Transplantation of Human Umbilical Cord Blood-Derived Cellular Fraction Improves Left Ventricular Function and Remodeling After Myocardial Ischemia/Reperfusion.

Rationale: Human umbilical cord blood (hUCB) contains diverse populations of stem/progenitor cells. Whether hUCB-derived nonhematopoietic cells would induce cardiac repair remains unknown. Objective: To examine whether intramyocardial transplantation of hUCB-derived CD45-Lin- nonhematopoietic cellular fraction after a reperfused myocardial infarction in nonimmunosuppressed rats would improve cardiac function and ameliorate ventricular remodeling. Methods and Results: Nonhematopoietic CD45-Lin- cells were isolated from hUCB. Flow cytometry and quantitative polymerase chain reaction were used to characterize this subpopulation. Age-matched male Fischer 344 rats underwent a 30-minute coronary occlusion followed by reperfusion and 48 hours later received intramyocardial injection of vehicle or hUCB CD45-Lin- cells. After 35 days, compared with vehicle-treated rats, CD45-Lin- cell-treated rats exhibited improved left ventricular function, blunted left ventricular hypertrophy, greater preservation of viable myocardium in the infarct zone, and superior left ventricular remodeling. Mechanistically, hUCB CD45-Lin- cell injection favorably modulated molecular pathways regulating myocardial fibrosis, cardiomyocyte apoptosis, angiogenesis, and inflammation in postinfarct ventricular myocardium. Rare persistent transplanted human cells could be detected at both 4 and 35 days after myocardial infarction. Conclusions: Transplantation of hUCB-derived CD45-Lin- nonhematopoietic cellular subfraction after a reperfused myocardial infarction in nonimmunosuppressed rats ameliorates left ventricular dysfunction and improves remodeling via favorable paracrine modulation of molecular pathways. These findings with human cells in a clinically relevant model of myocardial ischemia/reperfusion in immunocompetent animals may have significant translational implications.Visual Overview: An online visual overview is available for this article.

Neurobehavioral effects in rat pups whose sires were exposed to alcohol.

Developmental neurobehavioral effects associated with maternal exposure to alcohol during pregnancy are well described, but little is known about the effects of paternal exposure prior to conception. Using a quasi-experimental, within-subjects design, neurobehavioral outcomes (reflex acquisition, activity, gait) and cerebral cortical layer thickness were assessed in Sprague-Dawley rat pups from breeding pairs where the sires were exposed to alcohol. Comparisons were made on the basis of the timing of conception relative to alcohol exposure: phase 1 (controls), prior to initiation of alcohol exposure; phase 2, during the period of treatment with 20% alcohol; and phase 3, following cessation of alcohol exposure. Phase 2 and 3 pups were noted to attain negative geotaxis and reflex suspension benchmarks earlier than control pups and to have more difficulty with balance. Phase 3 pups were noted to attain righting reflex earlier than controls. In addition, phase 3 pups demonstrated increased levels of reverse maze activity and a shorter and narrower gait. Brain morphometry revealed thickening of cortical sections I-IV and V-VI resulting in overall cortical enlargement in both phase 2 and 3 pups. Further analysis of phase 2 and 3 subphases based on the presumed stages of the spermatogenic cycle during which sires were exposed to alcohol revealed significant differences in maze activity, reflex acquisition, and gait length. These findings suggest pre-conception male exposure to alcohol may have an effect on the offspring and the extent of the effects may vary with the timing of alcohol exposure relative to conception.