Can mesenchymal stem cell and retinoic acid therapies more effectively reduce lung damage due to bronchopulmonary dysplasia?

Aim: The purpose of the present study was to assess the efficacy of retinoic acid (RA) treatment combined with mesenchymal stem cells (MSCs) compared to MSCs alone in lung injury due to bronchopulmonary dysplasia. Methods: 29 Wistar baby rats on the postnatal third day were used. The experiment started on the postnatal 3rd day after the birth of the cubs. It was continued until the postnatal 14th day. Hyperoxia system was created with the help of Plexiglas chambers. Bone marrow-derived stem cells (1x10 ⁶ ) were administered intraperitoneally. Retinoic acid (500 mcg/kg) was administered intraperitoneally every day starting from the third postnatal day and continued until the 13th postnatal day. Morphometric analyses and histological analyses were performed to provide more detailed assessments of lung structure changes. To assess fibrosis, Masson's trichrome staining was used to show collagen deposition in lung sections. Immunohistochemistry and immunofluorescence staining were performed to assess alpha-smooth muscle actin (α-SMA) expression levels. Results: The enlarged alveolar distribution decreased in the group receiving MSCs, whereas the MSCs+RA group had regular alveolar structures similar to the healthy controls. morphometric analyzes were performed by measuring the mean linear intercept (MLI), alveolar tissue distribution, alveolar size and vessel wall thickness. MLI, alveolar size and vessel wall thickness were significantly higher in the hyperoxic group compared to the control group, whereas alveolar tissue distribution was decreased. In the treatment groups, α-SMA expression was found to be at lower levels compared to hyperoxic group. the results revealed that lung fibrosis-associated α-SMA expression was reduced by MSCs and MSCs+RA treatments. Conclusion: The combined treatment significantly decreased fibrosis and inflammation in the BPD model, and the best reduction was achieved with the combination of the two therapies.