Single-Cell RNA Sequencing to Guide Autologous Preterm Cord Mesenchymal Stromal Cell-Therapy.

Rationale: The chronic lung disease bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity (<28 weeks of gestation). Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an opportunity for autologous cell-therapy, as UC-MSCs have been shown to improve lung function and structure in experimental BPD. However, characterization and repair capacity of UC-MSCs derived from donors with pregnancy-related complications associated with prematurity remain unexplored.

Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells.

The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD.

Single-Cell RNA Sequencing-Based Characterization of Resident Lung Mesenchymal Stromal Cells in Bronchopulmonary Dysplasia.

Late lung development is a period of alveolar and microvascular formation, which is pivotal in ensuring sufficient and effective gas exchange. Defects in late lung development manifest in premature infants as a chronic lung disease named bronchopulmonary dysplasia (BPD). Numerous studies demonstrated the therapeutic properties of exogenous bone marrow and umbilical cord-derived mesenchymal stromal cells (MSCs) in experimental BPD.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles for Neonatal Lung Disease: Tiny Particles, Major Promise, Rigorous Requirements for Clinical Translation.

Extreme preterm birth disrupts late lung development and puts newborns at risk of developing chronic lung disease, known as bronchopulmonary dysplasia (BPD). BPD can be associated with life-long complications, and currently no effective treatment is available. Cell therapies are entering the clinics to curb complications of extreme preterm birth with several clinical trials testing the feasibility, safety and efficacy of mesenchymal stromal cells (MSCs).

Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage.

During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development 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 as development.

Complementary Effect of Maternal Sildenafil and Fetal Tracheal Occlusion Improves Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia.

Objective: To evaluate the effect of combining antenatal sildenafil with fetal tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH).

Background: Although antenatal sildenafil administration rescues vascular abnormalities in lungs of fetal rabbits with CDH, it only partially improves airway morphometry. We hypothesized that we could additionally stimulate lung growth by combining this medical treatment with fetal TO.

Characterization of the innate immune response in a novel murine model mimicking bronchopulmonary dysplasia.

Background: Bronchopulmonary dysplasia (BPD), the most common complication of prematurity, arises from various factors that compromise lung development, including oxygen and inflammation. Hyperoxia has been used to mimic the disease in newborn rodents. The use of a second hit to induce systemic inflammation has been suggested as an added strategy to better mimic the inflammatory aspect of BPD.

Simvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbits.

Background: Bronchopulmonary dysplasia (BPD) remains a frequent complication following preterm birth, affecting respiratory health throughout life. Transcriptome analysis in a preterm rabbit model for BPD revealed dysregulation of key genes for inflammation, vascular growth and lung development in animals exposed to hyperoxia, which could be prevented by simvastatin.

Methods: Preterm rabbits were randomized to either normoxia (21% O) or hyperoxia (95% O) and within each condition to treatment with 5 mg/kg simvastatin daily or control.

Nanotherapies for micropreemies: Stem cells and the secretome in bronchopulmonary dysplasia.

Improved survival of extreme preterm infants has made the task of protecting the ever more immature lung from injury more challenging. As a consequence, the incidence of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, has remained unchanged. The multifactorial disease pathogenesis of BPD - including amongst others inflammation, oxidative stress and excessive lung stretch - adds further complexity to finding effective therapies that would prevent lung injury and promote lung growth.

Upregulation of Vascular Endothelial Growth Factor in Amniotic Fluid Stem Cells Enhances Their Potential to Attenuate Lung Injury in a Preterm Rabbit Model of Bronchopulmonary Dysplasia.

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects extremely preterm infants and remains - despite improvements in neonatal intensive care - a major cause of neonatal mortality and morbidity. Cell-therapeutic strategies employing mesenchymal stem cells (MSC) have been shown to modulate lung development in BPD models.

Objective: Herein, we evaluate the potential of human amniotic fluid (hAF)-SC and hAF-SC with upregulated expression of vascular endothelial growth factor (VEGF) as cell-therapeutic agents for BPD.

The amniotic fluid as a source of mesenchymal stem cells with lung-specific characteristics.

The amniotic fluid is a clinically accessible source of mesenchymal stem cells (AF-MSC) during gestation, which enables autologous cellular therapy for perinatal disorders. The origin of AF-MSC remains elusive: renal and neuronal progenitors have been isolated from the AF-MSC pool, yet no cells with pulmonary characteristics. We analyzed gene expression of pulmonary and renal markers of 212 clonal lines of AF-MSC isolated from amniocentesis samples.

Modulation of the Early Host Response to Electrospun Polylactic Acid Matrices by Mesenchymal Stem Cells from the Amniotic Fluid.

Purpose:  The reconstruction of congenital diaphragmatic hernia or other congenital soft tissue defects often requires implants. These can be either degradable or permanent, each having their advantages. Whatever type is being used, the host response induced by implants plays a crucial role to determine the outcome.

Preclinical evaluation of cell-based strategies to prevent or treat bronchopulmonary dysplasia in animal models: a systematic review.

Unlabelled: Bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity as no effective treatment is available to date. This calls for the exploration of new therapeutic options like cell therapy, which is already effective for various human (lung) disorders. We systematically searched the MEDLINE, Embase, and Web of Science databases from the earliest date till January 2017 and included original studies on the perinatal use of cell-based therapies (i.

Proton-pump inhibitor omeprazole attenuates hyperoxia induced lung injury.

Background: The administration of supplemental oxygen to treat ventilatory insufficiency may lead to the formation of reactive oxygen species and subsequent tissue damage. Cytochrome P4501A1 (CYP1A1) can modulate hyperoxic lung injury by a currently unknown mechanism. Our objective was to evaluate the effect of administration of omeprazole on the induction of CYP1A1 and its influence on hyperoxic lung injury in an established preterm rabbit model.

Airway tissue engineering for congenital laryngotracheal disease.

Regenerative medicine offers hope of a sustainable solution for severe airway disease by the creation of functional, immunocompatible organ replacements. When considering fetuses and newborns, there is a specific spectrum of airway pathologies that could benefit from cell therapy and tissue engineering applications. While hypoplastic lungs associated with congenital diaphragmatic hernia (CDH) could benefit from cellular based treatments aimed at ameliorating lung function, patients with upper airway obstruction could take advantage from a de novo tissue engineering approach.

Evaluating Alternative Materials for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse: A Comparison of the In Vivo Response to Meshes Implanted in Rabbits.

Purpose: Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation.

Materials And Methods: Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes.

Safe and effective cryopreservation methods for long-term storage of human-amniotic-fluid-derived stem cells.

Objectives: Stem cells (SCs) can be isolated from amniotic fluid (AF) for a variety of perinatal applications. In view of this, we compared different cryopreservation protocols for these AFSCs.

Methods: We screened seven freezing and thawing protocols using two well-established human AFSC lines: freezing protocol 1 (FP1), 10% dimethyl sulfoxide (DMSO); FP2, 2.

Medical and regenerative solutions for congenital diaphragmatic hernia: a perinatal perspective.

In the EU-27, 2,100 babies with congenital diaphragmatic hernia (CDH) are born annually. CDH is fatal in 30% of them. Experimental fetal surgery in severe cases results in a survival rate of 50 to 60% at its best.

Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.

GABAergic interneurons mainly originate in the medial ganglionic eminence (MGE) of the embryonic ventral telencephalon (VT) and migrate tangentially to the cortex, guided by membrane-bound and secreted factors. We found that Sip1 (Zfhx1b, Zeb2), a transcription factor enriched in migrating cortical interneurons, is required for their proper differentiation and correct guidance. The majority of Sip1 knockout interneurons fail to migrate to the neocortex and stall in the VT.

Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in TGFβ/BMP signaling in vivo.

Signaling by the many ligands of the TGFβ family strongly converges towards only five receptor-activated, intracellular Smad proteins, which fall into two classes i.e. Smad2/3 and Smad1/5/8, respectively.