SARS-CoV-2 induces barrier damage and inflammatory responses in the human iPSC-derived intestinal epithelium

Yamada, Shigeru; Noda, Takamasa; Okabe, Kaori; Yanagida, Shota; Nishida, Motohiro; Kanda, Yasunari

doi:10.1016/j.jphs.2022.04.010

Cited by 19 publications

(23 citation statements)

References 47 publications

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“…8) Caco-2 cells were obtained from the American Type Culture Collection (Manassas, VA, U.S.A.) and were cultured as previously described. 2,3) Intestinal organoids were differentiated from human iPSCs according to our previous protocol 2,3) (Fig. 1B).…”

Section: Methodsmentioning

confidence: 99%

“…In this regard, we have previously reported that human induced pluripotent stem cell (iPSC)-derived intestinal organoids can provide a useful tool for investigating the physiological function of the intestinal epithelium. 2,3) Vitamin D 3 (VD 3 ) is an essential nutrient that can be metabolized or absorbed from the diet, and it is well established that 1α,25-dihydroxyvitamin D 3 , a metabolically activated form of vitamin D 3 , has effects on a range of different biological processes via the vitamin D receptor (VDR), a member of the nuclear hormone receptor superfamily of ligand-inducible transcription factors. 4) To date, a number of VDR ligands that can activate this receptor have been developed, examples of which include VD 3 derivatives that have been reported to have effects on inflammatory responses and the regulation of cholesterol synthesis in intestinal epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Lithocholic Acid Derivative Upregulates Detoxification-Related Genes in Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids

Yamada

Masuno

Kagechika

et al. 2022

Biological & Pharmaceutical Bulletin

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Vitamin D is a fat-soluble micronutrient that plays essential roles in a range of biological processes, including cell proliferation, inflammation, and metabolism. In this study, we investigated the effects of a novel synthetic lithocholic acid derivative with vitamin D activity (Dcha-20) on pharmacokinetic gene expression in human induced pluripotent stem cell-derived intestinal organoids. Compared with vitamin D 3 treatment, Dcha-20 was found to upregulate the expression and enzyme activity of the drug-metabolizing enzyme CYP3A4, an indicator of intestinal functional maturation. In addition, Dcha-20 specifically increased expression levels of the xenobiotic detoxification enzyme UGT1A and excretion transporter MRP2. These results suggest that Dcha-20 promotes activity of the intrinsic defense system of the intestinal epithelium.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Lithocholic Acid Derivative Upregulates Detoxification-Related Genes in Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids

Yamada

Masuno

Kagechika

et al. 2022

Biological & Pharmaceutical Bulletin

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“…In particular, the IL-6 and TNF genes and C-X-C motif chemokine ligand 10 (CXCL10), a chemoattractant for NK cells and T cells and a monocyte inducer, were significantly upregulated ( 60 ). Gene set enrichment analysis in pluripotent stem cells derived from small intestinal epithelial cells or intestinal organoids from SARS-CoV-2 infection models also revealed increased expression of IL-1β, IL-6, CXCL10, C-C motif chemokine ligand 5 (CCL5, chemoattractant for monocytes), and significant upregulation of IL-6 and the nuclear factor-κB (NF-κB) pathway ( 61 , 62 ). Quantification of cytokines in the stool of patients hospitalized for COVID-19 revealed higher IL-8, IL-18, and lower IL-10 levels ( 63 , 64 ).…”

Section: Sars-cov-2-mediated Changes In the Intestinal Immunological ...mentioning

confidence: 99%

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential

et al. 2023

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Although coronavirus disease 2019 (COVID-19) is primarily associated with mild respiratory symptoms, a subset of patients may develop more complicated disease with systemic complications and multiple organ injury. The gastrointestinal tract may be directly infected by SARS-CoV-2 or secondarily affected by viremia and the release of inflammatory mediators that cause viral entry from the respiratory epithelium. Impaired intestinal barrier function in SARS-CoV-2 infection is a key factor leading to excessive microbial and endotoxin translocation, which triggers a strong systemic immune response and leads to the development of viral sepsis syndrome with severe sequelae. Multiple components of the gut immune system are affected, resulting in a diminished or dysfunctional gut immunological barrier. Antiviral peptides, inflammatory mediators, immune cell chemotaxis, and secretory immunoglobulins are important parameters that are negatively affected in SARS-CoV-2 infection. Mucosal CD4+ and CD8+ T cells, Th17 cells, neutrophils, dendritic cells, and macrophages are activated, and the number of regulatory T cells decreases, promoting an overactivated immune response with increased expression of type I and III interferons and other proinflammatory cytokines. The changes in the immunologic barrier could be promoted in part by a dysbiotic gut microbiota, through commensal-derived signals and metabolites. On the other hand, the proinflammatory intestinal environment could further compromise the integrity of the intestinal epithelium by promoting enterocyte apoptosis and disruption of tight junctions. This review summarizes the changes in the gut immunological barrier during SARS-CoV-2 infection and their prognostic potential.

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“…COVID-19 causes gastrointestinal symptoms such as diarrhea, nausea, and vomiting, as well as respiratory failure. In this study, human-induced pluripotent stem cell (iPSC)-derived small intestinal epithelial cells (iPSC-SIEC) could be employed as a SARS-CoV-2 infection model ( Yamada et al, 2022 ). SARS-CoV-2 infection was found in absorptive and Paneth cells from iPSC-SIECs.…”

Section: Therapeutic Approaches Using Mscs and Ipscs In Covid-19mentioning

confidence: 99%

“…The disruption of the mucosal barrier and inflammatory reactions after SARS-CoV-2 infection could have caused these gut injuries. Remdesivir suppresses the cytokine storm in patients with COVID-19, implying that remdesivir reduces patients’ gastrointestinal problems ( Yamada et al, 2022 ).…”

Section: Therapeutic Approaches Using Mscs and Ipscs In Covid-19mentioning

confidence: 99%

MSCs vs. iPSCs: Potential in therapeutic applications

Thanaskody¹,

Jusop²,

Tye³

et al. 2022

Front. Cell Dev. Biol.

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Over the past 2 decades, mesenchymal stem cells (MSCs) have attracted a lot of interest as a unique therapeutic approach for a variety of diseases. MSCs are capable of self-renewal and multilineage differentiation capacity, immunomodulatory, and anti-inflammatory properties allowing it to play a role in regenerative medicine. Furthermore, MSCs are low in tumorigenicity and immune privileged, which permits the use of allogeneic MSCs for therapies that eliminate the need to collect MSCs directly from patients. Induced pluripotent stem cells (iPSCs) can be generated from adult cells through gene reprogramming with ectopic expression of specific pluripotency factors. Advancement in iPS technology avoids the destruction of embryos to make pluripotent cells, making it free of ethical concerns. iPSCs can self-renew and develop into a plethora of specialized cells making it a useful resource for regenerative medicine as they may be created from any human source. MSCs have also been used to treat individuals infected with the SARS-CoV-2 virus. MSCs have undergone more clinical trials than iPSCs due to high tumorigenicity, which can trigger oncogenic transformation. In this review, we discussed the overview of mesenchymal stem cells and induced pluripotent stem cells. We briefly present therapeutic approaches and COVID-19-related diseases using MSCs and iPSCs.

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SARS-CoV-2 induces barrier damage and inflammatory responses in the human iPSC-derived intestinal epithelium

Cited by 19 publications

References 47 publications

A Novel Lithocholic Acid Derivative Upregulates Detoxification-Related Genes in Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids

A Novel Lithocholic Acid Derivative Upregulates Detoxification-Related Genes in Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential

MSCs vs. iPSCs: Potential in therapeutic applications

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