A little paper cut on your finger is much less serious than a heart attack, but in each case your blood mobilizes various types of cells to the problem site and produces new blood cells to replenish those lost. Specialized cells, called “hematopoietic stem cells,” produce the new blood cells. Scientists thought hematopoietic stem cells stayed in the bone marrow but recent research has revealed that they, too, travel to the problem site: to the heart if a heart attack is in progress, or to the brain in the case of a stroke. Why these cells leave the bone marrow, how they know where to go, and what they do when they reach their target is what Jennifer Gillette, PhD, will use her $300,000 American Heart Association grant to study over the next four years. Dr. Gillette is a UNM Assistant Professor of Pathology at the UNM Cancer Center and her work could lead not only to better heart disease responses but also to improved cancer therapies.
Hematopoietic stem cells can mature into any of the blood and immune cells that course through our vessels. They are the cells that resupply your blood when you donate it or lose it as the result of an accident. They are also the cells that leukemic patients now receive directly, rather than receiving a complete bone marrow transplant. So, while they can’t become a new heart muscle cell, they can become any type of new blood cell. But Dr. Gillette thinks they play a role in directing the creation of new blood vessels at the site of a crisis. She says, “we think these cells are recruited to the heart by the vascular endothelium. And by targeting those cells, the hematopoietic stem cells may increase angiogenesis to help overcome the hit that occurs during the heart attack.”
The vascular endothelium are the cells that line the inside of blood vessels. When these cells are damaged in the case of a heart attack, they can secrete chemicals called chemokines to attract hematopoietic stem cells. Says Dr. Gillette, “it’s sort of like a homing beacon in the blood. The hematopoietic stem cells just keep going closer and closer to where the increased concentration of the chemokine is.” Part of the work that Dr. Gillette’s grant supports will investigate the chemokine signals and how they attract hematopoietic stem cells.
Once at the crisis site, hematopoietic stem cells direct the healthy endothelial cells to build new blood vessels, like a team of first responders trying to get food and first aid to a stranded group of people when the road is out. Another part of the work Dr. Gillette’s grant supports looks at how hematopoietic stem cells signal to other cells. Human cells have developed myriad and sophisticated ways to communicate with each other. In the case of angiogenesis, the building of new blood vessels, the Gillette lab believes this signaling process may use “exosomes” which are tiny vesicles or pouches that contain signaling molecules. Once inside the receiving cell, the signaling molecules start a cascade of changes that alter the cell’s behavior. Dr. Gillette and her team will study which signaling molecules are involved in angiogenesis and which specific changes they induce.
“Ultimately,” says Dr. Gillette, “we want to use this system and the drug discovery core at UNM Cancer Center to look for molecules that would enhance targeting of these cells to an injured endothelium.” By enabling the hematopoietic stems cells to find the damaged endothelial cells faster and more accurately, she hopes to show that they will triage a crisis like a heart attack more effectively, reducing the long-term negative effects.
This work can apply to cancer, too. Dr. Gillette’s research could shed light on important aspects about how hematopoietic stem cells might become leukemic. And, her work could also benefit people with leukemia who receive hematopoietic stem cell transplants. “These are cells that we’re going to transplant back into a sick person with cancer,” she says. “So, while this grant is applied to the heart,” explains Dr. Gillette, “it could be applied to how we get these transplanted cells back into the bone marrow of a cancer patient more effectively and efficiently. Once in the bone marrow, hematopoietic stem cells can repopulate a leukemia patient with healthy cells, therefore improving the ability of these cells to find their way to the bone marrow is equally important for advancing transplantation therapies.”
About the Grant
The American Heart Association is supporting the research reported in this publication under Award Number 13SDG14630080, Principal Investigator: Gillette, Jennifer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Heart Association.
About the UNM Cancer Center
The UNM Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated cancer center in the state. One of just 67 NCI-designated cancer centers nationwide, the UNM Cancer Center is recognized for its scientific excellence, contributions to cancer research and delivery of medical advances to patients and their families. Annual federal and private funding of over $65 million supports the UNM Cancer Center’s research programs. The UNM Cancer Center treats more than 65 percent of the adults and virtually all of the children in New Mexico affected by cancer, from every county in the state. It is home to New Mexico’s largest team of board-certified oncology physicians and research scientists, representing every cancer specialty and hailing from prestigious institutions such as MD Anderson, Johns Hopkins and the Mayo Clinic. Through its partnership with Memorial Medical Center in Las Cruces, the UNM Cancer Center brings world-class cancer care to the southern part of the state; its collaborative clinical programs in Santa Fe and Farmington serve northern New Mexico. The UNM Cancer Center also supports several community outreach programs to make cancer screening, diagnosis and treatment available to every New Mexican. Learn more at www.cancer.unm.edu.