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Temple Research on Bone-Derived Stem Cells that Repair Heart Tissue Gains Interest

December 5, 2013

 

Temple Research on Bone-Derived Stem Cells that Repair Heart Tissue Gains Interest


The regeneration of human heart tissue using cell-based therapies could revolutionize treatments for heart attack and heart failure. But while most researchers have looked to embryonic stem cells or genetically modified cells to do the job, a team of scientists led by Steven R. Houser, PhD, FAHA, Director of the Cardiovascular Research Center at Temple University School of Medicine (TUSM), have looked instead to stem cells from cortical, or compact, bone.

 

They seem like improbable candidates, but in a study published earlier this year in the journal Circulation Research, Dr. Houser and colleagues demonstrated that cortical bone-derived stem cells (CBSCs) can heal the heart just as well as, or even better than, stem cells that reside naturally in the heart. The team's report was so groundbreaking that it now ranks among the journal's most downloaded and read papers, which led to an invited talk on the research by Dr. Houser at the American Heart Association's Scientific Sessions 2013 meeting held Nov. 16‒20 in Dallas, Texas.

 

“Ischemic heart disease is a serious problem in [the United States],” Dr. Houser explained. “It leaves a portion of the heart dead, but the heart doesn't repair itself well, so [patients] often live with poor quality of life and have a decreased duration of life. We're trying to do something that can help [those] people, to see if cell therapy can improve on the standard of care.”

 

Dr. Houser's team investigated the potential of CBSCs by first isolating the cells from the tibias of mice and growing the cells in the laboratory. They then injected the cells into the hearts of mice that had suffered heart attacks and observed the cells as they prompted the secretion of healing factors in the heart and differentiated into new blood vessel cells and new cardiac myocytes (heart muscle cells).

 

The ability of the cells to work in multiple ways—repairing the myocardium through paracrine effects (the secretion of healing factors) and replacing killed cells through differentiation into new cell types—was among the team's most pivotal findings. The combined effects of those activities led to key improvements in survival and heart function in mice following heart attack.

 

Other types of cells that have been explored for cell-based heart therapy, including induced-pluripotent stem (iPS) cells, in which skin or other mature cell types are genetically reprogrammed into a stem cell-like state, have produced similar effects in animal studies. However, according to Dr. Houser, embryonic stem cells, iPS cells, and other types of stem cells are difficult to control. “[Once injected into tissue], the cells will form a tumor, which is a real risk with stem cell work,” he said.

CBSCs, by contrast, occur naturally in human bone tissue, and they do not form tumors, so Dr. Houser anticipates that the drawbacks of using the cells in patients with heart disease will be minimal. To more thoroughly explore the safety and effectiveness of the cells, he plans next to conduct a proof-of-concept study in large animals. “If that study works, we'll move to early stage clinical trials in humans,” he said.

 

Clinical trials with stem cells traditionally are carried out in patients who are very ill, often having reached the final stages of disease. While Dr. Houser's team would likely need to begin with end-stage disease patients, his ultimate goal is to treat patients when they are in earlier disease stages, before they reach terminal illness. By treating patients early in the disease process, it may be possible to make long-term improvements in quality and duration of life.

 

CBSCs nonetheless remain controversial. “Most people believe that bone-derived cells improve heart function through paracrine effects but do not engraft into the heart [to give rise to new heart cells],” Dr. Houser said. “But [we're confident] that we have a cell that does engraft.” To resolve uncertainties, others in the field are now beginning to repeat his team's experiments.