Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints

Abstract

Mesenchymal stromal cells (MSCs) have been proposed as a potential therapy to treat congenital and acquired lung diseases. Due to their tissue-regenerative, anti-fibrotic, and immunomodulatory properties, MSCs combined with other therapy or alone could be considered as a new approach for repair and regeneration of the lung during disease progression and/or after post- surgical injury. Children interstitial lung disease (chILD) represent highly heterogeneous rare respiratory diseases, with a wild range of age of onset and disease expression. The chILD is characterized by inflammatory and fibrotic changes of the pulmonary parenchyma, leading to gas exchange impairment and chronic respiratory failure associated with high morbidity and mortality. The therapeutic strategy is mainly based on the use of corticosteroids, hydroxychloroquine, azithromycin, and supportive care; however, the efficacy is variable, and their long-term use is associated with severe toxicity. The role of MSCs as treatment has been proposed in clinical and pre-clinical studies. In this narrative review, we report on the currently available on MSCs treatment as therapeutical strategy in chILD. The progress into the therapy of respiratory disease in children is mandatory to ameliorate the prognosis and to prevent the progression in adult age. Cell therapy may be a future therapy from both a pediatric and pediatric surgeon’s point of view.

Role of Mesenchymal Stem/Stromal Cells in Modulating Ischemia/Reperfusion Injury: Current State of the Art and Future Perspectives

“…They have been shown capable of decreasing inflammation and IRI in both in vitro and in vivo models, and those effects were mediated, at least in part, by the paracrine activity of MSCs ( Figure 1 ) [ 99 ]. MSC therapeutic action has also been evaluated both in human lung diseases [ 19 , 100 , 101 , 102 , 103 ] and in different lung experimental models [ 19 , 55 , 97 , 104 , 105 ]. In those cases, MSCs and/or their products were capable of potentiating anti-microbial action, and mitigating both lung injury and inflammation, as found with IRI of LTx.…”

Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration

“…Overall, plenty of preclinical studies have provided convincing evidence of the effectiveness of MSC based therapy in the treatment of many lung disorders. As recently reported, MSCs treatment improved disease-associated parameters in acute respiratory distress syndrome (ARDS) as well as in chronic lung disease of the preterm infants (e.g., bronchopulmonary dysplasia), other chronic obstructive pulmonary diseases, pulmonary hypertension and idiopathic pulmonary fibrosis [ 6 , 7 , 8 ]. Moreover, it has been reported the ability of MSCs to differentiate in vitro into ATII epithelial cells.…”

Allogeneic Mesenchymal Stromal Cells as a Global Pediatric Prospective Approach in the Treatment of Respiratory Failure Associated with Surfactant Protein C Dysfunction

“…Cell-based therapy represents a new approach in regenerative medicine [1,2]. In particular, mesenchymal stromal cells (MSCs) have gained great interest in congenital and acquired respiratory disease treatment [3]. MSCs show an innate self-renewal capacity, they maintain differentiation potential, into multiple tissue-forming cell lineages, even after in vitro expansion [4].…”

“…The clinical presentation and prognosis of ILD in children (chILD) are variable, ranging from mild nonspecific symptoms with complete recovery to a severe clinical picture, leading to chronic respiratory failure [3].…”