Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure

Ueno, Masaki; Toda, Munetoyo; Numa, Kohsaku; Tanaka, Hiroshi; Imai, Kojiro; Bush, John; Teramukai, Satoshi; Okumura, Naoki; Koizumi, Noriko; Yamamoto, Akihisa; Tanaka, Motomu; Sotozono, Chie; Hamuro, Junji; Kinoshita, Shigeru

doi:10.1016/j.ajo.2021.11.012

Cited by 25 publications

(19 citation statements)

References 33 publications

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“…2 We recently found that J o u r n a l P r e -p r o o f 20 functional phenotypes directly link to trans-endothelial fluid movement in mature CD44 -/dull hCEC SPs, 1,35,37 expressing AQP1, SLC4A11, and ZO-1. 38,39 Increases in cellular miR-184 and -24-3p in hCEC were inversely proportional to the decrease of CD44 expression (Fig. 3).…”

Section: Discussionmentioning

confidence: 84%

Cellular Interplay Through Extracellular Vesicle miR-184 Alleviates Corneal Endothelium Degeneration

Yamashita¹,

Asada²,

Ueno³

et al. 2022

Ophthalmology Science

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Section: Discussionmentioning

confidence: 84%

Cellular Interplay Through Extracellular Vesicle miR-184 Alleviates Corneal Endothelium Degeneration

Yamashita¹,

Asada²,

Ueno³

et al. 2022

Ophthalmology Science

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“…2 B); that is, the cHCECs are divided into subpopulations in which CD44 −/dull mature differentiated cells without cell-state transition (CST) are selectively applicable for cell-based therapy. 25 , 26 , 40 Flow cytometry analysis revealed that the majority of cHCECs showed CD166 + /CD24 − /CD26 − /CD44 −/dull /CD105 −/dull characteristics that mimic the cell surface markers of in vivo healthy-tissue HCECs ( Fig. 2 C).…”

Section: Resultsmentioning

confidence: 93%

Comprehensive Analysis Identified the Circadian Clock and Global Circadian Gene Expression in Human Corneal Endothelial Cells

Nakai

Tsuchiya

Koike

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate circadian clock oscillation and circadian global gene expression in cultured human corneal endothelial cells (cHCECs) to elucidate and assess the potential function of circadian regulation in HCECs. Methods In this study, we introduced a circadian bioluminescence reporter, Bmal1:luciferase ( Bmal1:luc ), into cHCECs and subsequently monitored real-time bioluminescence rhythms. RNA-sequencing data analysis was then performed using sequential time-course samples of the cHCECs to obtain a comprehensive understanding of the circadian gene expression rhythms. The potential relevance of rhythmically expressed genes was then assessed by systematic approaches using functional clustering and individual gene annotations. Results Bmal1:luc bioluminescence exhibited clear circadian oscillation in the cHCECs. The core clock genes and clock-related genes showed high-amplitude robust circadian messenger RNA (mRNA) expression rhythms in cHCECs after treatment with dexamethasone, and 329 genes that exhibited circadian mRNA expression rhythms were identified (i.e., genes involved in various physiological processes including glycolysis, mitochondrial function, antioxidative systems, hypoxic responses, apoptosis, and extracellular matrix regulation, which represent the physiological functions of HCECs). Conclusions Our findings revealed that cHCECs have a robust and functional circadian clock, and our discovery that a large number of genes exhibit circadian mRNA expression rhythms in cHCECs suggests a potential contribution of circadian regulation to fine-tune HCEC functions for daily changes in the environment.

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“…A recent landmark study conducted by our group has demonstrated that the intracameral injection of cHCECs can reverse corneal edema with stable clinical outcomes in patients with bullous keratopathy and Fuchs’ endothelial corneal dystrophy (FECD). 8 , 9 , 13 We have successfully distinguished between cHCEC SPs with high clinical efficacy (the SPs are described as effector cells) and those with low efficacy. The former elicited cellular phenotypes almost the same as those of fresh tissue HCEs, whereas the latter elicited a clear distinction from them.…”

Section: Discussionmentioning

confidence: 99%

“… 12 We have successfully identified cHCEC SPs with high clinical efficacy (occasionally described as effector cells) versus those with low clinical efficacy. 9 , 13 We have also specified the effector cell cHCEC SPs with CD133, CD105, CD90, CD44, CD26, CD24, and human leucocyte antigen (HLA)-DR as negative and CD166, HLA-ABC, and programmed cell death ligand 1 (PD-L1) as positive, as well as the manufacturing approach thereof. 12 , 14 , 15 …”

mentioning

confidence: 99%

Repressed miR-34a Expression Dictates the Cell Fate to Corneal Endothelium Failure

Hamuro

Asada

Ueno

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure

Cited by 25 publications

References 33 publications

Cellular Interplay Through Extracellular Vesicle miR-184 Alleviates Corneal Endothelium Degeneration

Cellular Interplay Through Extracellular Vesicle miR-184 Alleviates Corneal Endothelium Degeneration

Comprehensive Analysis Identified the Circadian Clock and Global Circadian Gene Expression in Human Corneal Endothelial Cells

Repressed miR-34a Expression Dictates the Cell Fate to Corneal Endothelium Failure

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