Electron microscopy of fat organoids that were implanted to out-compete tumors. Image by Ahituv Lab
Liposuction and plastic surgery aren’t often mentioned in the same breath as cancer.
But they are the inspiration for a new approach to treating cancer that uses engineered fat cells to deprive tumors of nutrition.
Researchers at UC San Francisco used the gene editing technology CRISPR to turn ordinary white fat cells into “beige” fat cells, which voraciously consume calories to make heat.
Then, they implanted them near tumors the way plastic surgeons inject fat from one part of the body to plump up another. The fat cells scarfed up all the nutrients, starving most of the tumor cells to death. The approach even worked when the fat cells were implanted in mice far from the sites of their tumors.
Relying on common procedures like this could speed its use as a new form of cellular therapy.
“We already routinely remove fat cells with liposuction and put them back via plastic surgery,” said Nadav Ahituv, PhD, director of the UCSF Institute for Human Genetics and professor in the Department of Bioengineering and Therapeutic Sciences. He is the senior author of the paper, which appears Feb. 4 in Nature Biotechnology. “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.”
Clumps of energy-hungry beige fat cells, made from white fat cells taken via liposuction, ate up all excess nutrients and starved growing tumors in an animal model. The tumors shrank - even when the fat cells were implanted far from the tumor. Image by Ahituv Lab
Cold therapy sparks a new idea
Ahituv and his post-doc at the time, Hai Nguyen, PhD, were aware of studies that showed exposure to cold could suppress cancer in mice. One experiment even showed it could help a patient with non-Hodgkin lymphoma. Scientists concluded that the cancer cells were starving because the cold was activating brown fat cells, which use nutrients to produce heat.
But cold therapy isn’t a viable option for cancer patients with fragile health. So, Ahituv and Nguyen turned to the idea of using beige fat, wagering that they could engineer it to burn enough calories, even in the absence of cold, to deprive tumors of the fuel they needed to grow.