Bone marrow mesenchymal stem cell-conditioned medium facilitates fluid resolution via miR-214-activating epithelial sodium channels.

Yan Ding,Hongguang Nie,Yapeng Hou,Yong Cui

doi:10.1002/mco2.40

Yan Ding, Hongguang Nie + Show 2 more

Open Access

https://doi.org/10.1002/mco2.40

Copy DOI

Abstract

Acute lung injury (ALI) is featured with severe lung edema at the early exudative phase, resulting from the imbalance of alveolar fluid turnover and clearance. Mesenchymal stem cells (MSCs) belong to multipotent stem cells, which have shown potential therapeutic effects during ALI. Of note, MSC‐conditioned medium (MSC‐CM) improved alveolar fluid clearance (AFC) in vivo, whereas the involvement of miRNAs is seldom known. We thus aim to explore the roles of miR‐214 in facilitating MSC‐CM mediated fluid resolution of impaired AFC. In this study, AFC was increased significantly by intratracheally administrated MSC‐CM in lipopolysaccharide‐treated mice. MSC‐CM augmented amiloride‐sensitive currents in intact H441 monolayers, and increased α‐epithelial sodium channel (α‐ENaC) expression level in H441 and mouse alveolar type 2 epithelial cells. Meanwhile, MSC‐CM increased the expression of miR‐214, which may participate in regulating ENaC expression and function. Our results suggested that MSC‐CM enhanced AFC in ALI mice in vivo through a novel mechanism, involving miR‐214 regulation of ENaC.

Highlights

In our recently published paper, we investigated miR-124-5p, which existed in Mesenchymal stem cells (MSCs)-conditioned medium (MSC-CM), and found that the miR-124-5p participated in the regulation of MSC-CM in lipopolysaccharide (LPS)-induced Acute lung injury (ALI) by targeting α-epithelial sodium channel (ENaC).[23]
To investigate the influence of MSC-CM on the reabsorption of fluid in mouse distal lung, we proposed alveolar fluid clearance (AFC) in vivo in C57 mice by measuring the instillate of 5% bovine serum albumin (BSA)
In order to clarify the augment of AFC by MSC-CM is correlated with the activation of ENaC, we applied a specific inhibitor of ENaC, amiloride, which downregulated AFC significantly

Summary

Introduction

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are both common and multifactorial clinical syndromes, which are characterized by acute. Mesenchymal stem cells (MSCs) are nonhematopoietic stem-like cells first discovered from the niche of bone marrow, capable of multilineage differentiation, immune regulation, and tissues repair.[12,13,14] Recent studies showed that MSCs have the potential to alleviate the degree of lung injury in diverse disease models through paracrine effects, especially via the carrier of MSC secretome, MSC-conditioned medium (MSC-CM).[15,16,17] Previous studies often focused on cell-based therapy. We have to overcome some obvious hurdles if MSCs are administrated directly in clinical tests, including the provision for numerous MSCs, the deficiency of MSCs quality, and the continuous differentiation of MSCs after in vitro passaging.[18]

Methods

Results

Conclusion