Life depends on a single breath—but once you develop COPD, taking a deep, effortless inhale becomes harder than reaching for the stars. Imagine being buried alive, with dirt already pressing against your throat; or picture yourself climbing a mountain, only to feel as though something—a lump of blood, perhaps—has lodged painfully in your windpipe. These are the very real experiences of people living with chronic obstructive pulmonary disease.

Based on current research, mesenchymal stem cells primarily exert their effects on pulmonary fibrosis and chronic obstructive pulmonary disease through five key mechanisms.

Figure 2: Effects and Mechanisms of Mesenchymal Stem Cell Transplantation in Treating Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis.

Telomere Regulation: Lung diseases are associated with telomere alterations, and research shows that patients with idiopathic pulmonary fibrosis can reduce telomere shortening—and improve their condition—through treatment with mesenchymal stem cells. ^[12-13] Mesenchymal stem cells may slow the progression of lung diseases and improve lung function by reducing telomere attrition in alveolar epithelial cells, fibroblasts, and other cell types.

Reducing oxidative stress: Gradually increasing oxidative stress during the aging process is a key factor contributing to lung diseases. By alleviating oxidative stress, it’s possible to improve age-related deterioration of lung tissue, reduce the incidence of lung diseases, and slow the progression of chronic lung conditions. Research has shown that mesenchymal stem cells effectively mitigate excessive oxidative stress in tissues. Reactive oxygen species are byproducts generated when cells metabolize oxygen, and they are closely linked to oxidative stress.

Liu et al. ^[13] It was discovered that bone marrow mesenchymal stem cells can effectively reduce reactive oxygen species in lung tissue of rats with lung injury, thereby alleviating pulmonary damage. Huang et al. ^[14] Research has found that implanting bone marrow mesenchymal stem cells significantly increased superoxide dismutase activity and total antioxidant capacity in the lung tissue of a mouse model with pulmonary fibrosis, suggesting that mesenchymal stem cells can alleviate oxidative stress in lung tissue. Additionally, malondialdehyde and heme oxygenase-1 are two substances with opposing effects: while the former enhances oxidative stress, the latter exerts antioxidant and cytoprotective functions. Fredenblibgh et al. ^[15] It was discovered that mesenchymal stem cells can reduce pulmonary malondialdehyde levels while simultaneously increasing heme oxygenase-1 synthesis.

Replenishing depleted stem cells, modulating relevant molecules, and improving cellular apoptosis and aging to repair lung tissue: Mesenchymal stem cells can serve as a supplement to already exhausted stem cells, offering anti-apoptotic effects that may help treat pulmonary fibrosis and chronic obstructive pulmonary disease. Currently, it has been reported that bone marrow-derived mesenchymal stem cells can differentiate into alveolar epithelial cells both in vivo and in vitro, and they are capable of successfully engrafting in the lungs. For instance, Huang et al. ^[16] It was found that intravenous implantation of bone marrow mesenchymal stem cells can reduce the severity of pulmonary fibrosis in rats and enable these cells to engraft in the lungs of the animal model, where they differentiate into type II alveolar epithelial cells. Liu et al. ^[17] It was found that human umbilical cord mesenchymal stem cells transplanted into a mouse model of lung injury effectively suppress cellular senescence and apoptosis, with mesenchymal stem cells successfully engrafting in the lung tissue. Additionally, these mesenchymal stem cells can secrete various factors at specific sites to inhibit tissue degeneration and promote lung repair, as shown in Figure 3.

Figure 3: Mesenchymal stem cells secrete cytokines in the lungs. These cells release hepatocyte growth factor and vascular endothelial growth factor in the lung, promoting the repair of pulmonary damage.

Regulating pulmonary immunity: Lung diseases are closely linked to diminished systemic immunity and immune dysregulation. The low immunogenicity and immunomodulatory properties of mesenchymal stem cells have been widely recognized. ^[18] Gupta et al. ^[19] Proof shows that mesenchymal stem cell transplantation reduces the levels of the pro-inflammatory cytokine TNF-α in bronchoalveolar lavage fluid of mice with chronic obstructive pulmonary disease, while simultaneously increasing the anti-inflammatory cytokine IL-10. Additionally, it effectively ameliorates lung injury induced by endotoxin. Similarly, Li et al. ^[20] It was also reported that mesenchymal stem cells significantly suppress lung inflammation in mice with pulmonary fibrosis and can even improve the extent of fibrosis. Jackson et al. ^[21] Researchers have discovered that mesenchymal stem cells can transfer their own mitochondria into macrophages via tunneling nanotube-like structures, thereby modulating macrophage function and enhancing their ability to engulf bacteria, as shown in Figure 4.

Regulating the extracellular matrix: In lung diseases, the extracellular matrix undergoes significant alterations. Several studies have now demonstrated that mesenchymal stem cells can act as regulatory agents, helping to reverse the pathological changes in the extracellular matrix. Moodley et al. ^[22] In mice that developed pulmonary fibrosis due to bleomycin, collagen deposition can be modulated by mesenchymal stem cells. Meanwhile, Fikry and colleagues ^[23] Evidence was found of reduced collagen deposition in a rat model of pulmonary fibrosis treated with mesenchymal stem cells. Additionally, mesenchymal stem cells can reverse the expression of matrix metalloproteinase-9 and matrix metalloproteinase-12 by decreasing trypsin activity, thereby modulating extracellular matrix changes in lung tissues of a chronic obstructive pulmonary disease model, alleviating emphysema lesions, and improving lung function. ^[24] 。