Transamniotic Stem Cell Therapy for Experimental Congenital Diaphragmatic Hernia: Structural, Transcriptional, and Cell Kinetics Analyses in the Nitrofen Model
| Autor: | Daniel F. Labuz, Sarah A. Tracy, Stefanie P. Lazow, Dario O. Fauza, Alexander V. Chalphin, Ina Kycia, David Zurakowski |
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| Rok vydání: | 2020 |
| Předmět: |
Embryology
medicine.medical_treatment Mesenchymal Stem Cell Transplantation Umbilical cord Andrology chemistry.chemical_compound Pregnancy medicine Animals Radiology Nuclear Medicine and imaging Lung Fetus business.industry Phenyl Ethers Mesenchymal stem cell Obstetrics and Gynecology Congenital diaphragmatic hernia Amniotic stem cells Mesenchymal Stem Cells General Medicine Stem-cell therapy Nitrofen medicine.disease Disease Models Animal Kinetics medicine.anatomical_structure chemistry Pediatrics Perinatology and Child Health Female Bone marrow business Hernias Diaphragmatic Congenital |
| Zdroj: | Fetal diagnosis and therapy. 48(5) |
| ISSN: | 1421-9964 |
| Popis: | Purpose: We examined select pulmonary effects and donor cell kinetics after transamniotic stem cell therapy (TRASCET) in a model of congenital diaphragmatic hernia (CDH). Methods: Pregnant dams (n = 58) received nitrofen on gestational day 9.5 (E9) to induce fetal CDH. Fetuses (n = 681) were divided into 4 groups: untreated (n = 99) and 3 groups receiving volume-matched intra-amniotic injections on E17 of either saline (n = 142), luciferase-labeled amniotic fluid-derived mesenchymal stem cells (afMSCs; n = 299), or acellular recombinant luciferase (n = 141). Pulmonary morphometry, quantitative gene expression of pulmonary vascular tone mediators, or screening for labeled afMSCs were performed at term (E22). Statistical comparisons were by Mann-Whitney U-test, nested ANOVA, and Wald test. Results: TRASCET led to significant downregulation of endothelial nitric oxide synthase and endothelin receptor-A expressions compared to both untreated and saline groups (both p < 0.001). TRASCET also led to a significant decrease in arteriole wall thickness compared to the untreated group (p < 0.001) but not the saline group (p = 0.180). Donor afMSCs were identified in the bone marrow and umbilical cord (p = 0.035 and 0.015, respectively, vs. plain luciferase controls). Conclusions: The effects of TRASCET in experimental CDH appear to be centered on the pulmonary vasculature and to derive from circulating donor cells. |
| Databáze: | OpenAIRE |
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