Promising Genetically-Enhanced Stem Cell Therapy for Pulmonary Arterial Hypertension Discovered

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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A new study recently published in the journal Circulation Research revealed encouraging results in the world’s first clinical trial using a genetically-enhanced stem cell therapy for pulmonary arterial hypertension (PAH). The study is entitled “Endothelial NO-Synthase Gene-Enhanced Progenitor Cell Therapy for Pulmonary Arterial Hypertension: the PHACeT Trial,” and was led by researchers at the University Health Network and the Ottawa Hospital Research Institute in Canada.

PAH is a life-threatening condition characterized by the increase of blood pressure in the pulmonary arteries that supply blood to the lungs. PAH can lead to difficulties in breathing, right-sided heart failure and eventually death. Overall, patients with this disorder have a poor prognosis and currently available treatments only offer a modest improvement in symptoms without repairing the blood vessel damage to the lungs.

Cell-based therapies have shown promising results in the repair and regeneration of the lung microcirculation in experimental models of PAH. “Pulmonary arterial hypertension is a deadly and incurable disease that often strikes people in the prime of their life,” said the study’s senior author Dr. Duncan Stewart in a news release. “We desperately need new therapies for this disease, and regenerative medicine approaches have shown great promise in laboratory models and in clinical trials for other conditions.”

In the study, researchers conducted a phase 1 clinical trial called Pulmonary Hypertension And Cell-Therapy (PHACeT) to assess the tolerability of a genetically-enhanced stem cell therapy and its impact on the repair and regeneration of lung blood vessels in PAH.

The team harvested a specific type of white blood cell from seven patients with PAH who were refractory to PAH-specific therapies. The cells were cultured in the laboratory under specific settings to select for stem-like cells known as endothelial progenitor cells. These cells were genetically engineered in order to produce greater amounts of nitric oxide, a natural, powerful vasodilator that plays an important role in vascular repair and regeneration. These genetically enhanced cells were then administered as three doses on consecutive days through a pulmonary artery catheter into the same donor patient.

Researchers found that the therapy was overall well tolerated by the PAH patients. However, one patient with severe, end stage disease died one day after treatment. The team believes that this outcome was due to the patient’s declining condition prior to the cell treatment. Researchers also observed that patients had an improved blood flow in the lungs, increased exercise capacity and a better quality of life up to six months after the therapy. The team is however cautious with this positive outcome as no placebo group was included in this trial, so it is not possible to determine whether the overall health improvement was due to the cell-based therapy or psychological factors.

“This trial shows that genetically-enhanced stem cell therapy is a promising treatment approach for pulmonary arterial hypertension” concluded Dr. Stewart. “Although this is an important start, we will need to do larger studies to establish whether this therapy can produce important and durable benefits for people suffering from this challenging disease.”

Dr. Stewart is currently also involved in the world’s first clinical trial based on genetically-enhanced stem cell therapy for heart attack.