Human Umbilical Cord Mesenchymal Stem Cells Improve Lung Function in Chronic Obstructive Pulmonary Disease Rat Model Through Regulating Lung Microbiota

Abstract

Background: The use of human umbilical cord mesenchymal stem cells (UC-MSCs) has shown promise in improving the pathophysiological characteristics of rats with chronic obstructive pulmonary disease (COPD). However, more research is needed to understand the exact mechanism behind their therapeutic effects and their impact on lung microbiota.

Methods: To investigate this, rats were randomly assigned to one of 3 groups: Control, COPD + vehicle, and COPD + UC-MSCs group. Lung function changes after UC-MSCs therapy were evaluated weekly for 6 weeks. Additionally, lactate dehydrogenase (LDH), TNF (tumor necrosis factor)-α, IL (interleukin)-6, and IL-1β level in bronchoalveolar lavage fluid (BALF) were analyzed. Arterial blood gas and weight were recorded. Hematoxylin and eosin (HE) staining was used to examine lung pathology, while changes in the lung microbiota were evaluated through 16S rRNA sequencing.

Results: The administration of UC-MSCs in rats led to a progressive amelioration of COPD, as demonstrated by enhanced lung function and reduced inflammatory response. UC-MSCs treatment significantly altered the structure and diversity of the lung microbiota, effectively preventing microbiota dysbiosis. This was achieved by increasing the abundance of Bacteroidetes and reducing the levels of Proteobacteria. Additionally, treatment with UC-MSCs reduced the activation of pathways associated with COPD, including microbial metabolism, ABC transporters, and Quorum sensing. The group of UC-MSCs showed increased metabolic pathways, such as amino acid biosynthesis, purine metabolism, starch and sucrose metabolism, and biosynthesis of secondary metabolites, compared to the COPD group.

Conclusions: The use of UC-MSCs was found to reduce inflammation and improve lung function in rats with COPD. The mechanism may be related to the lung microbiota, as UC-MSCs improved the communities of lung microbiota and regulated dysregulated metabolic pathways.

Keywords: COPD; UC-MSCs; lung function; microbiota; therapeutic effect.