Curing Sick Stem Cells via Gene Therapy

Repairing heart muscle following a heart attack by stimulating new blood vessels to grow and increase oxygen delivery is an important therapeutic approach in cardiovascular disease. This is being studied using gene and cell therapy approaches to stimulate blood vessel cells to divide. The potential for triggering stem cells (immature cells in the body which can develop into a number of different specific mature cell types in a process termed “differentiation”) to promote new blood vessel growth has been pursued actively in recent years. However, using immature stem cells is challenging as our understanding of how they develop into specific cell types is incomplete.

Another option is the use of “progenitor cells,” which are stem cell-like cells which can divide and generate new tissue, but which have already been “pushed” into becoming a specific cell type via a process termed “lineage commitment.” An “endothelial progenitor cell,” or “circulating angiogenic cell,” is a cell that circulates in the bloodstream to repair damaged blood vessels and potentially to help generate new vessels. These cells can be easily purified from the patient’s blood and cultured in the laboratory before being re-injected into the patient as a therapeutic approach.

Here, Dr. Michael Ward and colleagues have made an important finding regarding these cells. By isolating them from patients with cardiovascular disease and healthy subjects for comparison, they show that circulating angiogenic cells from patients are not fully functional, preventing them from forming new blood vessels. Since the cardiovascular disease patients are very sick, they also have unhealthy circulating angiogenic cells.

Dr. Ward and his colleagues were able to “cure” the unhealthy cells by isolating them from cardiovascular disease patients and performing gene therapy on them in the laboratory. This was achieved using a virus to permanently modify the cells with the therapeutic gene. Following gene therapy, the cells regained the capacity to function as therapeutic cells and were able to induce new blood vessel growth and improve blood delivery to tissues when injected into an animal model.

This gene therapy approach to improve the functioning of a cell therapy shows great potential for leading to new treatments in cardiovascular disease.