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Treated human stem cells transplanted into a laboratory animal. The cells have differentiated to produce proteins occurring in human pancreatic cells. Colours: pink for insulin, yellow for glucagon, blue for nuclear DNA. (Image Credit: Rocio Sartori Maldonado)

Cell therapies could help in the treatment of hereditary diseases, myocardial infarction and hundreds of other diseases. For many blood diseases, new cells can already be transplanted into human patients, and diabetes has also been treated by transplanting cells obtained through organ donation or, more recently, β-cells modified from the patient's own stem cells.

A risk associated with gene-edited cells is unintentional DNA mutations, including those that predispose patients to cancer. Moreover, the difference in tissue types makes it impossible to transfer cells simply from one person to another.

Cells that suit anyone, or immunologically invisible cells, as it were, have been created, but they too are associated with an increased risk of cancer. Over a decade ago,  a research group set out to develop cells where these problems could be avoided. Now, the group has succeeded in producing cells which cannot proliferate unaided and which cannot therefore turn into malignant cells.

The study was published in Molecular Therapy.

Almost all of our diseases are fundamentally caused by cellular dysfunction. One medical dream is to fight tissue damage, diseases or even aging with new healthy cells. This new study takes us a step closer to safe and novel cell therapies.

The researchers modified stem cells to divide only if they are supplemented with thymidine, one of the building blocks of DNA. The cells that have been subjected to this safety treatment cannot replicate their genome without the supplementary component vital for DNA synthesis. This precludes their proliferation. When the cells are differentiated for their various tasks, they cease to divide and no longer require the supplement. The innovation has been protected by the University's Helsinki Innovation services (HIS).

Initially, the researchers investigated whether cell growth can be regulated with an externally administered substance. Once successful, they examined whether the cells functioned normally.

They used stem cells to create insulin-producing β-cells that they then transplanted into laboratory animals. The cells regulated the blood glucose levels of the animals throughout the almost six-month experiment.
The cells are also able to differentiate into other tissue types as usual, and the researchers have not observed any differences in them other than their inability to proliferate without their say-so.
Stem cells are very primitive cells, as they have to be able to divide in abundance and develop in many different directions. They have potential for a range of purposes, but their primitive nature also poses a problem: What if some cells are not differentiated, but continue to grow in a primitive form? According to the scientists of the study, the research group's solution enables the efficient proliferation of cells during production, which can be halted at the desired time, such as following transplantation.
The solution also makes it possible to edit cells without fear of adverse effects of the editing itself. For example, cells can be made into something that the recipient's immune system does not recognize.
Previously, such cells would have been highly risky, as the immune system also monitors the onset of cancer. Now, that risk is very small or non-existent. Ideally, these cells could be turned into products suited to everyone and, when necessary, quickly deployed.

Rocio Sartori-Maldonado et al, Thymidylate synthase disruption to limit cell proliferation in cell therapies, Molecular Therapy (2024). DOI: 10.1016/j.ymthe.2024.06.014

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