Cost-Effective Cell Engineering to Treat Major Diseases

Researchers at UC San Francisco have shown that gene-edited cellular therapeutics can be used to successfully treat cardiovascular and pulmonary diseases. In a proof-of-concept study, the researchers have demonstrated that stem cell engineering could permit treating major diseases while evading the immune system.

This cell therapy technology has been tested in laboratory mice. But it's potentially applicable to human health care. And it could permit developing less expensive therapeutic applications to treat diseases for which there are currently few viable options.

A paper is published in PNAS. It reports that the researchers used gene editing to create “universal stem cells” (named HIP cells) that are not recognized by the immune system. They can be used to make "universal cell therapeutics." This could eliminate the need to generate custom cell therapeutics using a blood sample from every individual patient. Personalization is costly but has been necessary in order to avoid immune responses.

"We showed that immune-engineered HIP cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals,” says research co-leader Tobias Deuse in a press release issued by UC San Francisco . “This immune evasion was maintained in diseased tissue and tissue with poor blood supply without the use of any immunosuppressive drugs."

Then the researchers transplanted specialized, immune-engineered HIP cells into laboratory mice. And they found that the cell therapeutics could alleviate peripheral artery disease in hindlimbs. They could prevent the development of lung disease in mice with alpha1-antitrypsin deficiency. And they could alleviate heart failure in mice after myocardial infarction.

It is expected that, in human patients, the new cell therapeutics could eventually treat three major diseases affecting different organ systems. Those are peripheral artery disease, chronic obstructive pulmonary disease from alpha1-antitrypsin deficiency, and heart failure. Heart disease is increasingly a global epidemic with more than 5.7 million patients in the United States alone and some 870,000 new cases annually.

Deuse explains that this technology would make the manufacturing of universal, high-quality cell therapeutics more cost effective. Therefore, it could allow future treatment of larger patient populations. And that could facilitate access for patients from underserved communities.

"In order for a therapeutic to have a broad impact, it needs to be affordable," says Deuse. "That's why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases."

The researchers plan to explore the potential of HIP cells for treating other endocrine and cardiovascular conditions. Deuse explains that, because of the novelty of the approach, a careful and measured introduction into clinical trials will be crucial. Once more is known about human safety, he says, it will be easier to estimate when treatments using HIP cells might be approved and available for patients.