Italian journal of pediatrics · 2026
Can mesenchymal stem cell and retinoic acid therapies more effectively reduce lung damage due to bronchopulmonary dysplasia?
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Özdemir Senem Alkan, Açıkgöz Eda, Çelik Aslı, Yılmaz Osman, Sarper Meral, Garip Gurur, Özer Esra, Öktem Gülperi
Аннотация
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 (1 × 106) 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: Hyperoxia significantly impaired lung structure, as demonstrated by increased mean linear intercept (MLI), alveolar size, and vessel wall thickness, along with decreased alveolar tissue distribution compared to the control group (p < 0.0001). Treatment with mesenchymal stem cells (MSCs) significantly improved these parameters compared to the hyperoxic group (p < 0.0001). Notably, combined MSCs+retinoic acid (RA) therapy resulted in further improvement, with morphometric findings approaching those of the control group. In addition, α-smooth muscle actin (α-SMA) expression, which was significantly increased in the hyperoxic group (p < 0.0001), was reduced in both treatment groups, with the most pronounced decrease observed in the MSCs + RA group.
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.
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 (1 × 106) 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: Hyperoxia significantly impaired lung structure, as demonstrated by increased mean linear intercept (MLI), alveolar size, and vessel wall thickness, along with decreased alveolar tissue distribution compared to the control group (p < 0.0001). Treatment with mesenchymal stem cells (MSCs) significantly improved these parameters compared to the hyperoxic group (p < 0.0001). Notably, combined MSCs+retinoic acid (RA) therapy resulted in further improvement, with morphometric findings approaching those of the control group. In addition, α-smooth muscle actin (α-SMA) expression, which was significantly increased in the hyperoxic group (p < 0.0001), was reduced in both treatment groups, with the most pronounced decrease observed in the MSCs + RA group.
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.