Abstract
BackgroundPrimary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion.MethodsFour donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 107 MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue.ResultsAll LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs.ConclusionsThese initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury.Electronic supplementary materialThe online version of this article (doi:10.1186/2047-1440-3-19) contains supplementary material, which is available to authorized users.
Highlights
Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation
Adherent stromal cells isolated from bone marrow, adipose, and other sources, including mesenchymal stromal cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent immunomodulatory properties and have been increasingly investigated in a range of inflammatory and autoimmune conditions [15,16,17]
In an initial small-scale pilot and feasibility study, we found that airway administration of bone marrow-derived MAPCs decreased a number of inflammatory markers provoked by prolonged cold storage and subsequent reperfusion in four suboptimal donor lungs
Summary
Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Adherent stromal (stem) cells isolated from bone marrow, adipose, and other sources, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent immunomodulatory properties and have been increasingly investigated in a range of inflammatory and autoimmune conditions [15,16,17]. Both systemic and intratracheal MSC administration reduces inflammation and injury in a wide spectrum of preclinical lung injury models [18,19]. These properties make MSCs and MAPCs interesting for use as a cellular therapy in solid-organ transplantation [21,22]
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