Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

Abstract

Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells residing in many tissues, including the lung. MSCs have long been regarded as a promising tool for cell-based therapy because of their ability to replace damaged tissue by differentiating into the resident cell and repopulating the injured area. Their ability to release soluble factors and extracellular vesicles has emerged as crucial in the resolution of inflammation and injury. There is a growing literature on the use of MSCs and MSC secretome to hamper inflammation in different lung pathologies, including: asthma, pneumonia, acute lung injury (ALI), pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). However, their potential therapeutic role in the context of Cystic Fibrosis (CF) lung inflammation is still not fully characterized. CF morbidity and mortality are mainly due to progressive lung dysfunction. Lung inflammation is a chronic and unresolved condition that triggers progressive tissue damage. Thus, it becomes even more important to develop innovative immunomodulatory therapies aside from classic anti-inflammatory agents. Here, we address the main features of CF and the implications in lung inflammation. We then review how MSCs and MSC secretome participate in attenuating inflammation in pulmonary pathologies, emphasizing the significant potential of MSCs as new therapeutic approach in CF.

Cell-Based Therapeutic Approaches for Cystic Fibrosis

“…They also contribute to tissue regeneration, angiogenesis, and clearance of microorganisms. Indeed, the secretory and paracrine effects of MSC have continued to be extensively studied, and it is widely accepted in the MSC field that their secretome is predominantly responsible for the intercellular crosstalk between MSC and targeted cells [111][112][113].…”

Heat Shock Preconditioning Mesenchymal Stem Cells Attenuate Acute Lung Injury via Reducing NLRP3 Inflammasome Activation in Macrophages

“…Our previous researches provided reliable results on the bene cial effects of MSCs on improving liver ischemia/reperfusion injury (IRI) in vivo and in vitro [10,11]. In addition, our and other several studies have also shown that MSCs could alleviate lipopolysaccharide (LPS)-induced ALI via their well-de ned roles in immunomodulation and differentiation into multiple different cell types, including adipocytes, osteoblasts and lung-related cell types [12][13][14][15][16][17].…”

Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies

“…Mesenchymal stem cells (MSCs) are an allogenic source of cells that have been investigated for their application in CF cell-based therapy due to their immunomodulatory and anti-inflammatory properties (reviewed in ( Caretti et al, 2019 )). In favor of their potential for CF cell therapy, MSCs co-cultured with CF immortalized airway epithelial cells at air-liquid interface have demonstrated acquisition of an epithelial phenotype, and subsequent restoration of functional CFTR protein ( Carbone et al, 2014 ; Carbone et al, 2018 ).…”