UCLA stem cell research may lead to new cancer treatments- Los Angeles health

Significant research is ongoing at UCLA's Eli and Edythe Broad Center of Regenerative Medicineand Stem Cell Research. The center's latest breakthrough was the discovery that a unique protein,pleiotrophin, can promote recovery of bone marrow-derived stem cells and the blood system afterinjury. The findings may lead to improved curative treatments and procedures for cancer and bloodrelated-diseases. The study was published online in the Journal of Clinical Investigation onSeptember 24.

The study authors explain that hematopoietic stem cells (HSCs), which are the cells that produce redand white blood cells, have been examined to gain understanding the mechanisms whereby the bonemarrow microenvironment regulates self-renewal and repair of HSCs. The research conducted bysenior author Dr. John Chute, UCLA Professor of HSC Result 2015 Hematology/Oncology andRadiation Oncology, has advanced the theory that bone marrow endothelial cells (the cells that formthe lining of blood vessels) play a major role in HSC regeneration. He also suggested that, followinginjury or stress, the blood system might benefit from and be informed by activities in the bonemarrow that direct HSCs to initiate recovery.

The researchers demonstrated that pleiotrophin acts upon HSCs by binding to a receptor on the

stem cell and activating a pathway known as the RAS signaling pathway. After an injury, thisactivation of RAS signaling promotes the recovery of the stem cell and blood system. For the study,the investigators used mouse models to administer pleiotrophin after the rodents had received alethal dose of radiation. They found that the protein promoted blood stem cell growth and fasterblood system recovery. As a result, two HSC Result 2015 thirds of the micel survived. Theinvestigators also added a RAS inhibitor (a substance that binds to the RAS pathway and prevents itfrom functioning) to the treatment; they found that the inhibitor reversed the survival advantagecompletely.

"We have now discovered at least one of the mechanisms through which a blood vessel-derivedprotein instructs blood stem cells to regenerate, and this has been shown both in vitro and in vivo,"said Dr. Chute. "By modeling it for potential use in human patients, this opens the door fortherapeutic possibilities."

The authors note that, worldwide, millions of cancer patients currently receive some form ofchemotherapy or radiation therapy with the goal of curing their disease. Unfortunately, most of themwill suffer damage to the blood system as a result. Current treatment methods are cyclical (generallyrequiring a 30-day wait period between treatments) to allow the blood system time to heal andrepair. The researchers are currently working toward a Phase I clinical trial in which patientsundergoing bone marrow transplantation and patients receiving chemotherapy would receivepleiotrophin with the goal of accelerating the recovery of the blood system. "With this discovery, wehope to provide the basis for improving outcomes for patients with cancer or other blood-relateddiseases and who are undergoing highly toxic treatments," explained Dr. Chute.