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

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

doi:10.1007/s00383-014-3576-9

Cited by 30 publications

(12 citation statements)

References 30 publications

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“…Other work using amniotic fluid stem cells (SC), administered intra‐amniotically to the NF‐rat in early gestation and resulted in a restored terminal bud count in hypoplasic lung explants . More recently human lung SC have been shown to promote lung maturation . Multiple other therapies including (Table ) ghrelin, estrogen, bombesin, cystic fibrosis transmembrane regulator gene therapy (CFTR), and epidermal growth factor (EGF) in the NF‐rat have again improved yet failed to normalize LBWR …”

Section: Resultsmentioning

confidence: 99%

“…52 More recently human lung SC have been shown to promote lung maturation. 69 Multiple other therapies including (Table 3) ghrelin, estrogen, bombesin, cystic fibrosis transmembrane regulator gene therapy (CFTR), and epidermal growth factor (EGF) in the NF-rat have again improved yet failed to normalize LBWR. 43,53,54,[56][57][58] Two studies in rabbits (Table 3) employed an IT fibrin gel plug on GD27, both improving LBWR but not to the levels of normal suture ligation.…”

Section: Isolated Studiesmentioning

confidence: 99%

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Medical interventions to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia: A systematic review

Eastwood

Russo

Toelen

et al. 2015

Pediatric Pulmonology

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We aimed to systematically review all published pre-clinical research on prenatal medical treatment of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Background The neonatal mortality due to isolated CDH remains high. Whether fetal endoscopic tracheal occlusion (FETO) reduces mortality is still to be demonstrated. Therefore more potent preferentially medical therapy would be welcomed. Methods We searched MEDLINE (Pubmed), Embase and the Web of Science including all studies from the earliest date (1951) to December 2013. Article quality was assessed using the modified CAMRADES checklist. Inclusion criteria were those animal studies addressing prenatal medical interventions and principal variables were confirmation of a diaphragmatic defect, lung to body weight ratio (LBWR), formal airway morphometry or DNA/protein content. Results In total 983 articles were identified. Following abstract review, 96 articles were assessed by two authors in agreement with a third for eligibility. Of these, 43 were included in the final analysis. The median number of study quality checklist items (maximum 10) scored was 4 (IQ range: 2-5). Thirty (69.8%) of studies were in the nitrofen rat. The majority were treated with vitamins or glucocorticoids. Single studies reported some improvement in lung morphology with alternative therapies. It was impossible to identify a pattern in animal model selection or creation, mode, time point or duration of treatment and readouts. Only one study reported a sample size calculation. Conclusion Comparison in pre-clinical studies in CDH is challenging due to methodological variation. Agreed standardized methods need to be applied in future investigation of new medical therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Isolated Studiesmentioning

confidence: 99%

Medical interventions to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia: A systematic review

Eastwood

Russo

Toelen

et al. 2015

Pediatric Pulmonology

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“…MSC administration reduces the nitrofen-induced 14 Stem Cell Therapy for Neonatal Lung Diseases 342 alveolar walls thickness and saccules underdevelopment, increases the endogenous pool of surfactant, and normalizes medial wall thickness of the pulmonary artery (Yuniartha et al 2014 ) (Fig. 14.8 ).…”

Section: Mscs For Cdhmentioning

confidence: 99%

“…Prenatal lung-derived MSC transplantation, injected via the uterine vein in the bilateral horn of the uterus of the dams, signifi cantly improves alveolar wall thickness and alveolar air space area. ( b ) Immunohistochemical staining for alpha smooth muscle actin: the wall medial thickness of the pulmonary arteries in CDH lungs, signifi cantly higher than controls, is restored by prenatal MSC administration ( Adapted from Yuniartha et al 2014 ;with permission) This rescue therapy appeared to be safe and effective up to 10 months of life: hyperoxic-exposed neonatal mice treated in the neonatal period had preserved alveolar architecture, signifi cantly improved exercise capacity and reduced pulmonary hypertension in these long-term experiments (Alphonse et al 2014 ). In immunocompetent rats, ECFCs from term cord were able to reduce bleomycin-induced pulmonary hypertensionas determined by right ventricular hypertrophy, although the treatment did not improve lung histology (Baker et al 2013a ) ECFCs from preterm cord did not elicit any response.…”

Section: Ecfcs For Bpdmentioning

confidence: 99%

Regenerative Medicine - from Protocol to Patient

2016

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“…32 Yuniartha et al also tested the therapeutic effects of adult-lung-derived mesenchymal stromal cell administration in the nitrofen model and showed stem cell engraftment in the lung following maternal intrauterine vein injection. 33…”

Section: Nitrofen Modelmentioning

confidence: 99%

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

et al. 2019

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Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.

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

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

Cited by 30 publications

References 30 publications

Medical interventions to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia: A systematic review

Medical interventions to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia: A systematic review

Regenerative Medicine - from Protocol to Patient

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

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