Development of high-throughput lacrimal gland organoid platforms for drug discovery in dry eye disease

Rodboon, Teerapat; Yodmuang, Supansa; Chaisuparat, Risa; Ferreira, João N.

doi:10.1016/j.slasd.2021.11.002

Cited by 13 publications

(10 citation statements)

References 83 publications

(96 reference statements)

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“…Mice Ace2 and Tmprss2 are genetically distant from humans and thus display distinct SARS-CoV-2 binding affinity [ 14 , 15 ]; however, it could also undergo an altered regulation of expression [ 76 , 77 ]. Moreover, mice and human eyes also show different anatomical features [ 78 , 79 ], particularly evident in the Harderian glands, which are largely absent in the adult human [ 68 , 80 ]. These species-related particularities must, therefore, be considered when comparing and interpreting ocular symptoms between mice and humans following SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Brechbühl

Ferreira

Lópes

et al. 2023

Viruses

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The COVID-19 pandemic has engendered significant scientific efforts in the understanding of its infectious agent SARS-CoV-2 and of its associated symptoms. A peculiar characteristic of this virus lies in its ability to challenge our senses, as its infection can lead to anosmia and ageusia. While ocular symptoms, such as conjunctivitis, optic neuritis or dry eyes, are also reported after viral infection, they have lower frequencies and severities, and their functional development is still elusive. Here, using combined technical approaches based on histological and gene profiling methods, we characterized the expression of SARS-CoV-2 binding sites (Ace2/Tmprss2) in the mouse eye. We found that ACE2 was ectopically expressed in subtissular ocular regions, such as in the optic nerve and in the Harderian/intraorbital lacrimal glands. Moreover, we observed an important variation of Ace2/Tmprss2 expression that is not only dependent on the age and sex of the animal, but also highly heterogenous between individuals. Our results thus give new insight into the expression of SARS-CoV-2 binding sites in the mouse eye and propose an interpretation of the human ocular-associated symptoms linked to SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Brechbühl

Ferreira

Lópes

et al. 2023

Viruses

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“…PX‐478, a HIF‐1α inhibitor, was employed to treat human islet organoids with chronic high glucose exposure, enabling the glucose‐induced insulin secretion stimulation index increase, which was considered as a potential antidiabetic agent 224 . Moreover, the lacrimal gland organoids are reported as promising tools that allow high‐content drug screening 225,226 …”

Section: Biomedical Applications Of Organoidsmentioning

confidence: 99%

Organoids: The current status and biomedical applications

Yang

Kung

et al. 2023

MedComm

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Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large‐scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

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“…Previously, our research groups have successfully generated reproducible and functional epithelial LG-or SG-like organoids via M3DB platforms [24,32]. Herein, a protocol is proposed for creating preclinical disease models with aging multi-omic signatures for LG/SG organoids.…”

Section: Plos Onementioning

confidence: 99%

“…However, phenotypic and functional observations indicate that rodent models have many limitations since they poorly represent pathophysiological mechanisms occurring in human craniofacial glands [17,[19][20][21]. Previously, anatomical and histological similarities have been reported between porcine and human LG and SG [22][23][24]. Also, the human resemblance of vascular and immune systems (as well as pathogenesis processes) with their porcine counterparts is remarkable and make porcine models suitable towards future clinical studies targeting DED or DMS therapies [22,23,25,26].…”

Section: Introductionmentioning

confidence: 99%

“…Previously, our research group has established a successful strategy to assemble innervated functional epithelial SG organoids expressing acinar and ductal epithelial markers using a novel magnetic 3D bioassembly platforms with human and porcine primary cells [32,33]. One of these nano-based platforms is named magnetic 3D bioprinting (M3DB) and can also be applied in the biofabrication of consistent and scalable LG organoids with high cell viability [24]. One of our research groups have also generated aging models using etoposide treatment to induce chemical mutagenesis and cellular senescence [34].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Magnetic bioassembly platforms for establishing craniofacial exocrine gland organoids as aging in vitro models

et al. 2022

Self Cite

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A multitude of aging-related factors and systemic conditions can cause lacrimal gland (LG) or salivary gland (SG) hypofunction leading to degenerative dry eye disease (DED) or dry mouth syndrome, respectively. Currently, there are no effective regenerative therapies that can fully reverse such gland hypofunction due to the lack of reproducible in vitro aging models or organoids required to develop novel treatments for multi-omic profiling. Previously, our research group successful developed three-dimensional (3D) bioassembly nanotechnologies towards the generation of functional exocrine gland organoids via magnetic 3D bioprinting platforms (M3DB). To meet the needs of our aging Asian societies, a next step was taken to design consistent M3DB protocols to engineer LG and SG organoid models with aging molecular and pathological features. Herein, a feasible step-by-step protocol was provided for producing both LG and SG organoids using M3DB platforms. Such protocol provided reproducible outcomes with final organoid products resembling LG or SG native parenchymal epithelial tissues. Both acinar and ductal epithelial compartments were prominent (21 ± 4.32% versus 42 ± 6.72%, respectively), and could be clearly identified in these organoids. Meanwhile, these can be further developed into aging signature models by inducing cellular senescence via chemical mutagenesis. The generation of senescence-like organoids will be our ultimate milestone aiming towards high throughput applications for drug screening and discovery, and for gene therapy investigations to reverse aging.

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Development of high-throughput lacrimal gland organoid platforms for drug discovery in dry eye disease

Cited by 13 publications

References 83 publications

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Organoids: The current status and biomedical applications

Magnetic bioassembly platforms for establishing craniofacial exocrine gland organoids as aging in vitro models

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