal surface regeneration. Scaffold-based approaches are categorized based on the type of scaffold, since it has a significant impact on the efficiency of regeneration, into the hydrogel and non-hydrogel based scaffolds. Various types of cells, biomaterials, and techniques are well covered. RESULTS: The most important characteristics to be considered for biomaterials in corneal regeneration are suitable mechanical properties, biocompatibility, biodegradability, and transparency. Moreover, a curved shape structure and spatial arrangement of the fibrils have been shown to mimic the corneal extracellular matrix for cells and enhance cell differentiation. CONCLUSION: Tissue engineering and regenerative medicine approaches showed to have promising outcomes for corneal regeneration. However, besides proper mechanical and optical properties, other factors such as appropriate sterilization method, storage, shelf life and etc. should be taken into account in order to develop an engineered cornea for clinical trials.

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“…High mechanical strength is essential for the survival of DPS grafts, as they need to withstand the tears caused by stitches tear during the surgery, as well as the membrane stresses caused by intraocular pressure and external forces. 43,44 In vitro, cell phenotypes and behaviors are greatly affected by the molecules released by ECM scaffolds. 45 The scleral ECM protein composition and the growth factor composition in the DPS may contribute to this effect.…”

Section: F I G U R Ementioning

confidence: 99%

Scleral defect repair using decellularized porcine sclera in a rabbit model

Wang

Zhao

et al. 2020

Xenotransplantation

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The sclera is the outermost layer of the ocular wall, and its main role is to protect the eyeball. 1,2 Its surface is covered by conjunctiva and fascia and does not have direct contact with the outside world. In addition, the sclera is mainly composed of dense interwoven collagen fibers and elastic fibers, with few cellular components and blood vessels. 3,4 These histological features indicate that when scleral

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Cell-laden and orthogonal-multilayer tissue-engineered corneal stroma induced by a mechanical collagen microenvironment and transplantation in a rabbit model

Cited by 33 publications

References 60 publications

Modeling Retinitis Pigmentosa: Retinal Organoids Generated From the iPSCs of a Patient With the USH2A Mutation Show Early Developmental Abnormalities

Modeling Retinitis Pigmentosa: Retinal Organoids Generated From the iPSCs of a Patient With the USH2A Mutation Show Early Developmental Abnormalities

Bioengineering Approaches for Corneal Regenerative Medicine

Scleral defect repair using decellularized porcine sclera in a rabbit model

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