An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation

Luo, Ziming; Zhong, Xiufeng; Li, Kaijing; Xie, Bing; Liu, Yuchun; Ye, Meifang; Li, Kang; Xu, Chaochao; Ge, Junbo

doi:10.1002/stem.2890

Cited by 34 publications

(36 citation statements)

References 43 publications

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“…The organoid features displayed by F49B7 suggest that screening of iPSC lines is an effective way to generate organoids with specific organ features. In addition, iPSC lines can be guided to differentiate to retinal organoids by adding growth factors (Capowski et al, 2019;Luo et al, 2018;Nakano et al, 2012). Organoids obtained with reference lines such as F49B7 will allow the study of human retina development and the effect of physical or chemical risk factors on specific cell types.…”

Section: Multilayered Retinal Organoidsmentioning

confidence: 99%

Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map

Cowan

Renner

Gennaro

et al. 2019

Preprint

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How closely human organoids recapitulate cell-type diversity and cell-type maturation of their target organs is not well understood. We developed human retinal organoids with multiple nuclear and synaptic layers. We sequenced the RNA of 158,844 single cells from these organoids at six developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable 'developed' state at a rate similar to human retina development in vivo and the transcriptomes of organoid cell types converged towards the transcriptomes of adult peripheral retinal cell types. The expression of disease-associated genes was significantly cell-type specific in adult retina and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in adult human retinas.

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Section: Multilayered Retinal Organoidsmentioning

confidence: 99%

Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map

Cowan

Renner

Gennaro

et al. 2019

Preprint

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“…The hiPS cells were passaged every 5-6 days by enzymatic digestion with 1 mM EDTA at 80% confluence. The hiPSCs were differentiated to retinal tissue based on previously established protocol with minor modifications [37,38]. Briefly, hiPSC were dissociated into small colonies and cultured in mTeSR1 medium (STEMCELL Technologies, Vancouver, Canada) supplemented with 10 μM Blebbistatin (Sigma, USA).…”

Section: Differentiation Of Human Ips Cells Into 3-d Retinal Cupsmentioning

confidence: 99%

BAM15 attenuates transportation-induced apoptosis in iPS-differentiated retinal tissue

Tang

Luo

et al. 2019

Stem Cell Res Ther

Self Cite

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Background: BAM15 is a novel mitochondrial protonophore uncoupler capable of protecting mammals from acute renal ischemic-reperfusion injury and cold-induced microtubule damage. The purpose of our study was to investigate the effect of BAM15 on apoptosis during 5-day transportation of human-induced pluripotent stem (hiPS)-differentiated retinal tissue. Methods: Retinal tissues of 30 days and 60 days were transported with or without BAM15 for 5 days in the laboratory or by real express. Immunofluorescence staining of apoptosis marker cleaved caspase3, proliferation marker Ki67, and neural axon marker NEFL was performed. And expression of apoptotic-related factors p53, NFkappaB, and TNF-a was detected by real-time PCR. Also, location of ganglion cells, photoreceptor cells, amacrine cells, and precursors of neuronal cell types in retinal tissue was stained by immunofluorescence after transportation. Furthermore, cell viability was assessed by CCK8 assay.Results: Results showed transportation remarkably intensified expression of apoptotic factor cleaved caspase3, p53, NFkappaB, and TNF-a, which could be reduced by supplement of BAM15. In addition, neurons were severely injured after transportation, with axons manifesting disrupted and tortuous by staining NEFL. And the addition of BAM15 in transportation was able to protect neuronal structure and increase cell viability without affecting subtypes cells location of retinal tissue. Conclusions: BAM15 might be used as a protective reagent on apoptosis during transporting retinal tissues, holding great potential in research and clinical applications.

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“…42 In addition, adding Wnt signaling antagonist Dickkopf-related protein 1 (DKK-1) could induce the formation of 3D optic vesicles from human-induced pluripotent stem cells that were normally not able to selforganize and differentiate toward retinal tissue. 43 Finally, to enhance connectivity of different neural parts, for example, the neuroepithelium-derived Purkinje cells, interneurons, granule cells, and cerebellar nuclei neurons from the rhombic lip, fibroblast growth factor 19 (FGF19), and stromal cell-derived factor 1 (SDF1) were supplemented. This led to the generation of the continuous connected cerebellar plate from human ESC-derived cerebellar progenitors, creating an early human cerebellum resembling the first trimester.…”

Section: Boosting Cells' Intrinsic Capacity To Self-organize: Small Mmentioning

confidence: 99%

Building Complex Life Through Self-Organization

Sthijns¹,

LaPointe²,

Blitterswijk³

2019

Tissue Engineering Part A

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Cells are inherently conferred with the ability to self-organize into the tissues and organs comprising the human body. Self-organization can be recapitulated in vitro and recent advances in the organoid field are just one example of how we can generate small functioning elements of organs. Tissue engineers can benefit from the power of self-organization and should consider how they can harness and enhance the process with their constructs. For example, aggregates of stem cells and tissue-specific cells benefit from the input of carefully selected biomolecules to guide their differentiation toward a mature phenotype. This can be further enhanced by the use of technologies to provide a physiological microenvironment for self-organization, enhance the size of the constructs, and enable the long-term culture of self-organized structures. Of importance, conducting selforganization should be limited to fine-tuning and should avoid over-engineering that could counteract the power of inherent cellular self-organization.Self-organization is a powerful innate feature of cells that can be fine-tuned but not over-engineered to create new tissues and organs.

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An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation

Cited by 34 publications

References 43 publications

Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map

Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map

BAM15 attenuates transportation-induced apoptosis in iPS-differentiated retinal tissue

Building Complex Life Through Self-Organization

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