Help us: Donate
Follow us on:



Engineering Cells to Avoid Immune Detection in Transplants

This technique is designed to remove the risk of rejection.


Gene editing can make stem cells invisible to the immune system, making it possible to carry out cell therapy transplants without suppressing the patients’ immune response [1].

Help me help you

Cellular therapies involve transplanting cells into a patient to replace the activity of malfunctioning or damaged cells. For example, cardiomycetes could be transplanted to repair or restore heart function, and endothelial cell transplants could be used to treat vascular diseases. While these therapies hold exciting potential, rejection of the transplanted cells is a significant hurdle to their widespread use. Rejection can be overcome by immunosuppression or by growing custom cells using a sample from the patient, but both approaches have drawbacks.

Instead, scientists in the US and Germany are using immune engineering to develop universal cell products that could be used in all patients. The idea is to create stem cells that evade the immune system; these hypoimmune stem cells are then used to generate cells of the desired type that can be transplanted into any patient without the need for immunosuppression, since the cells won’t elicit an immune response.

Hidden helpers

To accomplish this, the researchers used CRISPR-Cas9 to knock out two genes involved in the major histocompatibility complex, which is used for self/non-self discrimination. They also increased the expression of a protein that acts as a “don’t eat me” signal to protect cells from macrophages. Together, these changes made the stem cells look less foreign and avoid clearance by macrophages.

The team then differentiated endothelial cells and cardiomycetes from the engineered stem cells, and they used these to treat three different diseases in mice. Cell therapy treatments using the hypoimmune cells were effective in rescuing hindlimbs from vascular blockage, preventing lung damage in an engineered mouse model, and maintaining heart function following a myocardial infarction. In all three cases, transplanted cells derived from ordinary stem cells, which hadn’t been engineered to evade the immune system, were not effective.

“We showed that immune-engineered hypoimmune cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals,” said Tobias Deuse of the University of California, San Francisco, in a press release.


The emerging field of regenerative cell therapy is still limited by the few cell types that can reliably be differentiated from pluripotent stem cells and by the immune hurdle of commercially scalable allogeneic cell therapeutics. Here, we show that gene-edited, immune-evasive cell grafts can survive and successfully treat diseases in immunocompetent, fully allogeneic recipients. Transplanted endothelial cells improved perfusion and increased the likelihood of limb preservation in mice with critical limb ischemia. Endothelial cell grafts transduced to express a transgene for alpha1-antitrypsin (A1AT) successfully restored physiologic A1AT serum levels in mice with genetic A1AT deficiency. This cell therapy prevented both structural and functional changes of emphysematous lung disease. A mixture of endothelial cells and cardiomyocytes was injected into infarcted mouse hearts, and both cell types orthotopically engrafted in the ischemic areas. Cell therapy led to an improvement in invasive hemodynamic heart failure parameters. Our study supports the development of hypoimmune, universal regenerative cell therapeutics for cost-effective treatments of major diseases.


This technology is still far from clinical application, but this is nevertheless an exciting first step. Immunosuppression poses obvious risks to a patient, and generating custom cells for transplant therapy is expensive, often prohibitively so. The development of universal donor cells that can be used as therapeutics could bring the cost down significantly, making cellular therapeutics available to many more patients in a much safer way.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

Castration Influences Growth and Median Lifespan in Mice

Research published in Aging Cell has discovered that castrated male mice show similarities to females in growth and lifespan [1]....

Michael Lustgarten Fights Back Against Microbes

Dr. Michael Lustgarten delivers a clear and enlightening exploration of the intricate relationship between microbial burden and aging in Microbial...

Stabilized Vitamin C Improves Brain Aging in Mice

Korean scientists publishing in Nature were able to increase the stability of vitamin C, a powerful antioxidant, using a short,...

Bryan Johnson Thinks AI Should Run Your Life

In this video, Bryan Johnson, founder and CEO of Blueprint, shared his ideas about the role of artificial intelligence (AI)...


[1] Deuse, T. Hypoimmune induced pluripotent stem cell–derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice. PNAS (2021), doi: 10.1073/pnas.2022091118

About the author

Sedeer el-Showk

Sedeer became a professional science writer after finishing a degree in biology. He also writes poetry and sff, and somehow juggles an ever-growing list of hobbies from programming to knitting to gardening. Eternal curiosity and good fortune have taken him to many parts of the world, but he’s settled in Helsinki, Finland for the moment. He hopes he’ll never stop learning new things.
  1. jimofoz
    July 15, 2021

    Repair Biotechnologies is using the same technology when creating their macrophages that can break down oxidised LDL in the plaques that build up in blood vessels in atherosclerosis.

    Reason, author of the blog, founded Repair Biotechnologies.

Write a comment:


Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.