Regenerative Medicine as an Option for Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Affecting an estimated 15 million people in the United States alone, COPD is characterized by progressively worsening symptoms, including breathing difficulty, cough, mucus (sputum) production, and wheezing, and is most often the result of prolonged exposure to cigarette smoke.

Not just an issue for those in the U.S., COPD has been demonstrated to be a preventable and treatable global health challenge. With an estimated 3.5 million worldwide deaths attributed to COPD each year, the disease is currently the third leading cause of death.

While there have been medical advances in the treatment of COPD, these therapies focus primarily on symptomatic relief and not the reversal of lung function deterioration or improvement in patients’ quality of life.

Since stem cells are known to differentiate into a wide variety of cell types and have been previously used to regenerate lung parenchyma and airway structure, they are believed to be an evolving and promising therapeutic treatment option for those with COPD.

Supported by extensive studies exploring the mechanism of stem cells in the regulation of COPD, experts have demonstrated that stem cells possess multidirectional differentiation potential and are able to differentiate into specific forms of alveolar epithelial cells (type I and/or type II) and participate into the repair of lung tissue structure.

In this review, Chen et al. summarize the most relevant findings of eight clinical trials that explore the treatment of COPD with mesenchymal stem cells (MSCs). 

These clinical trials, conducted between the years of 2009 – 2020, examined using different modes and doses of a variety of autologous or allogeneic MSCs, including bone marrow-derived stem cells (BM-MSCs), adipose tissue-derived stem cells (AD-MSCs), and umbilical cord-derived stem cells (UC-MSCs), in the treatment of COPD.

Examining the different types of MSCs used for these clinical trials, the authors conclude that while all types of MSCs have benefits in this application, AD-MSCs and UC-MSCs are very promising, primarily because the source is easily available; additionally, the process of collecting UC-MSCs is non-invasive. Looking at trends in recent clinical trials, the authors find a general increase in the shift toward using AD-MSCS and UC-MSCs and away from BM-MSCs, primarily for the reasons mentioned previously.

Analyzing results of these clinical trials related to mode, schedule, and dosage of administration, the authors found that stem cells administered intravenously into the body concentrated in the lungs for thirty minutes before gradually migrating to the liver; the inability of stem cells to keep stem cells in the lungs for a longer period of time was noted as a potential barrier that could limit the effectiveness of stem cell therapy for this condition.  

To address this concern, the authors recommend adjusting the schedule and/or mode of administration, indicating that prior research suggests multiple doses and administration via airway injection using a bronchoscope is a good way to deliver stem cells directly to the lungs. 

Chen et al. found that regardless of what type of MSCs and what mode of administration was used, stem cell therapy for the management of COPD has been proven to be safe and without evidence of any adverse events. However, only 2 of the eight clinical trials evaluated for this review demonstrated that MSCs could improve pulmonary function. The results of the other six indicated that MSCs had no effect on pulmonary function. 

Considering these findings, and in view of the small number of patients in the two clinical trials demonstrating therapeutic improvement on pulmonary function, the authors call for further research to better understand the effects of MSCs on improvements of pulmonary function.  

In closing, Chen et al. indicate that stem cell therapy may have a significant role in the future treatment of COPD and other respiratory diseases and offer a number of suggestions for future clinical trials. The recommendations provided by the authors for future clinical trials examining the therapeutic effects of MSCs when treating COPD include expanding the sample size, extending the follow-up time to a minimum of 2 years, selecting patients with different grades of COPD, considering using AD-MSCs and UC-MSCs (rather than BM-MSCs); and further exploring the effects of MSC on change in other inflammatory, immune, and metabolic indicators.  

Source: “Stem cell therapy for chronic obstructive pulmonary disease – PMC.” 15 Jun. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280064/.