Anna Kelis 1, Chrysovalantis Gkirkis1, Ben Forbes1, James Rickard2, Sally Kim1 & Simon Pitchford1
1Institue of Pharmaceutical Science, King’s College London, SE1 9NH, London, UK.
2Biotherapy Services Ltd, London, SE1 6FE, UK
Summary
Acute lung injury (ALI) and related inflammatory lung diseases remain clinical challenges as there are limited therapeutic options. This urgent unmet need highlights the importance of developing novel regenerative therapies to directly promote lung repair or resolution of injury. Apart from their role in haemostasis, platelets possess anti-inflammatory, pro-resolving, pro-regenerative properties. This study explores the potential for delivering platelet-based therapies in vivo via the inhaled route and investigates the impact of nebulisation on platelet function using in vitro and ex vivo tools.
Utilising a previously characterised in vivo model of ALI, our studies have shown that multiple dose administration of platelets following Lipopolysaccharide (LPS) administration significantly improved lung injury. When platelets were re-administered following platelet depletion and LPS inhalation the levels of haemorrhage in the mouse lung were significantly decreased. In vitro, when exploring platelet function in different preparations before and after nebulisation, it was found that nebulisation significantly reduced platelet aggregation, but chemotactic responses remained intact. Ex vivo, nebulised platelet-based preparations did not impair the viability of precision-cut lung slices (PCLS) following initial evaluation of their safety and efficacy.
Platelet-based therapies show promise in mitigating lung injury and retain key functions post-nebulisation. These findings support further development of inhaled platelet formulations as a novel regenerative strategy for treating lung diseases such as ALI.