Intestinal Epithelium and Age-Related Decline
The intestinal epithelium, a single layer of cells lining the intestine, is essential for digestion and gut health. This lining typically renews every three to five days. Aging and exposure to radiation, such as in cancer therapy, can disrupt this renewal process, potentially leading to increased inflammation and conditions like leaky gut syndrome.
CAR T-Cell Therapy for Intestinal Repair
Scientists at Cold Spring Harbor Laboratory (CSHL) have identified a method to stimulate intestinal repair using CAR T-cell therapy, an immunotherapy primarily known for its application in cancer treatment. This research aims to inform future clinical trials focused on improving intestinal health, particularly in individuals affected by age-related decline.
Targeting Senescent Cells
This work builds upon previous research from CSHL Assistant Professor Corina Amor Vegas, which focuses on cellular senescence. Senescent cells are cells that cease division but persist in the body, accumulating with age and being associated with various age-related conditions, including diabetes and dementia. Earlier studies by Amor Vegas's team engineered anti-uPAR CAR T cells to selectively remove senescent cells in mice, resulting in improved metabolic markers.
Researchers, including Amor Vegas, CSHL Assistant Professor Semir Beyaz, and graduate student Onur Eskiocak, investigated whether removing senescent cells could restore intestinal healing capacity. They administered CAR T cells directly to the intestines of both younger and older mice. The results indicated that treated mice demonstrated improved nutrient absorption, reduced inflammation, and faster epithelial regeneration following irritation or injury.
Protection Against Radiation-Induced Damage
Leaky gut syndrome is frequently observed in cancer patients undergoing pelvic or abdominal radiation therapy. To model this, mice were subjected to radiation that damaged their intestinal epithelial cells. Mice that received CAR T-cell treatment recovered more effectively than untreated mice. A single dose of CAR T-cell therapy was observed to support gut function for at least one year.
Evidence also suggested that anti-uPAR CAR T cells promoted regeneration in human intestinal and colorectal cells. While the precise biological mechanisms are undergoing further investigation, these findings indicate potential therapeutic applications. Beyaz commented on the broader significance of this research in understanding age-related healing processes.