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News — LOS ANGELES (April 24, 2025) -- Cedars-Sinai is a leading transplant center, with patient outcomes that consistently meet or exceed national averages. One continuing challenge, however, is the need to suppress transplant patients’ immune systems to prevent their bodies from rejecting the transplant. Genetic engineering to prevent rejection has long been viewed as the “holy grail” of transplantation, and recent scientific progress suggests this goal is in sight.

, who recently joined the  and the  at Cedars-Sinai, is a pioneer and leader in the development of “hypoimmune cells,” which are designed to thwart transplant rejection. Schrepfer authored a paper in the peer-reviewed journal  reviewing the progress and challenges in developing therapies where cells generated from one individual are transplanted to another. She sat down with the Cedars-Sinai Â鶹´«Ã½room to discuss this emerging technology.

How did you come to study stem cells?

I started my career in medicine in 2002, caring for heart and lung transplant recipients. Seeing patients die from rejection or severe complications from immunosuppression was frustrating to me and I decided to focus my career on developing strategies to overcome immune rejection without immunosuppressive drugs. Since organs are clusters of large amounts of cells, I focused on engineering individual cells, stem cells, as a first step.

What is your approach to creating hypoimmune stem cells?

My approach uses genetic engineering to make stem cells invisible to the immune system. Nature has a mechanism for this, and pregnancy is the classic example. Half of the cellular proteins in a developing fetus are inherited from the father and are foreign to the mother. The fetal cells use hypoimmune mechanisms to prevent attack by the mother’s immune system. Studying these mechanisms led me to devise our current strategy. Over the course of more than a decade, using genome editing, I have managed to engineer stem cells that are invisible to the immune system. The advantage of engineering hypoimmune stem cells is that when these stem cells proliferate and create new cells, the new cells are also hypoimmune.

Are you the first person to create hypoimmune stem cells?

I was the first to use the , and it is probably fair to say that the word “hypoimmune” came from me. I was the first to publish on this topic and am thrilled to now see it used by many teams—though they use different approaches. The cells they create evade immune detection, meaning the host immune system doesn’t recognize the cells as foreign and does not attack them. Other strategies, called immune tolerance, attempt to teach the body’s immune system to accept the donor cells as their own. Right now, these concepts are classed together, but I am hoping the field will recognize that these are different concepts.

Do your hypoimmune edits only work with certain cell types?

We can use these edits on any type of cell. The advantage of creating hypoimmune stem cells is that you then have unlimited supply, because they proliferate endlessly, and they can be differentiated into any cell type.

Have hypoimmune stem cells been successfully turned into other cell types?

In my preclinical work, we turned the cells into many different cell types, including heart muscle cells; smooth muscle cells, found in blood vessel walls; and endothelial cells, which form the inner lining of blood vessels. The exciting thing about being here at Cedars-Sinai is that we have all the technology and great teams ready to take that next step and turn these cells into many more cell types on a larger scale.

What are some possible clinical uses for cells created from hypoimmune stem cells?

Hypoimmune stem cells could be used in a variety of cell therapies now being developed to treat diseases such as ALS [amyotrophic lateral sclerosis], retinitis pigmentosa, diabetes mellitus and inflammatory bowel disease. Using hypoimmune stem cells will allow production of cell therapies in great quantities and make them available to more patients. Additional research is still needed in all of these areas, but we continue making progress.

What questions are you working to answer next?

My dream is to take this concept from hypoimmune cells to hypoimmune organs and overcome the solid organ transplant barrier. We have done  to prove the concept, but there is still a long way to go. If we can prove our method overcomes organ rejection in humans, that opens the door to addressing many different diseases. And because I began in organ transplantation, this would close the loop for me.

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