From cord to caudate: characterizing umbilical cord blood stem cells and their paracrine interactions with the injured brain.

Stem cells are proving to be a promising therapy for a wide range of pediatric disorders, from neonatal hypoxic-ischemic encephalopathy to pediatric leukemia. Owing to their low immunogenicity and ease of availability, umbilical cord blood (UCB) progenitor cells are increasingly replacing fetal- and adult-derived cells in therapeutic settings. Multiple environmental and demographic factors affect the number and type of stem cells extracted from UCB, and these differences have been associated with disparities in outcomes after transplantation. To avoid variations in efficacy, as well as the potential adverse effects of stem cell transplantation, evaluation of the stem cell secretome is critical to identify key paracrine signals released by the stem cells that could be used to provide similar neuroprotective effects to stem cell transplantation. This article describes the cell types found in UCB and reviews the available literature surrounding the effects of collection timing and volume, maternal risk factors, delivery characteristics, and neonatal demographics on the cellular composition of UCB. In addition, the current findings regarding the stem cell secretome are discussed to identify factors that could be used to supplement or replace stem cell transplantation in pediatric neuroprotection.

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.

AIM: To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS: Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS: Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION: To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.