Science

Landmark research creates “universal” stem cells using CRISPR gene editing

Human heart muscle cells derived from the new CRISPR-engineered "universal" stem cells
Human heart muscle cells derived from the new CRISPR-engineered "universal" stem cells
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Human heart muscle cells derived from the new CRISPR-engineered "universal" stem cells
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Human heart muscle cells derived from the new CRISPR-engineered "universal" stem cells

In an incredible milestone, scientists have for the first time created "universal" stem cells by using CRISPR gene-editing technology to produce pluripotent stem cells that can be transplanted into any patient without generating an immune system response.

Pluripotent stem cells are those incredible cells that have the ability to become any kind of cell that the body needs. A little over a decade ago a revolutionary advance demonstrated how fully-formed adult cells could be effectively converted into pluripotent stem cells. Called induced pluripotent stem cells (iPSCs), this advance promised to change the practice of regenerative medicine, but clinical treatments have been frustratingly slow to materialize.

"There are many issues with iPSC technology, but the biggest hurdles are quality control and reproducibility," explains Tobias Deuse, lead author on the new study. "We don't know what makes some cells amenable to reprogramming, but most scientists agree it can't yet be reliably done. Most approaches to individualized iPSC therapies have been abandoned because of this."

In order to create iPSCs currently, scientists have to embark upon a complicated and time-consuming process involving harvesting adult cells from every individual patient so as to avoid an immune response when the cells are subsequently transplanted back. The new research set out to develop a new process to create universal iPSCs that can be used by any patient.

To do this, the scientists used CRISPR to switch off two specific genes known to generate proteins that signal they are targets to the immune system. However, the scientists discovered that these missing proteins still triggered natural killer (NK) immune cells to attack. The other piece in the puzzle came from a gene called CD47. The researchers discovered that NK activity could be inhibited by over-expressing the CD47 gene in the iPSCs.

Across a variety of different animal tests the researchers discovered that these new, triple-engineered, "universal" iPSCs could be transplanted into mismatched mice without any immune rejection. Taking it one step further, the researchers used the new iPSCs to make human heart cells which they transplanted into humanized mouse models. Not only were the cells not rejected, but they went on to form the earliest stages of heart muscle.

"This is the first time anyone has engineered cells that can be universally transplanted and can survive in immunocompetent recipients without eliciting an immune response," says Deuse.

While a great deal more work needs to be done to establish specific iPSC treatments that are safe and effective in humans, this important advance lays the foundation for these treatments to be much cheaper, and hopefully more effective. If these new cells prove safe and useful in humans, they would remove the costly and onerous process of personalizing future stem cell treatments to each individual patient.

"Our technique can benefit a wider range of people with production costs that are far lower than any individualized approach," Deuse says. "We only need to manufacture our cells one time and we're left with a product that can be applied universally."

The new study was published in the journal Nature Biotechnology.

Source: UC San Francisco

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