Mesenchymal Stem Cell-Derived Extracellular Vesicles for the Treatment of Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants. However, there is a lack of effective treatment. Mesenchymal stromal cells derived extracellular vesicles (MSC-EVs), as nano- and micron-sized heterogeneous vesicles secreted by MSCs, are the main medium for information exchange between MSCs and injured tissue and organ, playing an important role in repairing tissue and organ injury. EVs include exosomes, microvesicles and so on. They are rich with various proteins, nucleic acids, and lipids. Now, EVs are considered as a new way of cell-to-cell communication. EVs mainly induce regeneration and therapeutic effects in different tissues and organs through the biomolecules they carry. The surface membrane protein or loaded protein and nucleic acid molecules carried by EVs, can activate the signal transduction of target cells and regulate the biological behavior of target cells after binding and cell internalization. MSC-EVs can promote the development of pulmonary vessels and alveoli and reduce pulmonary hypertension (PH) and inflammation and play an important role in the repair of lung injury in BPD. The regeneration potential of MSC-EVs is mainly due to the regulation of cell proliferation, survival, migration, differentiation, angiogenesis, immunoregulation, anti-inflammatory, mitochondrial activity and oxidative stress. As a new type of cell-free therapy, MSC-EVs have non-immunogenic, and are small in size and go deep into most tissues. What’s more, it has good biological stability and can be modified and loaded with drugs of interest. Obviously, MSC-EVs have a good application prospect in the treatment of lung injury and BPD. However, there are still many challenges to make MSC-EVs really enter clinical application.

Umbilical cord blood exosomes from very preterm infants with bronchopulmonary dysplasia aggravate lung injury in mice

“…The exosomes secreted by these umbilical cord blood MSCs can regulate related diseases through miRNA, regulate proliferation and migration-related TGF-β signaling pathways 35 , and also regulate inflammation-related GSK3β/Wnt/β 36 and IL-6/STAT3 pathway 37 . Umbilical cord blood exosomes are primarily protective in lung disease 38 . Another study of ours also showed that exosomes derived from healthy term umbilical cord blood can alleviate hyperoxia-induced lung injury 39 .…”

The effect of bioactivity of airway epithelial cells using methacrylated gelatin scaffold loaded with exosomes derived from bone marrow mesenchymal stem cells

“…23 components of the proteome secreted by cells and play a crucial role in mediating intercellular communication. 24 Due to their smaller size, 25 favorable biostability, low immunogenicity, biocompatibility and potential of large-scale production, 22 our research focus on the impact of BMSC-Exos on ECs. In this study, they were extracted and purified for characterization, and further investigated for the potential mechanisms by which they exert their biological effects.…”

Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design

“…It dramatically influences the composition of their secretome, allowing for the production of disease-specific exosomes [ 209 ]. Accordingly, they may display anti-inflammatory [ 210 ], pro-angiogenic [ 211 ], anti-apoptotic, or anti-oxidative properties [ 212 ]. Cell-free therapies offer many advantages over cell-based therapies: a higher scale of production, a lesser risk of contamination with CMV and HSV, the possibility for long-term storage and easier transportation, and fewer ethical considerations [ 213 ].…”