The Immature Heart: The Roles of Bone Marrow Stromal Stem Cells in Growth and Myocardial Repair

Studies have shown that adult bone marrow derived stem cells (MSCs) can participate in repair of myocardial injury in adult hearts, as well as in cardiac growth during fetal development in utero. Yet, no studies have evaluated the role of MSCs with respect to normal growth or tissue repair in immature hearts after birth. The present study examines whether MSCs may participate in the myocardial growth and injury in the post-natal immature hearts. MSCs were isolated from adult Lewis rats and labeled with Lac-Z gene using retroviral vectors. These MSCs were injected systemically into groups of neonatal (NB=2days-old), immature (B=30days-old) and adult (A=>3months-old) isogeneic Lewis rats. Additionally, left coronary artery ligation was carried out in subgroups of immature (BL) and adult (AL) rats one week after MSCs injection. The hearts were harvested serially from 2-days to 6-weeks, stained with X-Gal for labeled MSCs. Cardiomyocyte phenotypic expression was evaluated by immunohistological staining for Troponin I-C and Connexin-43. Labeled MSCs were found to home into the bone marrow in all rats of different developmental stages. They could be recruited from bone marrow into the infarcted site of myocardium only in groups AL and BL. They were also capable of differentiating into cardiomyocyte phenotype after myocardial injury. In contrast to that reported in the developing fetus, MSCs did not appear to contribute to the growth of non-injured hearts after birth. However, they can be recruited from the bone marrow and regenerate damaged myocardium both in the adult and in the immature hearts

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Cardiac tissue engineering and regeneration using cell-based therapy

Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineerin

Neurophysiological indices of perceptual object priming in the absence of explicit recognition memory

The aim of this study was to identify ERP correlates of perceptual object priming that are insensitive to factors affecting explicit, episodic memory. EEG was recorded from 21 participants while they performed a visual object recognition test on a combination of unstudied items and old items that were previously encountered during either a ‘deep’ or ‘shallow’ levels-of-processing (LOP) study task. The results demonstrated a midline P150 old/new effect which was sensitive only to objects’ old/new status and not to the accuracy of recognition responses to old items, or to the LOP manipulation. Similar outcomes were observed for the subsequent P200 and N400 effects, the former of which had a parietal scalp maximum and the latter, a broadly distributed topography. In addition an LPC old/new effect typical of those reported in past ERP recognition studies was observed. These outcomes support the proposal that the P150 effect is reflective of perceptual object priming and moreover, provide novel evidence that this and the P200 effect are independent of explicit recognition memory process(es)

Electrophysiological correlates of perceptual auditory priming without explicit recognition memory

The aim of this study was to identify an event-related potential (ERP correlate) of perceptual auditory priming using a method that can dissociate it from explicit memory similar to Rugg et al. (1998). EEG was recorded during performance of an auditory word recognition test, where 17 participants discriminated "old" from "new" aural words, encoded using either a "deep" or "shallow" levels-of-processing (LOP) study task. A right-lateralized P200 effect was modulated by words' old/new status but not by accuracy of recognition or LOP manipulation. Because this effect was driven by simple repetition rather than factors known to influence episodic recognition memory, a "bottom-up" perceptual priming function was inferred which was substantiated by its early temporal appearance. A similar ERP amplitude modulation was evident across a broader topographical region during the subsequent N400 time interval. Conversely the late posterior component (LPC; 500-800 ms) for deeply-encoded, correctly-recognized words was of higher amplitude than LPCs for shallowly-encoded and new words, consistent with proposals that this ERP component indexes episodic memory. To our knowledge this is the first report of an ERP correlate of auditory perceptual priming dissociated from explicit episodic memory