Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Type II Cell Proliferation and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia

Abstract

Although it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide- (LPS-) induced BPD rat model and to clarify the underlying mechanism. We demonstrate that antenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature, which restored by hUCMSCs and MVs treatment. Furthermore, MVs were large vesicles with a diameter of 100-900 nanometers and mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, PTEN/AKT and MAPK pathways were associated with the protection of MVs. Taken together, this study suggests MVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuating lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

CREB1 Transcriptionally Activates LTBR to Promote the NF-κB Pathway and Apoptosis in Lung Epithelial Cells

“…ATII cells are pulmonary epithelial progenitor cells and exist in the corners of alveoli, taking up only 5% of alveolar surface area in healthy adults with many functions including synthesizing and secreting surfactants, transporting intrapulmonary fluid and ion, supporting immune modulation, and regenerating alveolar epithelium after injury [28]. Injury of ATII cell is considered the key mechanism in BPD-related pulmonary epithelial injury [29,30]. LTBR expression was also increased by hyperoxia-stimulated A549 and ATII cells in this study.…”

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases: Recent advancements and prospects

“…A recent study demonstrated that UC-MSCs ameliorate lung injury in ARDS and regulate Yes-associated protein to facilitate AEC II differentiation[ 45 ]. Furthermore, microvesicles derived from UC-MSCs were able to enhance alveolar development by promoting AEC II proliferation and ameliorating lung inflammation in an antenatal rat model of BPD[ 46 ]. In addition, UC-MSCs have antifibrotic properties and can secrete a variety of cytokines that effectively reverse pulmonary fibrosis[ 47 ].…”

Secretome as a Tool to Treat Neurological Conditions: Are We Ready?

“…This fraction is composed of membrane-coated vesicles enclosed by a lipid bilayer, rich in integrins, transpanins, and other ligands that support transport, adhesion, and endocrine effects, and contain bioactive components like lipids, proteins, or nucleic acids [43]. Moreover, EVs are classified according to their origin and size [9], i.e., with diameters ranging between 30 nm and 200 nm in exosomes [44] and 100 nm and 900 nm in microvesicles (MVs) [45].…”

“…Microvesicles, also known as ectosomes [9], are more heterogeneous than exosomes [32] and represent medium-sized EVs. These vesicles have a range of sizes that vary from 100 to 900 nm [45], with the most frequently mentioned size being between 200 and 400 nm [61][62][63]. These EVs originate from the plasma membrane of the cell, and their common surface markers are specific integrins (e.g., macrophage-1 antigen), selectins (p-selectin) [9,32], CD63 [64], CD9, CD81, TSG101, Alix [45], and Annexin V [65].…”

“…These vesicles have a range of sizes that vary from 100 to 900 nm [45], with the most frequently mentioned size being between 200 and 400 nm [61][62][63]. These EVs originate from the plasma membrane of the cell, and their common surface markers are specific integrins (e.g., macrophage-1 antigen), selectins (p-selectin) [9,32], CD63 [64], CD9, CD81, TSG101, Alix [45], and Annexin V [65]. These vesicles also express some regulatory molecules, such as the programmed death-ligand 1, Gal-1, and TGF-β [66].…”