In an unexpected fusion of plastic surgery and cancer treatment, researchers at UC San Francisco have developed a groundbreaking technique that uses engineered fat cells to starve tumors and prevent their growth. Drawing inspiration from liposuction and fat transfer procedures, this innovative approach could revolutionize cancer therapy by utilizing modified fat cells to deprive tumors of the nutrients they need to survive.

Using CRISPR gene-editing technology, the scientists transformed ordinary white fat cells into “beige” fat cells—cells that burn calories aggressively to generate heat. In their experiments, these engineered fat cells were implanted near tumors, much like how plastic surgeons transfer fat between different body areas. The result was remarkable: the beige fat cells consumed large amounts of nutrients, starving the tumor cells and impeding their growth, even when the fat cells were placed far from the tumor site.

This method builds on existing medical techniques, which could lead to a faster clinical transition for this novel cancer therapy. “We already routinely remove fat cells with liposuction and put them back via plastic surgery,” said Nadav Ahituv, PhD, senior author of the study and director of the UCSF Institute for Human Genetics. “These fat cells can be easily manipulated in the lab and safely placed back into the body, making them an attractive platform for cellular therapy, including for cancer.”

Ahituv and his team were inspired by studies that showed cold exposure could suppress cancer in mice, as the cold activated brown fat cells to burn nutrients and produce heat. However, cold therapy is not feasible for cancer patients with fragile health. So, the researchers focused on beige fat cells, hypothesizing that they could be engineered to burn enough calories, even without cold exposure, to deprive tumors of essential fuel.

The researchers used CRISPR to activate genes that are dormant in white fat cells but active in brown fat cells, aiming to find the genes that would transform the white fat cells into calorie-burning beige fat cells. The gene UCP1 proved crucial in this transformation.

To test their theory, the team grew UCP1-enhanced beige fat cells and cancer cells in separate compartments of a petri dish. The cancer cells, located below the fat cells, were forced to share nutrients with the beige fat cells above them. The results were striking—very few cancer cells survived as the beige fat cells consumed all available nutrients.

The team next tested their approach in a more realistic context by implanting fat organoids—coherent clumps of cells—near tumors in mice. The engineered beige fat cells successfully starved breast cancer, pancreatic cancer, and prostate cancer cells, even when the fat cells were placed far from the tumor site. In some cases, the implanted beige fat cells suppressed tumors in genetically predisposed mice.

The researchers also worked with Jennifer Rosenbluth, MD, PhD, a breast cancer specialist at UCSF, to test their method using breast cancer mastectomies. They modified fat from the same patients, grew it in the lab, and tested its effectiveness against the patient’s own breast cancer cells. The modified beige fat cells outcompeted the cancer cells both in petri dishes and in mouse models.

Adapting Fat Cells to Target Specific Cancer Needs

The team also engineered fat cells to target specific nutrients that certain cancers rely on. For example, they programmed fat cells to consume uridine, which pancreatic cancer cells use when glucose is scarce. The fat cells effectively outcompeted these cancer cells, opening the possibility of tailoring fat cells to target specific cancer types based on their dietary preferences.

Fat cells offer several advantages as a platform for cellular therapy. They are easy to obtain, grow well in the lab, and can be genetically engineered to carry out specific biological roles. Furthermore, they behave predictably once implanted, causing minimal disruption to the immune system. This makes fat cells an ideal candidate for treating a range of diseases.

Ahituv also envisions using engineered fat cells for other medical purposes, such as sensing glucose levels to release insulin for diabetes or absorbing excess iron in conditions like hemochromatosis. The potential applications of this technology extend far beyond cancer, suggesting that engineered fat cells could play a transformative role in treating a variety of diseases.

With their ability to target tumors even when located far from the fat cells, engineered fat cells may offer hope for treating hard-to-reach cancers like glioblastoma, which affects the brain. The possibilities for this technology are vast, making it a promising step toward revolutionizing cancer treatment and beyond.

By Impact Lab