Scientists have grown universal stem cells using CRISPR engineering

Human heart muscle cells derived from new universal stem cells

Scientists from the University of California, San Francisco for the first time have grown universal stem cells using CRISPR gene editing technology to produce pluripotent stem cells that can be transplanted into any patient without causing an immune response.

Pluripotent stem cells are cells that can become cells of any type that the body needs. Just over a decade ago, revolutionary progress showed how fully formed adult cells can efficiently turn into pluripotent stem cells. These induced pluripotent stem cells (iPSCs) promised to change regenerative medicine, but clinical applications were not successful.

“There are many problems with iPSC technology, but the biggest hurdles are quality control and reproducibility,” explains Tobias Dees, lead author of the new study. “We don’t know why some cells are more easily reprogrammed than others, but most scientists agree that we are not yet sure of their clinical application. Because of this, most of the individualized iPSC therapy trials were suspended. ”

When growing iPSC, scientists need to start a complex and time-consuming process, including collecting adult cells from each independent patient, in order to avoid an immune reaction during subsequent cell transplantation. The new study aims to develop a new process for growing universal iPSCs that can be used by any patient.

To do this, scientists used CRISPR to turn off two specific genes that produce proteins that signal that they are targets of the immune system. However, scientists have found that these turned off proteins still trigger the natural killer (NK) immune cells to attack. Another piece of the puzzle was obtained from the CD47 gene. Researchers have found that NK activity can be inhibited by overexpression of the CD47 gene in iPSC.

Through various animal trials, researchers have found that these new, universal iPSCs can be transplanted into mice that have different immune profiles without any immune response. Taking it one step further, the researchers used the new iPSCs to grow human heart cells, which they transplanted into humanized chimeric mice. Not only was there no immune response to them, the cells began to form the earliest beginnings of the heart muscle.

“This is the first time that we have grown engineering cells that can be transplanted and which can survive in any immunocompetent recipients without causing an immune response,” says Dis.

Although much work needs to be done to develop specific safe therapies, this progress lays the foundation for these therapies being much cheaper and, hopefully, much more effective. If these new cells are safe and beneficial for patients, they will eliminate the costly and burdensome process of personalizing future stem cell treatments.

“Our technology can benefit a wider range of people, and the cost is much lower than with any personalized approach,” says Dis. “We need to make our cells only once, and we get a line that can be used universally.”

University of California San Francisco