October 27, 2020

The Niche

Knoepfler lab stem cell blog

Weekly reads: organoids, COVID-19, CIRM & cool new pubs

Organoids are providing a novel avenue into the pathogenesis of COVID-19 and novel models for drug screening. A number of new preprints on respiratory organoids shed new light in this area. They were highlighted in a Nature newsy piece, Mini organs reveal how the coronavirus ravages the body.

It’s a challenge to study COVID-19 infections because just infecting 2D cultures of various respiratory cells in a dish doesn’t necessarily tell you all you need to know about what goes on in the patient.

While 3D organoids aren’t perfect, they are a big step above regular monolayer cultures and can include a complex array of cell types more like those in patients.

Human intestinal organoids infected with SARS-CoV-2 (white). Credit- Joep Beumer:Clevers group:Hubrecht Institute
Human intestinal organoids infected with SARS-CoV-2 (white). Image credit: Joep Beumer of the Clevers group at Hubrecht Institute.

Organoids and COVID-19

From the Nature piece:

“Kazuo Takayama, a stem-cell biologist at Kyoto University, Japan, and his colleagues have developed bronchial organoids with four distinct cell types, made from frozen cells from the outer bronchial layer, or epithelium. When his team infected the organoids with SARS-CoV-2, they found that the virus mainly targets stem cells that replenish cells in the epithelium known as basal cells, but did not easily enter protective, secretory ‘club cells’. The team, which posted its work on bioRxiv, now plans to study whether the virus can spread from basal cells to other cells.”

The actual preprint from Takayama’s team is entitled, “Generation of human bronchial organoids for SARS-CoV-2 research.

Lung organoids for screening drugs for COVID-19

Another preprint comes from a group led by Shuibing Chen, “Identification of Candidate COVID-19 Therapeutics using hPSC-derived Lung Organoids.” Here are some key passages on the model and conclusions:

“As primary SARS-CoV-2 infection is respiratory-based, we developed a lung organoid model using human pluripotent stem cells (hPSCs) that could be adapted for drug screens.

Together, these data demonstrate that hPSC-derived lung cells infected by SARS-CoV-2 can model human COVID-19 disease and provide a valuable resource to screen for FDA-approved drugs that might be repurposed and should be considered for COVID-19 clinical trials.”

A variety of other organoids including intestinal ones (pictured above) are also being used to model COVID-19 disease and SARS-CoV-2 infection.

Also from the Chen lab, there is a new Cell Stem Cell paper on COVID-19 that seems distinct from the preprint.

CIRM officially will go to voters on billions more funding

Switching gears, another big regenerative medicine development comes from CIRM. Those supporting a new ballot initiative to give the agency $5 billion plus more funding have documented enough signatures from us California voters to now officially go to a vote on the November ballot for a second round of billions in funding. David Jensen over at California Stem Cell Report has been on this story all along and now has the news of the ballot qualification. Here’s the official state announcement of the qualification.

Some notable pubs of the past week