Breath of Life: Stem cell Therapy for COPD

The burden of COPD has been rising globally. With the irreversible damage to the tissue, patients are often left with the options of lung transplant or ventilators in the advanced stages. Their quality of life drastically declines. The current pharmacological drugs have limited effectiveness. Stem cell transplant has been emerging as a promising therapy for COPD. Stem cells have the potential to reduce lung damage and restore its normal physiological functioning.

Chronic Obstructive Pulmonary Disease (COPD)

COPD is marked by the irreversible destruction of lungs and severe obstruction of airways. It falls under two categories- emphysema and chronic bronchitis. In chronic bronchitis, triggers like cigarette smoke or particles stimulate the inflammation in the lungs. Prolonged inflammation causes mucosal cell proliferation, excessive mucus secretion, death of lung epithelial cells, and infiltration of immune cells into the tissue. Overall, they result in narrowing the airways. 

Emphysema adversely affects the alveolar cavity. The triggers induce the formation of reactive oxygen species that stimulate diverse pathways such as inflammation, mucus secretion, and alveolar cell death. Additionally, emphysema demonstrates an increase in matrix-degrading proteases and imbalance their ratio to anti-proteases. Elastin imparts elasticity to lungs for adequate breathing and is one of the components of the matrix. Matrix degradation results in loss of elasticity in lungs. Current medications reduce the severity of disease, but do not improve the function of lungs and mortality in the long term.

The Potential of Stem Cell Therapy

The current mainstream treatments cannot reverse the lung damage. Therefore, alternative therapies are the need of the time. Stem cells have the regeneration potential that can reverse the pulmonary damage. These cells employ a multidimensional strategy to treat COPD:

• Reduce the apoptosis of lung cells.

• Improve the structure of pulmonary tissue.

• Promote the proliferation of tissue cells.

• Stimulate the tissue repair.

• Induce the anti-inflammatory cytokines to decrease inflammation.

Effects of Mesenchymal Stem cells (MSCs)

Three kinds of stem cells- embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and MSCs, have been studied for stem cell therapeutics. The teratoma formation by ESCs and the lack of clinical-grade iPSCs have prompted the application of MSCs for treatments. They act on the diverse pathological mechanisms of COPD.

• They differentiate into Type I and II alveolar cells.

• They reduce the levels of apoptotic genes and increase the anti-apoptotic genes to enhance cell survival.

• They alleviate the levels of inflammatory cytokines interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α.

• They also augment the levels of anti-inflammatory cytokines like IL-10, transforming growth factor (TGF)-β.

• They reduce matrix-degrading proteases and balance the ratio of proteases to anti-proteases to maintain the extracellular matrix and elasticity.

• They decrease the oxidative stress that causes cell damage and inflammation.

Sources of MSCs

MSCs can be sourced from bone marrow, adipose tissue, and umbilical cord. Allogeneic or autologous transplantation is possible for bone marrow and adipose tissue-derived stem cells. During autologous transplantation, patients suffer from additional pain from stem cell extraction. Moreover, bone marrow comprises small quantities of MSCs (less than 0.1%). Research has revealed age-induced adverse effects in MSCs like increased senescence, shorter telomeres, low differentiation potential, and low proliferation capacity. In comparison, umbilical cord MSCs (UC-MSCs) have higher proliferation and differentiation ability. They can be extracted in large quantities, thus making UC-MSCs better candidates for stem cell therapy.

Clinical Studies

Studies in animals have shown positive results, such as improvement in lung function, decreased inflammation, increased proliferation of pulmonary cells, and protease inhibition. In humans, Weiss et al. conducted the trial with bone marrow MSCs (BM-MSCs). The four monthly administrations of BM-MSCs showed decreased levels of C-reactive protein, an inflammatory indicator. The study also proved that the transplant was completely safe in the patients without any signs of negative impact.

In the first study using UC-MSCs for COPD, stem cells were expanded in vitro and administered intravenously. This treatment also didn’t show any adverse complications arising from the transplant. The transplant significantly reduced the breathlessness, the impact of COPD on the patient's life, and the worsening of symptoms. It concluded that UC-MSCs can improve the quality of life in mild to severe COPD patients. Another study with four infusions at a 2-week interval demonstrated improved lung function.

Current Research

Most of the research has focused on MSCs derived from umbilical cord and adipose tissue. The UC-MSCs can be extracted in large quantities and have higher potential than that from other sources. UC-MSCs have shown positive outcomes, but the procedure needs to be streamlined. The dosage of stem cells, the number of infusions, the interval between infusions, and the route of administration require further investigation. The absence of any side effects of MSC administration has been optimistic. Further research in this direction can introduce MSC-based therapy as the mainstream COPD treatment.

Conclusion

COPD is projected to affect 600 million people by 2050. The current modalities do not show long-term improvements. Stem cell therapy holds tremendous potential in COPD treatment with their ability of regeneration, immunomodulation, repair, and paracrine signaling. Several clinical studies have suggested the effectiveness of MSC therapy and have proven their safety in humans. The future might witness the optimization of MSC therapy for COPD. Advancells, a premium manufacturer of stem cells in India, provides the quality-assured UC-MSCs with guaranteed purity and sterility.