Pulmonary diseases remain a major global health burden, affecting millions of individuals and significantly reducing quality of life. Conditions such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and complications following lung transplantation often lead to progressive loss of lung function, frequent hospitalizations, and limited treatment options. In recent years, regenerative medicine—especially therapies using umbilical cord–derived mesenchymal stem cells (UC-MSCs)—has emerged as a potential avenue for addressing these conditions. Thailand, known for its advanced medical facilities and expertise in regenerative therapies, has become a regional hub for exploring and offering UC-MSC–based approaches for lung disorders.
Stem cell therapy aims to support lung repair and reduce the inflammatory and fibrotic processes that drive many pulmonary diseases. While this field is still developing, early research suggests that UC-MSCs may help mitigate tissue damage, regulate immune responses, and improve the overall environment within the lungs. These possibilities have prompted increasing interest in how stem cell therapy might complement or enhance conventional treatments.
Why UC-MSCs Are Being Studied for Lung Conditions
Mesenchymal stem cells are among the most widely investigated cell types in pulmonary research due to their unique biological properties. UC-MSCs, in particular, offer several advantages: they proliferate efficiently, carry a low risk of immune rejection, and produce a broad range of molecules that can support healing. Their therapeutic potential comes from several key mechanisms:
- Anti-inflammatory capabilities: UC-MSCs produce substances such as interleukin-10 and prostaglandin E₂, which help suppress excessive inflammation. Many lung diseases involve chronic or acute inflammatory responses that damage tissues. By calming these responses, UC-MSCs may help create a more stable environment for recovery.
- Secretion of reparative signals: These stem cells release growth factors such as hepatocyte growth factor and keratinocyte growth factor—molecules known to support cell survival, reduce tissue injury, and promote regeneration. These signals do not necessarily require stem cells to become lung cells themselves; instead, they stimulate the body’s own repair mechanisms.
- Migration to injured lung tissue: Another advantage of UC-MSCs is their ability to travel toward areas of injury. Chemical cues present in inflamed or damaged lungs help guide the cells to where they are needed, allowing them to concentrate repair signals in the most affected areas.
Together, these features make UC-MSCs a promising strategy for conditions where inflammation, scarring, and structural deterioration play central roles.
Clinical Trial Landscape and Early Human Studies
Safety and Initial Findings in IPF
Multiple Phase I and Ib trials have tested mesenchymal stem cells from various sources—including bone marrow, adipose tissue, placenta, and umbilical cord—in individuals with IPF. These cells have been delivered either intravenously or directly into the airways during bronchoscopy. Across these studies, MSC administration has generally been safe, with no major treatment-related complications reported.
Although efficacy data are preliminary, some studies noted slower-than-expected declines in breathing function, small improvements in symptoms, or stabilization of disease markers. In one study using intrabronchial adipose-derived stem cells, patients showed excellent survival over two years without severe adverse effects. Another early trial, known for testing different MSC doses, found that higher doses were linked to slower loss of lung capacity.
MSCs for ARDS
Acute Respiratory Distress Syndrome involves a sudden, intense inflammatory reaction throughout the lungs. In a Phase I trial that delivered MSCs intravenously to ARDS patients, the treatment was found to be safe and feasible. Larger and more definitive trials are needed, but early results support further exploration.
Lung Transplant Complications
Complications after lung transplantation, including ischemia–reperfusion injury, primary graft dysfunction, and chronic lung allograft dysfunction (CLAD), are significant challenges. MSCs delivered directly into donor lungs before transplantation or given to recipients afterward helped reduce inflammation and improve graft stability.
Small Phase I studies in humans receiving MSCs for CLAD have shown safety and hinted at slower declines in lung function. Phase II trials are now underway to examine longer-term outcomes.
Beyond MSCs: Other Emerging Cell and Cell-Free Approaches
In addition to MSCs, researchers are studying other cell types and related technologies:
- Very Small Embryonic-Like stem cells (VSELs): These rare cells have been investigated for their ability to differentiate into lung epithelial cells and may serve as indicators of COPD severity or exacerbation.
- Induced pluripotent stem cells–derived MSCs: These laboratory-created cells are being tested in transplant-related lung injury models to examine their potential for immune regulation.
- Cell-free therapies: Exosomes and extracellular vesicles derived from MSCs carry many of the beneficial molecules without introducing whole cells. These therapies may offer improved safety, reduced risk of unwanted cell behavior, and easier storage and transport.
Future Directions for Pulmonary Stem Cell Therapy
Several key steps are needed to advance the field:
• Development of biomarkers to identify which patients are most likely to respond
• Exploration of engineered or preconditioned MSCs to enhance their reparative effects
• Disease-specific optimization of dosage and delivery routes
• Expansion of cell-free therapies for potentially safer treatment options
These areas of research will help refine the role of UC-MSC therapy in respiratory medicine.
Conclusion
UC-MSC–based therapy represents a promising path forward for individuals with serious lung conditions such as IPF, COPD, ARDS, and post-transplant complications. By regulating inflammation, supporting tissue repair, and influencing immune responses, stem cells may complement traditional treatments that focus primarily on symptom control. Although early clinical trials have shown good safety profiles and modest early benefits, larger studies are needed before these therapies can be widely adopted. As research grows and techniques become more advanced, UC-MSC therapy may play an increasingly important role in the future of pulmonary care, bringing renewed hope to patients facing chronic and progressive lung diseases.