Mesenchymal stem cell therapy in acute lung injury: is it time for a clinical trial?
- 1Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, Northern Ireland
- 2Centre for Infection and Immunity, Queen's University Belfast, Belfast, Northern Ireland
- Correspondence to Dr Daniel F McAuley, Centre for Infection and Immunity, Queen's University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland;
Contributors RMS wrote the initial draft and DFM edited and finalised the final version.
Despite decades of research, no specific pharmacological therapy to treat acute lung injury (ALI) has been identified. At present, the only effective therapies act by limiting iatrogenic injury associated with positive fluid balance1 or mechanical ventilation.2 3 As efforts to pharmacologically modulate the complex inflammatory process which leads to alveolar injury have been unsuccessful,4 focus has changed to cell based therapy, aimed at utilising stems cells which have pleiotropic effects and which respond appropriately to local signalling molecules.
Stem cells have the capacity for limitless self-renewal and differentiation. Mesenchymal stem cells (MSC) are multipotent adult stem cells with the capacity to differentiate into many different cell types, including alveolar cells. There are several mechanisms through which MSCs could potentially be used for attenuating lung injury and augmenting repair.5 On the basis of the currently available data, and supported by two papers,6 7 the most important therapeutic effect of exogenously administered MSCs is probably through the paracrine secretion of mediators such as growth factors and cytokines to modulate localised inflammation and tissue repair.8 Gupta et al found treatment with MSCs improved bacterial clearance in a mouse model of gram-negative pneumonia, which was due in part to lipocalin 2 production by MSCs,6 while Curley et al showed that MSC therapy improved lung repair via a paracrine mechanism that was keratinocyte growth factor (KGF)-dependent.7 However, cell contact-dependent mechanisms, via the gap junction channel protein connexin-43, have also been described.9 The other main effect of exogenously administered MSCs is their localisation to the site of …