Safety and efficacy profile of cryopreserved mesenchymal stem cells for the treatment of acute respiratory distress syndrome.

Background & Aim Introduction The treatment of critical conditions such as acute respiratory distress syndrome (ARDS) requires immediate intervention. The validation of the cryostorage protocol for Mesenchymal stem cells (MSCs) is necessary to streamline their use as an "off the shelf" therapy in acute clinical conditions. The aim of this work was to demonstrate that allogeneic cryopreserved menstrual stem cells (MenSCs) possess an adequate safety and efficacy profile in an ARDS preclinical model. Methods, Results & Conclusion Methods The therapeutic effect of cryopreserved MenSCs was evaluated in a murine model of ARDS induced with LPS. MenSCs were produced and cryopreserved in GMP conditions following appropriate quality control standards. The release criteria included a viability rate >80% upon thawing, the retention of immunosuppressive capacity and cell response to inflammatory signals. The animals were then treated with different doses of MenSCs ranging from 0.25 × 105 to 1.25 × 106. Lung mechanics, histology, biochemical parameters, cytokines and factors were evaluated in lung tissue, BALF and serum at 2 and 7 days post-injection. Results The treatment with cryopreserved MenSCs improved lung function and reduced alveolar collapse, tissue cellularity, elastic and collagen fiber content in the lung. However, this occurred with an optimal dose of 1 × 105. Interestingly, testing doses higher or lower to the determined optimal dose showed no statistically significant beneficial effect. MenSCs administration also reduced the levels of pro-inflammatory cytokines and increased anti-inflammatory in lung tissue as well as in BALF and serum. Biochemical analysis, altered in ARDS animals, revealed an improvement after MenSCs administration, particularly in hepatic and pancreatic functional markers. Conclusions Cryopreserved MenSCs treatment decreases lung injury and improves lung function in an experimental model of ARDS. Determination of an optimal dose is required for securing a safe and effective treatment. Furthermore, studies with MenSCs in a larger animal model are needed to safeguard their clinical application.