Efficacy of mesenchymal stem cells depends on administration route in a murine model of acid inhalation ARD8

INTRODUCTION. Acute respiratory distress syndrome (ARDS) is still associated with high mortality, as only few effective therapies are available. Mesenchymal stem cells (MSCs) showed beneficial effects in various experimental ARDS model, by fine balancing inflammation with increased ability of eliminating the noxa without additional injury. Data on the effects of MSCs in acid inhalation-induced ARDS still lack. OBJECTIVES. Aim of this study was to test the therapeutic effects of MSCs, administered by intravenous (iv) and intraperitoneal (ip) route, in a murine model of ARDS induced by acid inhalation. METHODS. Intubated and ventilated mice received 1.5 mL/kg HCl (0.1M) into the right bronchus and were immediately extubated. One hour after acid instillation, MSCs were injected ip or iv (106 cells in 200 µl solution for both routes). Mice treated by iv or ip PBS (200µl) served as controls. Twenty-four hours after MSCs administration mice were sacrificed and arterial blood gases (FiO2 = 0.21) and bronchoalveolar lavage (BAL) were analyzed to assess lung injury. RESULTS. Survival at 24 hours was 95% for MSCs ip and 85% for iv; no mice died in the PBS groups. Mice treated with MSCs ip showed significantly (p=0.013) higher partial pressure of oxygen in arterial blood (Figure 1) associated with reduction in number of neutrophils recovered in BAL (p=0.055), compared to PBS ip group (Figure 2). In contrast, mice that received MSCs intravenously did not show any beneficial effects in terms of oxygenation and neutrophils recruitment in the alveolar space, if compared to PBS iv group. CONCLUSIONS. MSCs injected intraperitoneally 1 h after onset of acid-induced experimental ARDS determine a significant improvement in oxygenation at 24 h, possibly by dampening recruitment of activated neutrophils in the alveolar space. On the other hand, MSCs iv do not seem to attenuate acid-induced ARDS, maybe because acid environment in lung parenchyma destroy a significant amount of MSCs as they pass through lung vascular tree.