One of the challenges in respiratory research in general, and for COVID-19 related projects in particular, is to have access to relevant in vitro cell culture models. Human lung epithelium models are currently being tested as a platform for COVID-19 research and several cell types susceptible to SARS-CoV infection have already been identified. In this post, I’ll introduce lung primary cell models you may find useful, as well as other cell types that have been reported as involved in COVID-19 infections and the multiple severe associated syndromes.

Physiologically relevant cellular models

Access to readily available, cryopreserved, fully characterized and quality controlled primary epithelial lung cells will facilitate COVID-19 research. The selection below, from tebu-bio’s broad primary lung cells offer, focuses on passage 0 bronchial cell populations.

Bronchial epithelial cell population at Passage 0

Normal Human Bronchial Epithelial Cells at Passage 0

Proliferating Normal Human Bronchial Epithelial Cells cryopreserved at passage zero (cat.nr NhBE-P0; Novabiosis) constitute a perfect source for investigating the function and pathology of the respiratory system for drug discovery cell screening in 3D tissue models.

The cell composition consists of undifferentiated ciliated, non-ciliated, goblet, and basal cells. They are isolated from the bronchus at the bifurcation point to the fourth generation of bronchi.

Lung NhBE-P0 proliferating cells Novabiosis tebu-bio.png

Distributed by tebu-bio in Europe, NhBE-P0 cells have been characterized in Air/Liquid Interface culture (ALI) validated by immunofluorescence using protein markers for Cilia (acetylated tubulin), mucin (MUC5AC), and tight junctions (Zonula Occludens-1), and basal cells (cytokeratin-5).

These cells are guaranteed to have minimum population doublings of at least 20 (from P0 to P2) following the instructions and conditions provided.

Normal Human Small Airway Epithelial Cells (cat. nr NhSAE-P0), harvested at passage zero, can also serve for this purpose. They are isolated from the fifth generation of bronchi down to small airways near 1mm in diameter. The cell composition consists of undifferentiated ciliated, non-ciliated, goblet, and basal cells and have been characterized in Air/Liquid Interface culture (ALI) validated by immunofluorescence using protein markers for Cilia (acetylated tubulin), mucin (MUC5AC), and tight junctions (Zonula Occludens-1).

Tissue-specific Extracellular matrices

The tissue-specific ECMs described below have specifically been designed for lung tissues to be used in either 2D or 3D cell culture.

Derived from healthy, non-tumour associated tissues with regional specificity, these new ECMs contain many crucial components (complex ratio of collagens, laminins, glycoproteins, proteoglycans, proteins, growth factors…) for more physiological and relevant culture reproducing the native in-vivo microenvironment. These lung-specific ECMs enable more relevant cell culture data and are available as tissue-specific lung ECM coating (cat. nr MTSLG201) or Hydrogel (cat. nr. MTSLG101) More details regarding this product range can be found in this post.

Primary Human bronchial epithelial cells show robust expression of lung epithelial cell markers panKT (green) and Nkx2.1 on NativeCoat Lung ECM

Airway primary endothelial cells

Other cell types may be useful to decipher respiratory syndrome pathology, whether in human or animal models. Cell Applications, Inc , a GMP certified cell provider distributed by tebu-bio in Europe, has one of the broadest ranges of such primary cells on the market: human microvascular or artery lung endothelial cells or animal pulmonary artery endothelial cells.

Smooth muscle cells and Endothelial cells from GMP validated Manufacturer Cell Applications, Inc.

Intestinal and Kidney cells

In addition to the alveolar cells in the lungs, ACE2 expression has been reported in other organs, including the kidney and the gut. Whether robust ACE2 expression in these organs affects SARS-CoV-2 infectivity is still unknown. However, acute kidney injury and abdominal pain are the most commonly reported co-morbidities of COVID-19 (refer to this review article for references).

In a recent post, I highlighted the kidney models we have recently launched. They may be of interest in this context, together with our intestinal primary cells from all portions of the intestinal tract.

Study cytokine release on any of these cell models

A recent article in the Lancet reported accumulating evidence suggesting that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. My colleague Philippe has recently written a post on the various products and services we offer to study such events.

The “Cytokine storm” seen in these severe forms of SARS-CoV infection can be reproduced within in vitro cell cultures with human PBMCs available as fully-characterized catalogue items or from normal and diseased donors, specially selected among our multiple sources of ethical and fully compliant sources of Human Biological Sample (HBS) program.

Related primary cell types:

tebu-bio head offices and laboratories, near Paris (France)

We know that during these times of confinement, you may struggle to make your project move. Our contract laboratories near Paris are fully active and can take on your research project, from lung primary cells culture to cytokine release multiplex quantification.

Isabelle Nobiron, PhD
Written by Isabelle Nobiron, PhD
Isabelle is a Product Manager at tebu-bio, and also the company's ISO Quality Manager.