Philip DeKoninck1, Jaan Toelen1, Xenia Roubliova1, Shea Carter2, Michela Pozzobon3, Francesca Maria Russo1, Jute Richter1, Pieter-Jan Vandersloten1, Erik Verbeken4, Paolo De Coppi5, Jan Deprest1. 1. Organ systems cluster, Department of Development and Regeneration, and Center for Surgical Technologies, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. 2. Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. 3. Stem Cells and Regenerative Medicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Department of Woman and Child Health, University of Padova, Padova, Italy. 4. Department of Pathology, Group Biomedical Sciences, University Hospitals Leuven, Belgium. 5. Department of Pediatric Surgery, UCL Institute of Child Health and Great Ormond St Hospital, London, United Kingdom.
Abstract
OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH. METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 μL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B). RESULTS: CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection. CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity.
OBJECTIVE: This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH. METHODS: In time-mated pregnant does a left diaphragmatic defect was created at d23 (term = 31). At d28, previously operated fetuses were assigned to either TO and injection with 70 μL of phosphate buffered saline (PBS) or 1.0 × 10(6) c-Kit positive hAFSC expressing LacZ or were left untouched (CDH). Harvesting was done at d31 to obtain their lung-to-body weight ratio (LBWR), airway and vascular lung morphometry, X-gal staining and immunohistochemistry for Ki67 and surfactant protein-B (SP-B). RESULTS:CDH-induced pulmonary hypoplasia is countered by TO + PBS, this reverses LBWR, mean terminal bronchiole density (MTBD) and medial thickness to normal. The additional injection of hAFSC decreases MTBD and results in a non-significant decrease in muscularization of intra-acinary vessels. There were no inflammatory changes and LacZ positive hAFSC were dispersed throughout the lung parenchyma 4 days after injection. CONCLUSION: HAFSC exert an additional effect on TO leading to a decrease in MTBD, a measure of alveolar number surrounding the terminal bronchioles, without signs of toxicity.
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