All-purpose cells boost drug testing

Local | Carain Yeung 21 Apr 2017

Drug treatment will be safer if mouse models with humanized livers are used, University of Hong Kong researchers said after confirming its effectiveness on patients with inherited high cholesterol.

The HKU team is the first to reprogram urine cells into "all-purpose" cells and liver cells, putting them in the mouse models.

Cardiovascular medicine chair professor Tse Hung-fat, who led the study, yesterday said there have been patients who suffer from liver failure or even die after taking medicines found to be safe in mice or rabbits, because the animals' biological mechanisms are different.

Human liver cells cannot be cultured in a dish and therefore Tse said mouse models with humanized livers are designed. Traditionally, the cells will have to be drawn through blood or biopsy or from skin.

His team is the first to use the non- invasive way of drawing cells from urine, reprogram them into pluripotent stem cells, which he said are all-purpose like stem cells in embryos.

These all-purpose cells are differentiated into liver cells, which are then put into the mice with immunodeficiency to humanize their livers.

To prove the effectiveness of the models, the team recruited patients with familial hypercholesterolemia - a hereditary disease with the patients carrying genes from one or both parents which make their blood lipids high.

Some patients have serious side effects to statin, a traditional drug for high blood cholesterol, while new biological treatment such as PCSK9 costs a fortune.

The mouse models are used to test the drug's effects, allowing the researchers to monitor the impact on other organs.

Ms Leung, 64, has high blood cholesterol and three of her five siblings also have it. She once suffered from heart problems in 2011.

The level of "bad blood cholesterol" measured in Leung and the mouse is both lowered by 60 percent after PCSK9 treatment. Although the model is proven effective, Tse said: "Making one model for one individual patient is very expensive and it is not worth it."

Each mouse model costs about HK$50,000 to HK$100,000, Tse said.

More than 90 percent of familial hypercholesterolemia is due to the same problem of LDL-receptor mutation, Tse said, which he said makes it cost- effective to create a model with it applicable to a large group of patients.

He revealed that this project took four years and costs HK$5 million.

His team hopes to develop rabbit models within two years, adding that rabbits live up to 10 years while mice only live for a year.

Rabbit models will allow researchers to look for long term impacts or even pave the way for future liver regeneration.

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