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Therapeutic potential of mesenchymal stem cell transplantation in a nitrofen-induced congenital diaphragmatic hernia rat model

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Abstract

Purpose

The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model.

Methods

Pregnant rats were exposed to nitrofen on embryonic day 9.5 (E9.5). MSCs were isolated from the enhanced green fluorescent protein (eGFP) transgenic rat lungs. The MSCs were transplanted into the nitrofen-induced E12.5 rats via the uterine vein, and the E21 lung explants were harvested. The study animals were divided into three: the control group, the nitrofen-induced left CDH (CDH group), and the MSC-treated nitrofen-induced left CDH (MSC-treated CDH group). The specimens were morphologically analyzed using HE and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), surfactant protein-C (SP-C), and α-smooth muscle actin.

Results

The alveolar and medial walls of the pulmonary arteries were significantly thinner in the MSC-treated CDH group than in the CDH group. The alveolar air space areas were larger, while PCNA and the SP-C positive cells were significantly higher in the MSC-treated CDH group, than in the CDH group. MSC engraftment was identified on immunohistochemical staining of the GFP in the MSC-treated CDH group.

Conclusions

MSC transplantation potentially promotes alveolar and pulmonary artery development, thereby reducing the severity of pulmonary hypoplasia.

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Acknowledgments

The authors wish to thank Mr. Brian Quinn for supporting the manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science.

Conflict of interest

The authors do not have any conflicts of interest related to this paper.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Ratih Yuniartha, Fatima Safira Alatas, Kouji Nagata, Masaaki Kuda, Yusuke Yanagi, Genshiro Esumi, Yoshiaki Kinoshita & Tomoaki Taguchi

  2. Department of Child Health, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia

    Fatima Safira Alatas

  3. Department of Molecular Cell and Oral Anatomy, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

    Takayoshi Yamaza

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  1. Ratih Yuniartha
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  2. Fatima Safira Alatas
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  4. Masaaki Kuda
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  9. Tomoaki Taguchi
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Correspondence to Kouji Nagata.

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Yuniartha, R., Alatas, F.S., Nagata, K. et al. Therapeutic potential of mesenchymal stem cell transplantation in a nitrofen-induced congenital diaphragmatic hernia rat model. Pediatr Surg Int 30, 907–914 (2014). https://doi.org/10.1007/s00383-014-3576-9

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  • DOI: https://doi.org/10.1007/s00383-014-3576-9

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