A5051658775- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Mesenchymal stem cell research
- Neuroscience of respiration and sleep
- Respiratory Support and Mechanisms
- Pulmonary Hypertension Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Congenital Heart Disease Studies
- Cardiovascular Conditions and Treatments
- Nitric Oxide and Endothelin Effects
- Congenital Anomalies and Fetal Surgery
- Congenital heart defects research
- Ethics and Legal Issues in Pediatric Healthcare
- Neonatal and fetal brain pathology
- Angiogenesis and VEGF in Cancer
- Birth, Development, and Health
- Infant Nutrition and Health
- Renal and related cancers
- Pregnancy and preeclampsia studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Childhood Cancer Survivors' Quality of Life
- Infant Development and Preterm Care
- Extracellular vesicles in disease
- Mechanical Circulatory Support Devices
- Chronic Obstructive Pulmonary Disease (COPD) Research
Ottawa Hospital
2016-2025
University of Ottawa
2016-2025
Ottawa Hospital Research Institute
2016-2025
Children's Hospital of Eastern Ontario
2016-2025
Pediatrics and Genetics
2015-2023
Stem Cell Network
2015-2023
Agricultural Research Institute of Ontario
2021-2023
Ollscoil na Gaillimhe – University of Galway
2023
Regenerative Medicine Institute
2022
Health Canada
2021
Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, older children contributes to significant morbidity mortality. However, current approaches caring for pediatric patients pulmonary have been limited by the lack of consensus guidelines from experts field. In a joint effort American Heart Association Thoracic Society, panel experienced clinicians clinician-scientists was assembled review literature make recommendations on...
Angiogenesis is a critical component of the proliferative endometrial phase menstrual cycle. Thus, we hypothesized that stem cell-like population exist and can be isolated from blood. Mononuclear cells collected blood contained subpopulation adherent which could maintained in tissue culture for >68 doublings retained expression markers CD9, CD29, CD41a, CD44, CD59, CD73, CD90 CD105, without karyotypic abnormalities. Proliferative rate was significantly higher than control umbilical cord...
Background— Bronchopulmonary dysplasia (BPD) and pulmonary emphysema, both significant global health problems, are characterized by a loss of alveoli. Vascular endothelial growth factor ( VEGF) is trophic required for cell survival abundantly expressed in the lung. Methods Results— We report that VEGF blockade decreases lung receptor 2 (VEGFR-2) expression newborn rats impairs alveolar development, leading to simplification capillaries, mimicking BPD. In hyperoxia-induced BPD rats, air space...
Excessive proliferation and impaired apoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs) contribute to vascular obstruction in patients fawn-hooded rats (FHRs) with PA hypertension (PAH). Expression activity mitochondrial superoxide dismutase-2 (SOD2), the major generator H(2)O(2), is known be reduced PAH; however, mechanism therapeutic relevance this are unknown.SOD2 expression PASMCs decreased PAH FHRs PAH. FHR have higher lower rates than Sprague-Dawley rat PASMCs. Moreover,...
<h3>Background</h3> Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model BPD. Human cord is advantageous source that especially appealing for the treatment neonatal diseases. The therapeutic benefit after established long-term safety cord-derived unknown. <h3>Methods</h3> perivascular (PCs) or blood-derived MSCs were...
During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such development. Here, we use MULTI-seq generate scRNA-seq profiles over 66,000 cells from 36 mice normal or impaired secondary hyperoxia with validation some the findings lungs BPD...
Alveolar hypoxia acutely elicits pulmonary vasoconstriction (HPV). Chronic (CH), despite attenuating HPV, causes hypertension (CH-PHT). HPV results, in part, from inhibition of O2-sensitive, voltage-gated potassium channels (Kv) artery smooth muscle cells (PASMCs). CH decreases Kv channel current/expression and depolarizes Ca2+ overload PASMCs. We hypothesize that gene transfer would normalize the circulation (restore reduce CH-PHT), ongoing hypoxia.Adult male Sprague-Dawley rats were...
Hypoxic pulmonary vasoconstriction (HPV) is initiated by inhibition of O 2 -sensitive, voltage-gated (Kv) channels in arterial smooth muscle cells (PASMCs). Kv depolarizes membrane potential (E M ), thereby activating Ca 2+ influx via channels. HPV weak extrapulmonary, conduit arteries (PA) and strong precapillary resistance arteries. We hypothesized that regional heterogeneity reflects a longitudinal gradient the function/expression PASMC -sensitive In adult male Sprague Dawley rats,...
Bronchopulmonary dysplasia (BPD), the chronic lung disease of preterm infants, and pulmonary emphysema, both significant global health problems, are characterized by an arrest in alveolar growth/loss alveoli structures. Mechanisms that inhibit distal growth poorly understood, but recent studies suggest impaired vascular endothelial factor signaling reduced nitric oxide (NO) production decreases vessel developing lung, features observed experimental oxygen-induced BPD. NO exerts its...
Constriction of the ductus arteriosus (DA) is initiated at birth by inhibition O2-sensitive K+ channels in DA smooth muscle cells. Subsequent membrane depolarization and calcium influx through L-type initiates functional closure. We hypothesize that Rho-kinase activation an additional mechanism sustains constriction.The effect increased PO2 on activity expression was assessed DAs from neonates with hypoplastic left-heart syndrome (n=15) rabbits (339 term 99 preterm rabbits). inhibitors...
Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity. Bone marrow derived-mesenchymal stem cells (BM-MSC) prevent lung injury in an O2-induced model BPD. The low level BM-MSC engraftment suggests alternate mechanisms—beyond cell replacement—to account for their therapeutic benefit. We hypothesized that BPD through paracrine-mediated mechanism and preconditioning would further enhance this paracrine effect. To end, conditioned medium (CM) from (MSCcm) or...
Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or destruction. Both conditions lack effective therapies. Angiogenic growth factors promote contribute to maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating resident endothelial capable self-renewal de novo vessel formation. We hypothesized that ECFCs exist in the developing lung, they during arrested experimental bronchopulmonary dysplasia,...
Background Mesenchymal stem cells (MSC) are self-renewing clonal progenitor of nonhematopoietic tissues that exhibit a marked tropism to wounds and tumors. The authors' studies aimed at exploring how local anesthetics would affect MSC biology. Methods Proliferation, colony formation, in vitro wound healing, bone differentiation assays culture-expanded bone-marrow-derived murine were performed the presence increasing concentrations lidocaine, ropivacaine, bupivacaine. Cytotoxicity was...
Lung hypoplasia and persistent pulmonary hypertension of the newborn limit survival in congenital diaphragmatic hernia (CDH). Unlike other diseases resulting newborn, infants with CDH are refractory to inhaled nitric oxide (NO). Nitric mediates vasodilatation at birth part via cyclic GMP production. Phosphodiesterase type 5 (PDE5) limits effects NO by inactivation GMP. Because limited success postnatal management CDH, we hypothesized that antenatal PDE5 inhibition would attenuate artery...
Functional closure of the human ductus arteriosus (DA) is initiated within minutes birth by O2 constriction. It occurs an incompletely understood mechanism that intrinsic to DA smooth muscle cell (DASMC). We hypothesized alters function sensor (the mitochondrial electron transport chain, ETC) thereby increasing production a diffusible redox-mediator (H2O2), thus triggering effector (inhibition DASMC voltage-gated K+ channels, Kv). constriction was evaluated in 26 DAs (12 female, aged 9+/-2...