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MSC microvesicles for the treatment of lung disease: a new paradigm for cell-free therapy
Konstantinos Sdrimas1, Stella Kourembanas
11 Division of Newborn Medicine, Boston Children's Hospital , Boston, Massachusetts.
Insights
Mesenchymal stem cells (MSCs) show promise for treating bronchopulmonary dysplasia (BPD), a chronic lung disease in infants. Future therapies may focus on MSC-derived microvesicles for improved treatment outcomes.
Area of Science:
- Neonatal Medicine
- Regenerative Medicine
- Pulmonology
Background:
- Bronchopulmonary dysplasia (BPD) is a significant complication of preterm birth, causing morbidity and mortality despite advances in neonatal care.
- Cell-based therapies, particularly mesenchymal stem cells (MSCs), are being investigated for various lung injuries, including BPD.
Purpose of the Study:
- To review the efficacy of MSC treatment in experimental models of lung injury, with a focus on BPD.
- To explore the role of the MSC secretome, specifically microvesicles, as potential therapeutic mediators.
Main Methods:
- Review of existing literature on MSC therapy for lung injury models.
- Analysis of studies investigating MSC mechanisms, including paracrine, immunomodulatory, and cytoprotective effects.
Main Results:
- MSC therapy has shown potential in experimental models of lung injury and BPD.
- The therapeutic effects of MSCs are primarily attributed to paracrine, immunomodulatory, and cytoprotective mechanisms.
Conclusions:
- While MSC therapy holds promise for BPD, it remains experimental, requiring further research into optimal transplantation conditions.
- MSC-derived microvesicles represent a promising avenue for future BPD therapies due to their role as key mediators.
Significance:
Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of infancy, is a major complication of preterm birth that, despite improvements in neonatal respiratory support and perinatal care, remains an important cause of morbidity and mortality, often with severe adverse neurodevelopmental sequelae. Even with major advances in our understanding of the pathogenesis of this disease, BPD remains essentially without adequate treatment.
Recent Advances:
Cell-based therapies arose as a promising treatment for acute and chronic lung injury in many experimental models of disease. Currently, more than 3000 human clinical trials employing cell therapy for the treatment of diverse diseases, including cardiac, neurologic, immune, and respiratory conditions, are ongoing or completed. Among the treatments, mesenchymal stem cells (MSCs) are the most studied and have been extensively tested in experimental models of BPD, pulmonary hypertension, pulmonary fibrosis, and acute lung injury.
Critical Issues:
Despite the promising potential, MSC therapy for human lung disease still remains at an experimental stage and optimal transplantation conditions need to be determined. Although the mechanism of MSC action can be manifold, accumulating evidence suggests a predominant paracrine, immunomodulatory, and cytoprotective effect.
Future Directions:
The current review summarizes the effect of MSC treatment in models of lung injury, including BPD, and focuses on the MSC secretome and, specifically, MSC-derived microvesicles as potential key mediators of therapeutic action that can be the focus of future therapies.
