Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma

Background Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. Methods This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were randomly divided into two groups (n = 10), and treated either with a single intrabronchial application of autologous AD-MSC or oral dexamethasone for three weeks. A targeted clinical examination with determination of clinical score, maximal change in pleural pressure during the breathing cycle, and an endoscopic examination of the airways were performed at baseline and three weeks after treatment. Bronchoalveolar lavage fluid was analyzed cytologically, and IL-1 beta, IL-4, IL-8, IL-17, TNF alpha and IFN gamma mRNA and protein concentrations were measured at baseline and three weeks. The horses were then monitored over one year for recurrence of SEA. A non-inferiority analysis and a linear mixed-effects model were performed to assess differences between treatments. Results The non-inferiority of AD-MSC treatment was not established. However, AD-MSC administration significantly ameliorated the clinical score (P = 0.01), decreased the expression of IL-17 mRNA (P = 0.05) and IL-1 beta (P <= 0.001), IL-4 (P <= 0.001), TNF alpha (P = 0.02) protein levels, and had a positive long-term effect on SEA-associated clinical signs (P = 0.02). Conclusions Intrabronchial administration of AD-MSC had limited short-term anti-inflammatory effects but improved the clinical signs of SEA at one year.

Automated summary

This study assessed the safety and effectiveness of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) in horses with severe equine asthma (SEA). The results showed that AD-MSC treatment significantly improved clinical scores and reduced the expression of inflammatory markers. Furthermore, the treatment had a positive long-term effect on SEA-related clinical signs.