Transplanting progenitor cells to the lungs of bronchiectasis patients is safe and appears to stabilize disease, with no worsening in lung and physical function for at least 48 weeks, findings from a small clinical trial show.
The study, “Application of autologous SOX9+ airway basal cells in patients with bronchiectasis,” was published in The Clinical Respiratory Journal.
People with bronchiectasis experience progressive inflammation, scarring, and dilation of the airway structures (bronchi) that conduct air to the lungs, resulting in airway obstruction and poorer mucus clearing. Such irreversible changes make it progressively more difficult for air to enter the lungs and for oxygen to reach vital organs.
Current treatment approaches address symptoms, reducing their severity and impact on patients’ lives. Yet, because the therapies do not treat the underlying cause of disease, most patients experience several flares throughout their lives.
Treating injured lung tissue with progenitor cells — which like stem cells can differentiate into other types of cells, but to more limited degrees — is a promising approach to correct the damaging mechanisms of bronchiectasis. One study found that transplanting a type of basal progenitor cells with the ability to differentiate into the cells of the bronchi and alveoli — tiny sacs in the lungs where air exchange takes place — repaired the dilation and thickening of airway structures in two bronchiectasis patients, while improving lung function.
Researchers at the First Affiliated Hospital of Third Military Medical University, in China, and Regend Therapeutics opened a Phase 1/2 trial (NCT02722642) in that country to continue studying how progenitor basal cells might benefit people with bronchiectasis. The trial is recruiting patients at its single site in that country.
Researchers reported findings from the first seven participants: three women and four men, ages 41 through 57.
Participants first underwent a bronchoscopy, a procedure in which a thin tube is passed through the nose into the airways. Collected cells were taken to the lab, where progenitor basal cells were isolated and expanded. Notably, such progenitor cells can be easily identified because they produce the SOX9 protein.
When the cells were ready for treatment, patients underwent a bronchoalveolar lavage, a method that can be used to clean excess mucus from the lungs and provide a clean surface for cells to adhere.
During follow-up, their lung health and physical capacities were examined. They also underwent chest imaging scans at 4, 12, 24, and 48 weeks after surgery. Heart, liver, and kidney function were also assessed.
Results showed that measures of lung health — including percentages of forced expiratory volume in one second (FEV1%), forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLco%) — did not significantly change over the 48 weeks of follow-up.
“We found that [lung function measures ] were improved at 4, 12, 24, and 48 weeks after cell transplantation, although the differences were not significant, suggesting that the effects of airway BC [basal cell] transplantation on patients with bronchiectasis were positive,” the researchers wrote.
The percentage of predicted value for some of these measures — a calculation that accounts for a patient’s age and height — had improved at all follow-up examinations. Specifically, FEV1% of predicted value was significantly better after 48 weeks.
CT scans also showed that patients experienced no progression of bronchiectasis features, nor worsening in physical function or in overall health and symptom severity.
The transplant was also safe, with two patients experiencing inflammation or disease exacerbation after the procedure that were deemed related to bronchiectasis itself. No one died during follow-up, and all measures of blood cells, liver, kidney, and heart function were normal.
According to the team, the small group of people evaluated and the absence of a control patient group given standard treatment were among the study’s limitations. Longer follow-ups are also needed to confirm the safety and effectiveness of the approach, the researchers added.
“However, based on our results, transplantation of autologous SOX9+ BCs has positive effects and is safe in patients with bronchiectasis,” they concluded.