Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

<p>Abstract</p> <p>Background</p> <p>Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity.</p> <p>Results</p> <p>After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G₁phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation.</p> <p>Conclusion</p> <p>Physiologic oxygen tension during <it>in vitro </it>culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.</p

Pulmonary artery banding in dilative cardiomyopathy of young children: review and protocol based on the current knowledge

Dilated cardiomyopathy (DCM) is a leading cause of cardiac death in children. Current therapeutic strategies are focused on improving symptoms of congestive heart failure (CHF); the potentials of cardiac regeneration especially in infants and young children are neglected in particular when DCM is classified as "end-stage". Heart transplantation (HTx) serves as the only life-saving option, despite is palliative character with limited survival time. Therapeutic alternatives are strongly needed, but already existing though less used; presupposed, that cardiac dysfunction and its treatment are not reduced to the four components of heart rate (rhythm), myocardial contractility, preload and afterload. A paradigm shift in the treatment of pediatric heart failure can be achieved by modifying ventricular afterload with improving contra-lateral ventricular function. Adverse ventricular-ventricular interactions (VVI) have the potential to harness them for therapeutic benefit. Surgical placement of a pulmonary artery banding (PAB) utilized in infants and young children with LV-DCM and preserved RV function are able to improve LV function via VVI; it is hypothesized, that functional recovery can be achieved in almost 80% especially of infants with LV-DCM despite criteria for listing to orthotopic HTx. The review summarizes details of the current perioperative treatment enabling each pediatric heart center to utilize rPAB as a strategy for functional recovery, even in centers without the option for Htx. Of course, future studies are needed to delineate the geometrical, temporal and molecular mechanisms of PA-banding-induced ventricular crosstalk and to examine their potential modulation through mechanical, electrophysiological and pharmacological interventions, but our patients are born, now

Inadvertent intravenous administration of maternal breast milk in a six-week-old infant: a case report and review of the literature

BACKGROUND: Accidental intravenous administration of an enteral feeding can be fatal or cause complications such as sepsis, acute respiratory and circulatory failure, acute renal failure, hepatic insufficiency, coagulation disorders and severe permanent neurological sequelae. These “wrong route” errors are possible due to compatible connections between enteral feeding systems and intravascular infusion catheters. CASE PRESENTATION: We report a six-week-old male infant who received a 5 ml intravenous infusion of breast milk. Within five minutes of administration the child developed tachycardia and tachypnea, accompanied by a sudden decrease in oxygen saturation on pulse oximetry to 69%. The infant received supplemental oxygen via nasal cannula and was transferred to the pediatric intensive care unit. Broad-spectrum antibiotics were administered for 48 hours. Vital signs returned to normal within a few hours. Neurological follow-up through 3 years did not reveal any neurodevelopmental abnormalities. CONCLUSION: Development of specific enteral feeding connections, which are incompatible with intravascular catheter connections, is needed urgently to prevent a misconnection with potential morbidity or mortality of children

Transcatheter creation of a de novo communication across an extracardiac Fontan conduit for catheter ablation of a "left-sided" accessory pathway

WOS: 000330809800010PubMed ID: 24253073Extracardiac polytetrafluoroethylene (PTFE) conduits are often used in modified Fontan procedures for separating systemic and pulmonary circulations in morphological and functional single ventricles [1]. However, most arrhythmia substrates of congenital and acquired supraventricular tachycardias will then be located ‘‘left-sided’’ across the extracardiac conduit. Remote magnetic navigation not only may facilitate a retrograde approach, but may also fail to reach the arrhythmia substrate [2]. Hybrid intervention consisting of transcatheter ablation via a sternotomy approach and atriotomy incision [3] as well as catheter ablation via direct transthoracic percutaneous access [4] have been described, but appear to be associated with frequent complications. An antegrade approach via femoral access requires special techniques for traversing the stiff PTFE material, the pericardial space and the atrial muscular wall. This is the first report that describes a modified transseptal puncture technique using no more than mechanical force [5] for successful catheter ablation across an extracardiac PTFE Fontan conduit

Rare Case of an Adult With Double-Chambered Left VentricleNovel Teaching Points

The rare case of an adult with a double-chambered left ventricle was revealed using multimodality imaging using echocardiography and cardiac magnetic resonance imaging in a 38-year-old asymptomatic male patient. The congenital malformation was dominated by a second, coarsely trabeculated muscular shelf dividing the left ventricle into 2 chambers without signs for left ventricular inflow or outflow tract obstruction. The partition wall did not show any signs for intramyocardial fibrosis in late gadolinium enhancement cardiovascular magnetic resonance imaging. Flow measurements excluded a relevant intracardial shunt across the additive perimembranous ventricular septal defect. There were no signs for global right and left ventricular dysfunction with left and right ventricular volumes and ejection fraction within normal limits. A conservative approach was recommended. In summary, we are able to present the case of an adult with a double-chambered left ventricle with a second muscular “septum” partially dividing the left ventricular cavity without causing a relevant impact on cardiac function or clinical signs for heart failure. Résumé: Le cas rare d’un adulte présentant un ventricule gauche à double chambre a été révélé par une imagerie multimodale utilisant l’échocardiographie et l’imagerie par résonnance magnétique cardiaque chez un homme asymptomatique de 38 ans. La malformation congénitale était dominée par une deuxième bande musculaire grossièrement trabéculaire divisant le ventricule gauche en deux chambres sans signes d’obstruction des chambres d’admission et d’éjection du ventricule gauche. La cloison de partition ne montrait aucun signe de fibrose intramyocardique à l’imagerie par résonnance magnétique cardiovasculaire avec rehaussement tardif au gadolinium. Les mesures du débit ont exclu un shunt intracardiaque significatif à travers le défaut septal ventriculaire transmembranaire supplémentaire. Il n’y avait pas de signe de dysfonction ventriculaire droite et gauche globale, les volumes ventriculaires gauche et droit et la fraction d’éjection étant dans les limites normales. Une approche conservatrice a été recommandée. En résumé, nous pouvons présenter le cas d’un adulte porteur d’un ventricule à double chambre avec une deuxième « cloison » musculaire divisant partiellement la cavité ventriculaire gauche sans causer d’effet notable sur la fonction cardiaque ou de signes cliniques d’insuffisance cardiaque