Stem cell therapy is often a "last resort" treatment for patients with end-stage heart failure. A new study, however, finds that the treatment could be more harmful than helpful if cardiac stem cells are involved.
Researchers found that using patients' own cardiac stem cells to repair damaged heart tissue may not only be ineffective, but that the stem cells may also develop inflammatory properties that cause further heart damage.
Study leader Prof. Jonathan Leor, of the Sackler Faculty of Medicine and Sheba Medical Center at Tel Aviv University in Israel, and colleagues recently reported their findings in the journal Circulation.
There is currently no cure for heart failure. In some cases, the condition can be managed through medication and lifestyle changes. For people with end-stage heart failure, however, there are limited treatment options.
Heart transplantation remains the primary treatment for end-stage heart failure, but there are not enough donor hearts to meet recipient needs. Figures from the Organ Transplantation and Procurement Network show that there are more than 3,900 patients in the U.S. waiting for a heart transplant. Last year, 3,191 heart transplants were performed.
One treatment that is gaining popularity among patients with end-stage heart failure is autologous stem cell therapy. This involves using the patient's own stem cells to promote the regeneration of heart muscle and blood vessel cells.
Stem cells may be derived from the patient's bone marrow or heart tissue. The new study, however, suggests that using the latter may do more harm than good.
Transplanted cardiac stem cells may cause inflammation
Prof. Leor and colleagues came to their findings by isolating stem cells derived from the cardiac tissue of mice that had left ventricular dysfunction caused by a heart attack.
The team then injected the stem cells back into the hearts of the mice and assessed how they affected heart remodeling and function, compared with a saline solution.
Instead of repairing the rodents' damaged heart tissue, the researchers found that the transplanted stem cells developed inflammatory properties, which may increase heart damage.
"We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury," explains Prof. Leor.
"Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle."
An increasing number of end-stage heart failure patients are turning to stem cell therapy as a "last resort," but the researchers believe that the treatment should be approached with caution.
"[...] our findings suggest that stem cells, like any drug, can have adverse effects. We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient."
Prof. Jonathan Leor
Restoring the reparative state of stem cells
While the findings may come as a blow for many heart failure patients, the study did uncover some information that could help to improve autologous stem cell therapy.
By studying stem cells derived from the heart tissue of mouse models and humans with heart disease, the team was able to identify the gene that causes the stem cells to develop inflammatory properties.
Furthermore, the researchers found that deleting this gene, called TLR4, can shift the stem cells back to a reparative state, a discovery that the team believes could be used to transform autologous stem cell therapy for patients with heart failure.
"Our findings determine the potential negative effects of inflammation on stem cell function as they're currently used," says Prof. Leor. "The use of autologous stem cells from patients with heart disease should be modified."