Shohei Takayama1,2, Kohei Sakai3, Shigehisa Fumino3, Taizo Furukawa3, Tsunao Kishida4, Osam Mazda4, Tatsuro Tajiri3. 1. Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. taka0815@koto.kpu-m.ac.jp. 2. Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan. taka0815@koto.kpu-m.ac.jp. 3. Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. 4. Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Abstract
PURPOSE: We aimed to evaluate the effect of human mesenchymal stem cells (hMSCs) on congenital diaphragmatic hernia (CDH) by intra-amniotic injection in a rat CDH model. METHODS: Nitrofen (100 mg) was administered to pregnant rats at E9.5. hMSCs (1.0 × 106) or PBS was injected into each amniotic cavity at E18, and fetuses were harvested at E21. The fetal lungs were classified into normal, CDH, and CDH-hMSCs groups. To determine the lung maturity, we assessed the alveolar histological structure by H&E and Weigert staining and the alveolar arteries by Elastica Van Gieson (EVG) staining. TTF-1, a marker of type II alveolar epithelial cells, was also evaluated by immunohistochemical staining and real-time reverse transcription polymerase chain reaction. RESULTS: The survival rate after intra-amniotic injection was 72.1%. The CDH-hMSCs group had significantly more alveoli and secondary septa than the CDH group (p < 0.05). The CDH-hMSCs group had larger air spaces and thinner alveolar walls than the CDH group (p < 0.05). The medial and adventitial thickness of the pulmonary artery in the CDH-hMSCs group were significantly better (p < 0.001), and there were significantly fewer TTF-1-positive cells than in the CDH group (p < 0.001). CONCLUSION: These results suggest that intra-amniotic injection of hMSCs has therapeutic potential for CDH.
PURPOSE: We aimed to evaluate the effect of human mesenchymal stem cells (hMSCs) on congenital diaphragmatic hernia (CDH) by intra-amniotic injection in a ratCDH model. METHODS:Nitrofen (100 mg) was administered to pregnant rats at E9.5. hMSCs (1.0 × 106) or PBS was injected into each amniotic cavity at E18, and fetuses were harvested at E21. The fetal lungs were classified into normal, CDH, and CDH-hMSCs groups. To determine the lung maturity, we assessed the alveolar histological structure by H&E and Weigert staining and the alveolar arteries by Elastica Van Gieson (EVG) staining. TTF-1, a marker of type II alveolar epithelial cells, was also evaluated by immunohistochemical staining and real-time reverse transcription polymerase chain reaction. RESULTS: The survival rate after intra-amniotic injection was 72.1%. The CDH-hMSCs group had significantly more alveoli and secondary septa than the CDH group (p < 0.05). The CDH-hMSCs group had larger air spaces and thinner alveolar walls than the CDH group (p < 0.05). The medial and adventitial thickness of the pulmonary artery in the CDH-hMSCs group were significantly better (p < 0.001), and there were significantly fewer TTF-1-positive cells than in the CDH group (p < 0.001). CONCLUSION: These results suggest that intra-amniotic injection of hMSCs has therapeutic potential for CDH.
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