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Objectives: Although critical in animal and human development and pathology, a measurement of the quantitative expression of 5-HTR serotonin receptors on animal or human valvular tissues has never been performed., Methods: Quantification of the most frequent 5-HTRs reported as being present in human peripheral tissue was performed using radiolabeled agonists/antagonists. A membrane protein extract from normal human valves (aortic/mitral/tricuspid and some pulmonary) and associated diseased left myocardium, all unusable in clinics, were obtained from the Homograft bank., Results: We analyzed 5-HT 1A R/5-HT 1B/D R/5-HT 2A R/5-HT 2B R/5-HT 2C R/5-HT 4 R/5-HT 7 R from 28 hearts. We confirmed the presence of tissue and measured the quantitative content for respective proteins in femtomol/mg of protein extracts: for 5-HT 2A R (35.9+/-0.7), 5-HT 2B R (28.8+/-1.3) but also a newly observed and robust expression for 5-HT 4 R (38+/-4.2). We identified one, 5-HT 1A Rs (4.9+/-0.3), and the possible expression, but at a very low level, of previously reported 5-HT 1B/D Rs (1.3+/-0.5) as well as the new 5-HT 7 Rs (3.5+/0.1) and 5-HT 2C Rs (1.2+/-0.1). Interestingly, by using univariate analysis, we were able to observe many correlations between the different 5-HTR levels of expression especially between 5-HT 1A R/5-HT 1B/D R and also between 5-HT 4 R/5-HT 7 R, but none were observed between 5-HT 2A R and 5-HT 2B R. Using multivariate analyses for a specific 5-HTR level of expression, after adjustment for implantation sites and other 5-HTRs, we found that 5-HT 1A R was correlated with 5-HT 1B/D R;5-HT 4 R with 5-HT 7 R and 5-HT 1A R;5-HT 2B R with 5-HT 2A R only. For 5-HT 2 C, no correlation was observed., Conclusion: 5-HT 2A R/5-HT 2B R and 5-HT 4 R were all observed to have a high and equal level of expression on human valves, but that of 5-HT 1A R was more limited. Since these non-5-HT 2 Rs are coupled with different G-proteins, with specific signaling, theoretically they may control the main 5-HT 2 R signaling (i.e., PLC/DAG-PKC-ERK/Ras/Src signaling) involved in valvular fibrosis and degeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schussler, Maroteaux, Jashari, Falcoz, Alifano, Lecarpentier and Launay.)

Background: There is mounting evidence to suggest that the heart has regenerative potential in the event of myocardial injury. Recent studies have shown that a resident population of cardiac progenitor cells (CPCs) in the heart contains both vasculogenic and myogenic lineages. CPCs are able to migrate to the site of injury in the heart for participation in the healing process. The resident CPCs in the heart may also be activated through outside pharmacological intervention to promote their participation in the intrinsic repair process. In the light of these characteristics, CPCs provide a logical source for the heart cell therapy. During the regenerative cardiac process, stem cell niches (a specialised environment surrounding stem cells) provide crucial support needed for their maintenance., Discussion: Compromised niche function may lead to the selection of stem cells that no longer depend on self-renewal factors produced by its environment. The objective of stem cell transplantation associated with tissue-engineered approaches is to create a new modality in the treatment of heart failure. The use of efficient scaffolds will aid to re-establish a favourable microenvironment for stem cell survival, multiplication, differentiation and function. Cardiac tissue engineering using natural and/or synthetic materials in this regard provides a novel possibility in cardiovascular therapeutics.

Myocardial repair using stem-cell therapy has become a promising therapeutic tool. However, many questions concerning a precise functional integration of injected cells remain unanswered. The use of cardiac pre-committed cells may improve integration, as these cells may complete their differentiation in the myocardium reducing fibrosis and restoring muscle function. We have previously demonstrated that electrostimulation (ES) induces cardiomyocyte pre-commitment of fibroblasts in vitro and is an effective alternative to cytokine-induced differentiation. In this study, we evaluated the effects of long term electrostimulation on human mesenchymal stem cells (hMSCs). ES induced both morphological and biochemical changes in hMSCs resulting in a shift toward a striated muscle cell phenotype expressing cardiac specific markers. This partially differentiated phenotype might allow a gradual, ongoing differentiation within the cardiac environment, providing time for both myocardial regeneration and electro-mechanical integration, and convey potential advantages in clinical applications.

Endothelial progenitor cells (EPCs) have significant therapeutic potential. However, the low quantity of such cells available from bone marrow and their limited capacity to proliferate in culture make their use difficult. Here, we present the first definitive demonstration of the presence of true EPCs in murine fetal liver capable of forming blood vessels in vivo connected to the host's vasculature after transplantation. This population is particularly interesting because it can be obtained at high yield and has a high angiogenic capacity as compared with bone marrow-derived EPCs. The EPC capacity is contained within the CD31+Sca1+ cell subset. We demonstrate that these cells are dependent for survival and proliferation on a feeder cell monolayer derived from the fetal liver. In addition, we describe a novel and easy method for the isolation and ex vivo proliferation of these EPCs. Finally, we used gene expression profiling and tandem mass spectrometry proteomics to examine the fetal liver endothelial progenitors and the feeder cells to identify possible proangiogenic growth factor and endothelial differentiation-associated genes.