Old Stem Cells Get Boost with New Technique

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Atta Behfar, MD, PhD
As people age, their stem cells also age, diminishing their functionality. Many studies conducted to determine the efficacy of cardiac stem cell therapy have used donor cells from younger patients. These cells are healthy and readily adopt the cardiogenic phenotype in which researchers are interested. The problem with that approach, however, is that in clinical trials, researchers want to use patients’ stem cells, but they can’t expect to have similar results as with younger donor cells. The answer is to find a way to manipulate autologous cells so they regain their “youthful” function.

My colleagues and I undertook research that involved taking these “sick” stem cells from sick patients and finding a way for them to regain their efficacy to repair heart muscle. We presented the work at ACC10 and received a Young Investigator Award, and it has since been published in the Aug. 26 edition of the Journal of the American College of Cardiology.

Essentially, we took bone marrow-derived human mesenchymal stem cells (hMSC) from the sternum of patients undergoing CABG. Interestingly, we found a rare class of patients whose stem cells had maintained their reparative functions. We couldn’t identify any specific patient profile that would be predictive of who would and who would not have this rare phenotype, but the discovery guided us in finding a technique to make everyone’s cells work again.

We do not genetically alter the stem cells, a technique that can make it more difficult in the regulatory approval process. Our approach to cardiopoietic guidance is to use recombinant proteins—growth factors—in the culture medium. It’s an environment similar to that seen during embryonic cardiogenesis, when signaling molecules direct stem cells to become cardiac-specific.

The big piece of our work was taking patient cells that weren’t reparative and manipulating them before transplanting them back into our heart failure murine models and finding that this manipulation could actually reactivate all the repair functions of those cells—they turn into cardiac progenitor stem cells and reacquire their repair efficacy.

In the study, we found that transplantation of cardiopoietic stem cells produced superior functional and structural benefit over a one-year follow-up compared to cells that were not manipulated. Engraftment of cardiopoietic stem cells into infarcted hearts was associated with a significant increase in human-specific protein content, along with induction of myocardial cell cycle activity. We concluded that in the setting of ischemic cardiomyopathy, preemptive cardiopoietic guidance enhances the therapeutic benefit of transplanted hMSC.

The proprietary culturing technology has been licensed to the Belgian company Cardio3 BioSciences, which in early March announced that the first patient in a prospective, multi-center trial had been treated with the cardiopoietic stem cell therapy, branded C-Cure. The trial will randomize patients to C-Cure plus optimal standard therapy versus optimal standard therapy alone. The trial also will evaluate socio-economic implications of therapy.

I see cardiac stem cell therapy as an adjunct to optimal standard of care. In the case of acute MI, patients will be stented and stem cells will be used to further repair the damaged myocardium and/or protect vulnerable areas of the heart. We have already significantly improved morbidity and mortality of heart attack patients with faster door-to-balloon times, improved drug-eluting stents and better anticoagulant drugs. Stem cell therapy adds another layer of protection.

Treatment for congestive heart failure also has advanced, with the use of afterload reducers, beta blockers, diuretics and more to optimize the cardiac pump function. On top of this care, physicians could potentially deliver stem cells, which may help rejuvenate the heart and make a big impact on patient quality of life. 

That’s how I perceive the near-term future benefit of stem cell therapy. Longer term, probably a decade or so away, we will see cell therapy being used for the formation of tissues or whole organs.

Dr. Behfar is a cardiology fellow at the Mayo Clinic in Rochester, Minn.