Scientists from UCLA's Jonsson Comprehensive Cancer Center (JCCC) have shown for the first time how a unique protein found in human bone marrow can drive stem cells to repair our blood system after an injury. These groundbreaking findings provide a roadmap to make existing radiation and chemotherapy treatments more effective for patients with cancer and other blood-related diseases.
Led by Dr. John Chute, UCLA professor of hematology and radiation oncology and JCCC member, the nearly two-year study was published online ahead of print in the Journal of Clinical Investigation.
Millions of cancer patients worldwide currently receive some form of radiation therapy or chemotherapy in hopes of curing the disease, and most will suffer damage to the blood system as a result. Current therapeutic regimens are also cyclical (generally requiring a 30-day wait period between treatments) to allow the blood system time to heal and repair.
Hematopoietic stem cells (HSCs) are cells in our body that can change and become any other type of blood cell (such as red or white blood cells). Scientists have long used HSCs in the laboratory to study how the bone marrow in our body can regulate and instruct these blood stem cells to regenerate and repair themselves, and thus help our bodies to recover after an injury or stress (such as following radiation or chemotherapy).
In his prior research, Dr. Chute discovered that specific cells that make up the lining of blood vessels in our bone marrow (called endothelial cells) play a key role in telling HSCs how to renew and repair themselves. He further theorized that following an injury or stress to our body, the blood system as a whole will benefit as the activities and functions happening in our bone marrow directly drive HSCs to promote and accelerate recovery.
In this new study, Dr. Chute and colleagues built upon their research to specifically identify a new protein called pleiotrophin. They discovered that the protein binds to HSCs, and that it is this process that activates recovery of blood stem cells and our entire blood system.
Dr. Chute's team conducted experiments in mouse models to administer pleiotrophin after a normally lethal dose of radiation. Results showed that HSCs and the blood system recovered faster, and in two thirds of the cases the animal survived.
Additionally, Dr. Chute's team found in further testing that by doing the opposite and actually blocking pleiotrophin (thereby preventing it from functioning), the blood stem cells saw no advantage in recovery. This highly suggests that the protein is key in accelerating recovery of the blood system.
"We have now discovered the mechanism by which pleiotrophin can instruct blood stem cells to regenerate," said Dr. Chute. "By modeling it for potential use in human patients, this opens the door for tremendous therapeutic possibilities."
Dr. Chute and his team are currently pursuing a Phase I clinical trial, with the goal of accelerated recovery for patients undergoing all types of radiation and chemotherapy as well as lessened delays between treatments.
"With this discovery, we hope to provide the basis for improving outcomes for patients with cancer or other blood-related diseases and who are undergoing highly toxic treatments," said Dr. Chute.
This research was supported by funding from the National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute. Additional funding was provided by the UCLA Broad Stem Cell Research Center.