COVID-19 Test Model and Platforms Made With Human Embryonic Stem Cell Lines (hESCs)

In a previous article, I documented seven mice models humanized with aborted baby organs or with human fetal tissue-derived hormones or antibodies specifically for use in testing COVID-19 vaccines or therapeutics.

I have since found several more sophisticated examples and am listing them in this article for easier reader access. The first is a testing platform of beating human heart muscle tissue derived from human embyronic stem cells. The second is human lung and colonic organoids derived from human embyronic stem cells and transplanted into humanized mice. The third is a combination of both.

Cambridge University's Testing Platform of Beating Heart Muscle Cells Derived from Human Embryonic Stem Cells

This example does not involve humanized mice but is a testing model of beating cardiomycytes (heart muscle cells) derived from human embryonic stem cells, called hESC-CMs. Researchers from Cambridge published a study on July 29, 2021 (Williams et al.) in which they detail how they used a testing platform of hESC-CMs to screen heart-protecting medicines for COVID-19 patients.

Human embryonic stem cell-derived cardiomyocytes were infected with SARS-CoV-2 and various drugs were tested on the cells to assess the efficacy of the inhibitors.

Screenshot from the Methods section of the Williams et al. paper:

Human embryonic stem cells from the H9 (WiCell) line were used. The H9 stem cell line was developed at the University of Wisconsin as described in a Science magazine article dated

6 November 1998, from thirty-six "fresh or frozen-thawed donated human embyros produced by IVF" (in-vitro fertilization).

H9 human embryonic stem cells were grown in colonies and differentiated into beating cardiomycytes using a process detailed in this scientific study.

Another stem cell line, the famous HEK293 human embyronic kidney stem cell line was used to develop the SARS-CoV2 pseudotyped virus, called a "pCG1-SARS-CoV-2 Δ19 D614G HA spike plasmid."

Screenshot from the Methods section:

Their conclusion after testing was that benztropine and DX600 are novel inhibitors of SARS-CoV-2 and could be useful in patients in whom vaccination is contraindicated.

Our results provide a platform that has passed proof-of-principle to generate high-quality data in preclinical studies to justify translational research in animal models of acute respiratory distress syndrome and the repurposing of current drugs for clinical trials.

Weill Cornell Medicine's hPSC-LO and hPSC-CO Humanized Mice Models Made With Four Human Embryonic Stem Cell Lines (Han et al.)

A team of researchers from Weill Cornell Medicine and Mount Sinai Hospital developed two novel models of humanized mice using five human embryonic stem cell lines. The first, the hPSC-LO, has human lung organoids, and the second, the hPSC-CO has human colonic organoids.

The purpose of the study, published 28 October 2020, (Han et al.) was to study the response of human lung and colonic tissue to SARS-COV2 infection and provide in vivo platforms to facilitate drug screening of COVID-19 therapeutics.

The authors describe how they generated the hPSC-LO (Lung Organoid) humanized mouse model:

Screenshot from the study:

They made colonic organoids from the HUES8 stem cell line using strategies described in two studies: Crespo et al. and Munea, J.O. et al.

The authors give a short description of how they generated the hPSC-CO mouse:

Humanized mice carrying hPSC-COs in vivo provide a unique platform for modeling COVID-19. In brief, hPSC-COs were transplanted under the kidney capsule of NSG mice (Fig. 2m).

Four human embyonic stem cell lines were used in the experiment. Three are identified here:

1) The RUES2 human embyronic stem cell line was derived from a frozen IVF-derived embryo (provided by WiCell). 2) The HI human embryonic cells (provided by WiCell). 3) HUES8 human embryonic stem cells (Harvard University)

In addition, the HEK293 human embryonic kidney stem cell line was also used.

Weill Cornell's COVID-19 hPSC-Derived Human Organoid Testing Platform Made with Six Human Embryonic Stem Cell Lines (Yang et al.)

A large group of researchers mostly from Weill Cornell Medicine used six human embryonic stem cells (hESCs) to create a testing platform to study SARS-COV2 infection in human cells and organoids.

The authors claimed that there is an urgent need to study the pathological effects of COVID-19 on various human organs so they propose to create various organs in an experimental laboratory platform using hPSCs (including those derived from human embryonic stem cells:

There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs).

They explain how they used human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) can be used to create functional human cells, tissues, and organoids.

In their experiment they derived pancreatic alpha and beta cells, liver organoids, cardiomyocytes, and dopaminergic neurons.

Screenshot from the study:

In one of the experiments they transplanted the pancreatic organoids into humanized mice:

Screenshot:

A graphic from the study illustrating the transplantation process:

Six human embryonic stem cell lines were used in the study:

Screenshot from the Methods section:

*The Vero E6 stem cell line is derived from kidneys of the African green monkey.