Cold Spring Harbor Laboratory researchers report that engineered anti-uPAR CAR T cells cleared senescence-linked cells in mice, improving intestinal regeneration, reducing inflammation and strengthening gut barrier function. The approach also aided recovery from radiation-related intestinal injury and showed regenerative signals in experiments using human intestinal and colorectal cells, raising the possibility of future clinical trials.
The intestinal epithelium — a thin, single layer of cells lining the intestine — is essential for digestion and overall gut health. In healthy conditions, it renews itself every three to five days. Researchers say aging and exposure to cancer radiation can disrupt this renewal process, slowing regeneration and potentially contributing to inflammation and conditions such as “leaky gut syndrome.”
Scientists at Cold Spring Harbor Laboratory (CSHL) reported a potential strategy to jump-start intestinal repair using CAR T-cell therapy, an immunotherapy best known for treating certain cancers. The work builds on earlier research led by CSHL Assistant Professor Corina Amor Vegas, whose lab studies cellular senescence — a state in which cells stop dividing but persist in tissues. Senescent cells have been linked to several age-associated conditions, including diabetes and dementia.
In the new study, Amor Vegas and colleagues used engineered immune cells known as anti-uPAR CAR T cells. These CAR T cells are designed to target the urokinase plasminogen activator receptor (uPAR), which the researchers describe as a marker associated with senescent cells. Amor Vegas partnered with CSHL Assistant Professor Semir Beyaz and graduate student Onur Eskiocak to test whether eliminating uPAR-positive cells could restore the intestine’s ability to heal.
The team delivered CAR T cells directly to the intestines of younger and older mice. Amor Vegas said the results were “really significant improvements,” including better nutrient absorption, reduced inflammation and faster regeneration of the epithelial lining after irritation or injury.
To model intestinal damage that can occur after pelvic or abdominal radiation therapy, the researchers exposed mice to radiation that injured intestinal epithelial cells. Mice treated with CAR T cells recovered more effectively than untreated animals, and the study reported that a single dose supported healthier gut function for at least one year.
The researchers also reported evidence from experiments using human intestinal and colorectal cells suggesting that anti-uPAR CAR T cells can encourage regenerative activity. The study’s authors said the underlying biological mechanisms are still being investigated. Beyaz described the findings as an early step toward understanding how to better promote healing in older people.
The findings were published in Nature Aging in 2025 in a paper titled “Anti-uPAR CAR T cells reverse and prevent aging-associated defects in intestinal regeneration and fitness.”
