Could Bone Stem Cells Cause Damaged Hearts to Repair Ischemic Tissue?

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Interventional cardiologists and cardiac surgeons are adept at re-perfusing patients suffering from myocardial infarctions in order to save as much heart tissue as possible. Yet current best practices achieve little in terms of treating heart tissue that has become ischemic and died as a result of a heart attack.

Temple’s Cardiovascular Research Center (CVRC) is exploring a novel regenerative medicine approach that utilizes bone stem cells—not to generate new myocyte cells but to direct the damaged heart to quickly repair itself after a heart attack by replacing dead cardiac myocytes.

The bone cell research is one of the main initiatives funded by a five-year, $11.6 million grant from the National Heart, Lung, and Blood Institute, initially awarded to the CVRC three years ago. The grant’s focus: to develop new approaches to prevent, slow or reverse damage to the heart after a heart attack.

CVRC researchers tested a variety of cells using a mouse model. They rejected embryonic stem cells for two reasons: “Embryonic stem cells have the potential to form tumors in the heart,” says Steven R. Houser, PhD, FAHA, CVRC Director, “and, once the cells ‘commit’ to becoming cardiac muscle cells and are injected, they do not do well in an already-damaged heart.”

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Cortical bone stem cells may work better than marrow- or cardiac-derived cells for repairing the heart; transdifferentiation and paracrine signaling are key mechanisms in improving cardiac function and survival with bone-derived stem cells.  

Instead, the CVRC has been investigating primitive bone progenitor cells that probably are the source of bone marrow. The technique, in which cortical bone stem cells from one animal are expanded and then injected into another animal’s damaged heart, is now being tested in pre-clinical, large animal studies. Because they are allogeneic (not native to the animal with the cardiac dysfunction) the cells usually die within a month.

“But our hypothesis is that, before these cells die, they secrete molecules that enhance repair of the non-functioning, scarred tissue,” says Houser, who is also the Senior Associate Dean of Research and the Vera J. Goodfriend Endowed Chair of Cardiovascular Research at the Lewis Katz School of Medicine at Temple University.

If proven, Houser believes the technique could have significant therapeutic implications: “Potentially, if a patient came into an emergency room with a heart attack, you could give them these cells while they were also receiving a stent or a bypass and hopefully induce something beneficial for their heart.”

He also believes the research could have implications for treating other ischemic tissue, including fingers, toes and limbs.

Potentially, if a patient came into an emergency room with a heart attack, you could give them these cells while they were also receiving a stent or a bypass and hopefully induce something beneficial for their heart.

Houser’s CVRC is one of four research centers associated with the Temple Heart & Vascular Institute that are working collaboratively on NIH-funded cardiovascular research, including basic science focused on mitochondrial proteins and translational studies in cardiovascular disease.