Commentary on: "Tissue engineering: How to build a heart"

Nessun Abstrac

Stem cell populations in the heart and the role of Isl1 positive cells

Cardiac progenitor cells are multipotent stem cells isolated from both embryonic and adult hearts in several species and are able to differentiate at least into smooth muscle cells, endothelial cells and cardiomyocytes. The embryonic origin of these cells has not yet been demonstrated, but it has been suggested that these cells may derive from the first and secondary heart fields and from the neural crest. In the last decade, two diffe-rent populations of cardiac progenitor or stem cells have been identified and isolated, i.e., the Islet1 positive (Isl1+) and c-Kit positive (c-Kit+)/Stem Cell Antigen-1 positive (Sca-1+) cells. Until 2012, these two populations have been considered two separate entities with different roles and a different origin, but new evidence now suggests a con-nection between the two populations and that the two populations may represent two subpopulations of a unique pool of cardiac stem cells, derived from a common immature primitive cell. To find a common consensus on this concept is very important in furthe-ring the application of stem cells to cardiac tissue engineering

MicroRNA and Cardiac Stem Cell Therapy

Cardiac Progenitor Cells (CPCs) are multipotent cells of the myocardium. They are located inside niches of the heart muscle, can be isolated, characterized and used for cardiac regeneration in stem cell therapy. Actually, CPCs may be isolated by tissue digestion with or without cell sorting, but it is difficult to achieve the maximum level of differentiation when these cells are implanted into a damaged myocardium. The knowledge recently acquired on small molecules of non-coding RNAs, microRNA (miRNA), may improve the use of these cells in stem cell therapy. In fact, these small molecules may be attached to devices or adminstered as they are or in combination with nanoparticles in order to drive the correct differentiation of stem cells. Regarding heart regeneration, we can acquire knowledge from the role of miRNAs in heart development and use it to reprogram CPCs to gain the correct three-dimensional structure of the cardiac muscle

Advances and Perspectives of H2 Production from NH3 Decomposition in Membrane Reactors

Hydrogen is often regarded as an ideal energy carrier. Its use in energy conversion devices does in fact not produce any pollutants. However, due to challenges related to its transportation and storage, liquid hydrogen carriers are being investigated. Among the liquid hydrogen carriers, ammonia is considered very promising because it is easy to store and transport, and its conversion to hydrogen has only nitrogen as a byproduct. This work focuses on a review of the latest results of studies dealing with ammonia decomposition for hydrogen production. After a general introduction to the topic, this review specifically focuses on works presenting results of membrane reactors for ammonia decomposition, particularly describing the different reactor configurations and operating conditions, membrane properties, catalysts, and purification steps that are required to achieve pure hydrogen for fuel cell applications

Extracellular Vesicles: Delivery Vehicles of Myokines

Movement and regular physical activity are two important factors that help the human body prevent, reduce and treat different chronic diseases such as obesity, type 2 diabetes, heart diseases, hypertension, sarcopenia, cachexia and cancer. During exercise, several tissues release molecules into the blood stream, and are able to mediate beneficial effects throughout the whole body. In particular, contracting skeletal muscle cells have the capacity to communicate with other organs through the release of humoral factors that play an important role in the mechanisms of adaptation to physical exercise. These muscle-derived factors, today recognized as myokines, act as endocrine and paracrine hormones. Moreover, exercise may stimulate the release of small membranous vesicles into circulation, whose composition is influenced by the same exercise. Combining the two hypotheses, these molecules related to exercise, named exer-kines, might be secreted from muscle cells inside small vesicles (nanovesicles). These could act as messengers in tissue cross talk during physical exercise. Thanks to their ability to deliver useful molecules (such as proteins and miRNA) in both physiological and pathological conditions, extracellular vesicles can be thought of as promising candidates for potential therapeutic and diagnostic applications for several diseases

Acute change of titin at mid-sarcomere remains despite 8 wk of plyometric training.

Purpose: The purpose of this study was to investigate skeletal muscle changes induced by an acute bout of plyometric exercise (PlyEx) both before and after PlyEx training, to understand if titin is affected differently after PlyEx training. Methods: Healthy untrained individuals (N=11) completed the 1stPlyEx (10x10 squat-jumps, 1min rest). Thereafter, 6 subjects completed 8 weeks of PlyEx, while 5 controls abstained from any jumping activity. Seven days after the last training session all subjects completed the 2ndPlyEx. Blood samples were collected before, 6 hours and 1, 2, 3 and 4 days after each acute bout of PlyEx, and muscle biopsies 4 days before and 3 days after each acute bout of PlyEx. Results: The 1stPlyEx induced an increase in circulating myoglobin concentration. Muscle sample analysis revealed Z-disk streaming, a stretch or a fragmentation of titin (immunogold), and increased calpain-3 autolysis. After training, 2ndPlyEx did not induce Z-disk streaming, or calpain-3 activation. The previously observed post-1stPlyEx positional change of the titin c-terminus was still present pre-2ndPlyEx, in all trained and all control subjects. Only 2 controls presented with Z-disk streaming after 2ndPlyEx, while calpain-3 activation was absent in all controls. Discussion: Eccentric explosive exercise induced a stretch or fragmentation of titin, which presented as a positional change of the c-terminus. Calpain-3 activation does not occur when titin is already stretched before explosive jumping. Enzymatic digestion results in titin fragmentation, but since an increase in calpain-3 autolysis was visible only after the 1stPlyEx acute bout, fragmentation cannot explain the prolonged positional change

Molecular Mechanism of DNA Topoisomerase I-Dependent rDNA Silencing: Sir2p Recruitment at Ribosomal Genes

Saccharomyces cerevisiae sir2Δ or top1Δ mutants exhibit similar phenotypes involving ribosomal DNA, including (i) loss of transcriptional silencing, resulting in non-coding RNA hyperproduction from cryptic RNA polymerase II promoters; (ii) alterations in recombination; and (iii) a general increase in histone acetylation. Given the distinct enzymatic activities of Sir2 and Top1 proteins, a histone deacetylase and a DNA topoisomerase, respectively, we investigated whether genetic and/or physical interactions between the two proteins could explain the shared ribosomal RNA genes (rDNA) phenotypes. We employed an approach of complementing top1Δ cells with yeast, human, truncated, and chimeric yeast/human TOP1 constructs and of assessing the extent of non-coding RNA silencing and histone H4K16 deacetylation. Our findings demonstrate that residues 115–125 within the yeast Top1p N-terminal domain are required for the complementation of the top1Δ rDNA phenotypes. In chromatin immunoprecipitation and co-immunoprecipitation experiments, we further demonstrate the physical interaction between Top1p and Sir2p. Our genetic and biochemical studies support a model whereby Top1p recruits Sir2p to the rDNA and clarifies a structural role of DNA topoisomerase I in the epigenetic regulation of rDNA, independent of its known catalytic activity