scholarly journals Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids

2021 ◽  
Vol 22 (3) ◽  
pp. 1320
Author(s):  
Henkie Isahwan Ahmad Mulyadi Lai ◽  
Shih-Jie Chou ◽  
Yueh Chien ◽  
Ping-Hsing Tsai ◽  
Chian-Shiu Chien ◽  
...  
Keyword(s):  
Stem Cell ◽  
Angiotensin Converting Enzyme ◽  
Pluripotent Stem Cell ◽  
Expression System ◽  
Induced Pluripotent Stem Cell ◽  
Target Tissue ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Monolayer Cultures ◽  
Induced Pluripotent

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

scholarly journals SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes

2020 ◽  
Vol 116 (14) ◽  
pp. 2207-2215 ◽  
Author(s):  
Denisa Bojkova ◽  
Julian U G Wagner ◽  
Mariana Shumliakivska ◽  
Galip S Aslan ◽  
Umber Saleem ◽  
...  
Keyword(s):  
Stem Cell ◽  
Angiotensin Converting Enzyme ◽  
Pluripotent Stem Cell ◽  
Cardiac Injury ◽  
Induced Pluripotent Stem Cell ◽  
Viral Rna ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Induced Pluripotent

Abstract Aims Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection. Methods and results Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir. Conclusion This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.

scholarly journals An induced pluripotent stem cell-mediated and integration-free factor VIII expression system

2013 ◽  
Vol 431 (2) ◽  
pp. 336-341 ◽  
Author(s):  
Yuwna Yakura ◽  
Chie Ishihara ◽  
Hajime Kurosaki ◽  
Yasuhiro Kazuki ◽  
Norio Komatsu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Factor Viii ◽  
Pluripotent Stem Cell ◽  
Expression System ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

Use of 3D culture systems to generate human induced pluripotent stem cell-derived [beta]-cells in vitro

2018 ◽  
Author(s):  
Fantuzzi Federica ◽  
Toivonen Sanna ◽  
Schiavo Andrea Alex ◽  
Pachera Nathalie ◽  
Rajaei Bahareh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Beta Cells ◽  
Pluripotent Stem Cell ◽  
3D Culture ◽  
Induced Pluripotent Stem Cell ◽  
Culture Systems ◽  
Induced Pluripotent
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