Advancing Mesenchymal Stem Cell Therapies for Bronchopulmonary Dysplasia: Challenges and Prospects

Bronchopulmonary dysplasia (BPD) is a critical lung pathology that primarily affects premature infants, particularly those who have been exposed to mechanical ventilation and oxygen therapy for extended periods. It causes disruption in lung development and increased risk for future respiratory problems. The pathophysiology of BPD involves inflammation and injury to the lung tissue, which leads to fibrosis, reduced alveolarization and impaired vascular growth. Traditional treatments for BPD focus on supportive care strategies to minimize lung injury and promote lung growth and administering medications to reduce inflammation. Despite advancements in trying to better understand the pathology of BPD, therapeutic interventions remain limited, which call for the need for novel and effective treatment strategies. A new comprehensive and expert opinion review published in the International Journal of Molecular Sciences and authored by Dr. Manuela Marega, Dr. Saverio Bellusci, Dr. Natalia El-Merhie and Dr. Cho-Ming Chao from the Justus Liebig University Giessen alongside Dr. Mira Y Gökyildirim from the University of Rostock and Dr. Valerie Orth from Witten/Herdecke University, the authors carefully analyzed all existing preclinical studies and clinical trials focusing on the use of mesenchymal stem cells (MSCs) and other stem/progenitor cells in  the treatment of BPD.

According to the authors, the etiology of BPD is multifactorial, encompassing pre- and postnatal factors that disrupt lung development and repair mechanisms. Preterm birth itself, by leading to an underdeveloped lung structure requiring mechanical ventilation and supplemental oxygen, sets the stage for hyperoxia-induced inflammation and subsequent abnormal lung development. The disease pathology is characterized by disrupted alveolarization, compromised microvasculature development, fibrosis, and cystic emphysema, driven by imbalances in signaling pathways. They examined existing treatments for BPD, including limited drug therapies like caffeine, vitamin A, and corticosteroids such as dexamethasone. Despite their usage, these treatments often offer limited therapeutic benefits and potential significant side effects, which highlights the need for better therapeutic strategies. This has necessitated the search for alternative therapies, with MSCs emerging as a promising therapeutic candidate due to their role in modulating immune responses and reducing inflammation.

A significant portion of the authors’ review focused on the therapeutic potential of MSCs. In recent years, the potential for using MSCs as a treatment for BPD has gained interest. The lung hosts various stem/progenitor cells, including basal cells, variant club cells, goblet cells, and alveolar progenitors, each playing a critical role in lung repair and regeneration. They discussed the anti-inflammatory effects of MSCs, their ability to secrete growth factors and cytokines, and their role in promoting tissue repair and regeneration. They emphasized on preclinical studies which indicated MSCs’ potential to contribute to lung injury repair. The mechanisms behind these effects are thought to include the reduction of inflammation, modulation of immune responses, and the promotion of tissue repair processes. Moreover, the review highlighted the importance of further understanding these cells’ biology, their interaction with cytokines and growth factors, and their potential therapeutic roles in treating BPD.

Additionally, the review also included an analysis of animal studies and clinical trials using stem cells or their secretome for BPD treatment. The mechanisms behind these effects are thought to include the reduction of inflammation, modulation of immune responses, and the promotion of tissue repair processes, however, more research is needed to fully understand these therapeutic mechanisms in greater detail. Moreover, there’s a critical need for developing standardized protocols for MSC therapy, including the optimization of cell preparation, dosage, administration timing, and long-term safety. Furthermore, significant knowledge gaps exist regarding the optimal use of MSCs in clinical settings, which necessitates more preclinical and clinical studies that could pave the way for MSC-based therapies in clinical settings. In conclusion, the authors’ expert review highlighted the potential of MSCs as a promising therapeutic option for BPD but also revealed the complexities and challenges that must be addressed first through further research and calls for a deeper understanding of stem cell behavior, the development of standardized therapeutic protocols, and a thorough evaluation of the long-term safety and efficacy of these interventions which ultimately will improve the quality of life for affected infants.