Article ; Online: Long Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury.
2020 Volume 35, Issue 3, Page(s) 311–320
Abstract: ... a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and ... In this study, we successfully established long term cultures of normal human kidney proximal tubule ... epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids ...
| Abstract | The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury (AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters (SLC34A3 and cubilin). They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike (S) protein was able to enter CR cells with luciferase reporter. This integrated 2D CR and 3D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation. |
|---|---|
| MeSH term(s) | Angiotensin-Converting Enzyme 2 ; Animals ; Betacoronavirus/metabolism ; Betacoronavirus/pathogenicity ; COVID-19 ; Cell Culture Techniques/methods ; Cell Line ; Coronavirus/metabolism ; Coronavirus/pathogenicity ; Coronavirus Infections/virology ; DNA Damage ; Disease Models, Animal ; Epithelial Cells/virology ; Humans ; Kidney/virology ; Organoids ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/virology ; Receptors, Cell Surface/metabolism ; SARS Virus/metabolism ; SARS Virus/pathogenicity ; SARS-CoV-2 ; Sodium-Phosphate Cotransporter Proteins, Type IIc/metabolism ; Spike Glycoprotein, Coronavirus/metabolism |
| Chemical Substances | Receptors, Cell Surface ; SLC34A3 protein, human ; Sodium-Phosphate Cotransporter Proteins, Type IIc ; Spike Glycoprotein, Coronavirus ; intrinsic factor-cobalamin receptor ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-06-29 |
| Publishing country | China |
| Document type | Journal Article |
| ZDB-ID | 1011219-4 |
| ISSN | 1995-820X ; 1000-3223 ; 1003-5125 |
| ISSN (online) | 1995-820X |
| ISSN | 1000-3223 ; 1003-5125 |
| DOI | 10.1007/s12250-020-00253-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 4175: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.