JAN 12, 2021 6:00 AM PST

Killer Control: Engineered Stem Cells Dodge Transplant Rejection

WRITTEN BY: Tara Fernandez

The first organ transplant—performed over 60 years ago—was a success because the donor and recipient were identical twins. It’s much riskier for patients receiving tissues from an unrelated donor due to mismatched gene variants that encode for molecules that decorate the surface of cells known as the major histocompatibility complex (MHC). 

Foreign MHCs are perceived as a threat by the immune system, which immediately sets to work, destroying the transplanted tissue. To sidestep this response, patients who have received organ transplants have to take a lifelong course of immunosuppressant drugs. Pharmaceutically dampening immunity is far from ideal for these patients; the immune system is there to shield us from a constant barrage of pathogenic threats.

"As a cardiac surgeon, I would love to put myself out of business by being able to implant healthy cardiac cells to repair heart disease," explained Tobias Deuse, lead author in a recent study published in the Journal of Experimental Medicine, which explores novel solutions for these ongoing challenges in regenerative medicine.

"And there are tremendous hopes to one day have the ability to implant insulin-producing cells in patients with diabetes or to inject cancer patients with immune cells engineered to seek and destroy tumors,” added Deuse.

According to Deuse, evading immediate rejection of transplanted tissues by the immune system is the holy grail. 

Deuse and colleagues at UC San Francisco have identified a way to achieve this by leveraging the immunobiology of stem cells. Specifically, they have developed a method for disarming the immune system's natural killer (NK) cells. These NK cells strongly influence the rejection or tolerance of transplanted tissues—if activated after implantation of the donor tissue, they flood the body with a cocktail of chemokines and cytokines that orchestrate the immune response. Reigning in these NK responses is, therefore, a key part of keeping transplanted organs safe.

Their stem cell-based approach was inspired by work in growing so-called “hypoimmune” cells in the lab. These genetically-engineered cells have in-built elements to turn off immune checkpoints—the activation switches of the immune system. Hypoimmune cells are designed to express high levels of a protein called CD47, which disarms specific innate immune cells via the SIRPα immune checkpoint, lulling them into a sense of security. 

Interestingly, the team found that this mechanism was particularly effective for evading NK cells. A deeper dive revealed that NK cells start to express SIRPα after activation by cytokines as inflammation begins to ramp up.

The clinical significance of this discovery can not be understated, say regenerative medicine scientists. "NK cells have been a major barrier to the field's growing interest in developing universal cell therapy products that can be transplanted "off the shelf" without rejection, so these results are extremely promising," said Lewis Lanier, a world-renowned expert in NK cell biology.

 

Sources: Journal of Experimental Medicine, UCSF.

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
You May Also Like
SEP 20, 2020
Microbiology
Middle-Aged Adults Might Always be Susceptible to H3N2 Flu
SEP 20, 2020
Middle-Aged Adults Might Always be Susceptible to H3N2 Flu
People born in the late 1960s or 1970s might be perpetually susceptible to the H3N2 influenza virus, according to new re ...
OCT 29, 2020
Cell & Molecular Biology
How Does the Immune System Handle the Microbiome?
OCT 29, 2020
How Does the Immune System Handle the Microbiome?
The human body plays host to trillions of microbes, and many of them live in our gastrointestinal tract; these microorga ...
NOV 17, 2020
Immunology
6 Injections a Year Prevent HIV Infections
NOV 17, 2020
6 Injections a Year Prevent HIV Infections
Last year, around 1.7 million people became infected with HIV, with around half of these being women. Encouraging result ...
DEC 08, 2020
Immunology
Drug Targets Cold Tumors' Achilles Heel
DEC 08, 2020
Drug Targets Cold Tumors' Achilles Heel
Immunotherapies have emerged as a powerful treatment modality for cancer. They join chemotherapy, surgery, radiotherapy, ...
JAN 06, 2021
Immunology
Probiotic Boosters Are Lifesavers for Preterm Babies
JAN 06, 2021
Probiotic Boosters Are Lifesavers for Preterm Babies
When administered shortly after birth, a recent study has found that the supplementation combo of probiotics and prebiot ...
JAN 18, 2021
Immunology
Arthritis Drug Approved for Critically Ill COVID Patients
JAN 18, 2021
Arthritis Drug Approved for Critically Ill COVID Patients
Critically ill COVID patients in the U.K. may receive an arthritis drug after a study showed that treatment lowered mort ...
Loading Comments...