Globally, acute or chronic lung diseases remain the leading cause of death, and their numbers are still rising. Conditions like Asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and idiopathic pulmonary fibrosis (IPF) affect hundreds of millions of people. COPD affects >500 million people around the world, and ARDS has a mortality rate of up to 40%.
Despite advances in treatment, current medications such as corticosteroids, bronchodilators, and anti-inflammatory drugs primarily manage symptoms rather than reversing damage. Researchers are now looking at mesenchymal stem cells (MSCs), a type of adult stem cell that has strong anti-inflammatory and tissue-regenerative properties, as a possible breakthrough in respiratory medicine.
Laboratory and animal studies have produced encouraging results in recent years. In models of acute lung injury (ALI), MSC therapy demonstrated the following:
- Lower pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) by > 40%.
- Raise the levels of anti-inflammatory cytokines like IL-10 that help the body to repair itself.
- Cut neutrophil infiltration by almost half to lower oxidative stress and protect fragile lung tissue.
In asthma models, MSCs reduced the levels of eosinophils in airway tissue by about 60%, which helped with airway hyperreactivity and inflammation. In studies of pulmonary fibrosis, MSC treatment decreased fibrotic mediators like TGF-β and IL-13, making the lungs more flexible overall. Animal studies also demonstrated significant survival advantages, with MSC-treated groups exhibiting 25–30% higher survival rates relative to untreated controls.
In addition to innate immunity, MSCs exhibited effects on adaptive immune responses. In experimental models, MSCs reduced IL-17 levels by nearly 50% and stimulated an increase in regulatory T cells (Tregs) characterized by elevated Foxp3 expression. This change in the Th17/Treg ratio was linked to less damage to the lungs and faster healing.
The unique ability of MSCs to interact with both innate and adaptive immune cells is central to their potential. Neutrophils, for example, are crucial in defending against infection but can cause severe lung damage when overactivated. It’s not only dampened their activity but also converts them into less harmful “senescent” forms. Similarly, MSCs influence macrophage immune cells, which can either damage (M1) or repair (M2) tissue by promoting a switch to the M2, tissue-healing state.
“MSCs are remarkable because they don’t just suppress inflammation; they actively restore balance in the immune system,” researchers noted in recent reviews. “That dual role is what makes them so attractive for treating complex lung diseases.”
Despite encouraging experimental results, large-scale clinical application remains limited. Most trials are in phase I/II, focusing mainly on severe COVID-19 complications and ARDS, but no phase III trials have been completed.
The heterogeneity of MSCs is a significant obstacle, where cells derived from various tissues, such as bone marrow, umbilical cord, or adipose tissue, exhibit differences in efficacy. Even MSCs from the same source can vary based on the age of the donor and how the lab prepared them. Therapeutic MSCs are usually used between the third and seventh cell passage because they lose their strength after that.
Safety concerns also persist. Risks include immune rejection, low survival rates after transplantation, and, in rare cases, complications such as pulmonary embolism reported in one early trial. Since MSCs are capable of self-renewal, questions remain about their long-term safety, particularly the possibility of contributing to tumor growth.
To overcome these barriers, researchers are also exploring MSC-derived extracellular vesicles (EVs) to show similar therapeutic effects without the same risks. EVs have better stability, higher compatibility, and no evidence of carcinogenic potential. However, large-scale production and standardized storage remain unresolved challenges.
Experts agree that more basic science and large-scale clinical studies are needed before MSCs can move from the laboratory to widespread medical practice. People with COPD, asthma, IPF, or ARDS must keep using conventional therapies. But the idea of a regenerative treatment that not only eases symptoms but also treats lung tissue gives people new hope.
In regenerative medicine for lung diseases, MSCs are one of the most exciting new developments. The challenge is to ensure they are safe, meet standards, and function effectively in a clinical setting. They might transform care for millions of people worldwide if this is accomplished.
References: Feng Y, Lu J, Jiang J, et al. Mesenchymal stem cells for lung diseases: focus on immunomodulatory action. Cell Death Discov. 2025;11:52. doi:10.1038/s41420-025-02303-4
