Mesenchymal stromal/stem cells and bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, leading to chronic respiratory disease. There has been an improvement in perinatal care, but many infants still suffer from impaired branching morphogenesis, alveolarization, and pulmonary capillary formation, causing lung function impairments and BPD. There is an increased risk of respiratory infections, pulmonary hypertension, and neurodevelopmental delays in infants with BPD, all of which can lead to long-term morbidity and mortality. Unfortunately, treatment options for Bronchopulmonary dysplasia are limited. A growing body of evidence indicates that mesenchymal stromal/stem cells (MSCs) can treat various lung diseases in regenerative medicine. MSCs are multipotent cells that can differentiate into multiple cell types, including lung cells, and possess immunomodulatory, anti-inflammatory, antioxidative stress, and regenerative properties. MSCs are regulated by mitochondrial function, as well as oxidant stress responses. Maintaining mitochondrial homeostasis will likely be key for MSCs to stimulate proper lung development and regeneration in Bronchopulmonary dysplasia. In recent years, MSCs have demonstrated promising results in treating and preventing bronchopulmonary dysplasia. Studies have shown that MSC therapy can reduce inflammation, mitochondrial impairment, lung injury, and fibrosis. In light of this, MSCs have emerged as a potential therapeutic option for treating Bronchopulmonary dysplasia. The article explores the role of MSCs in lung development and disease, summarizes MSC therapy's effectiveness in treating Bronchopulmonary dysplasia, and delves into the mechanisms behind this treatment.

Keywords: bronchopulmonary dysplasia; development; extracellular vesicles; mitochondria; stem cells.

FIGURE 1

The role of mesenchymal stem cells in pulmonary development. During embryonic development, lung mesenchymal stem cells (MSCs) arise from the splanchnic mesoderm and subsequently differentiate into specialized mesenchymal lineages through paracrine signaling and mitochondrial regulation to coordinate key processes in lung morphogenesis, including airway branching, alveolarization, and vascular development.

FIGURE 2

MSC-EVs mediate therapeutic effects in BPD. MSCs predominantly promote lung repair in BPD through paracrine. MSCs release EVs containing bioactive molecules and mitochondria that mitigate injury. In addition, EV isolation offers the potential for cell-free treatment. MSC-EVs are enhanced in their regenerative capacity by pre-conditioning, bioengineering, and genetic modification in vitro. Optimizing EV production and delivery to maximize lung localization may enable clinical translation for treating BPD.