Can mesenchymal stem cell and retinoic acid therapies more effectively reduce lung damage due to bronchopulmonary dysplasia?
7 affiliations
- 1Neonatologist, HSU Izmir Faculty of Medicine, Dr Behcet Uz Child Disease and Surgery Training and Research Hospital
- 2School of Medicine, Department of Histology, Van Yüzüncü Yıl University
- 3Department of Laboratory Animal Science, Dokuz Eylul University
- 4Division of Stem Cell, HSU Gülhane Faculty of Medicine, Department of Histology
- 5School of Medicine, Department of Histology, Izmir Tınaztepe University
- 6Division of Neonatology, School of Medicine, Department of Pediatrics, Izmir Tınaztepe University
- 7School of Medicine, Department of Histology, Ege University
Abstract
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.
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BibTeX
@article{ozdemir2026mesenchymal,
title = {{Can mesenchymal stem cell and retinoic acid therapies more effectively reduce lung damage due to bronchopulmonary dysplasia?}},
author = {Senem Alkan Özdemir and Eda Açıkgöz and Aslı Çelik and Osman Yılmaz and Meral Sarper and Gurur Garip and Esra Özer and Gülperi Öktem},
journal = {Italian Journal of Pediatrics},
year = {2026},
month = oct,
doi = {10.1186/s13052-026-02299-2},
url = {https://doi.org/10.1186/s13052-026-02299-2},
note = {CC BY},
}
RIS
TY - JOUR
TI - Can mesenchymal stem cell and retinoic acid therapies more effectively reduce lung damage due to bronchopulmonary dysplasia?
AU - Senem Alkan Özdemir
AU - Eda Açıkgöz
AU - Aslı Çelik
AU - Osman Yılmaz
AU - Meral Sarper
AU - Gurur Garip
AU - Esra Özer
AU - Gülperi Öktem
PY - 2026
DA - 2026/10/25
JO - Italian Journal of Pediatrics
DO - 10.1186/s13052-026-02299-2
UR - https://doi.org/10.1186/s13052-026-02299-2
AB - 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.
SN - 1824-7288
SN - 1720-8424
ER -