Introduction: Nowadays, heart is one of the most demanding organs for imaging procedures. This is related to its irregular shape and complex internal structure. Increased demand for imaging complex cardiac structures has resulted in the development of novel 3D modeling techniques. Not only did the methods of imaging the organs of the living patients developed in recent years, but also new methods of post-mortem analysis. Acquired 3D models have a number of applications, both clinical and educational. Detailed knowledge of the morphology of right ventricular outflow tract (RVOT) is extremely important in terms of cardio-invasive therapeutic procedures. Its significance was noticed during the exploration of the optimal pacing sites in the area of right ventricle. What is more, accurate analysis of the RVOT morphology and spatial structure is also the basis for the treatment of ventricular arrhythmias which foci are located within the outflow tract. The aim of this study was to elaborate the most accurate technique of preparing interior models of the right ventricle and digitizing them to the 3D form. For this purpose we used a silicone molding of the heart cavities with digital photogrammetry.
Objective: This study evaluated the use of novel peptides derived from platelet-derived growth factor (PDGF-BB) as potential wound healing stimulants. One of the compounds (named PDGF2) was subjected for further research after cytotoxicity and proliferation assays on human skin cells. Further investigation included evaluation of: migration and chemotaxis of skin cells, immunological and allergic safety, the transcriptional analyses of adipose-derived stem cells (ASCs) and dermal fibroblasts stimulated with PDGF2, and the use of dorsal skin wound injury model to evaluate the effect of wound healing in mice. Approach: Colorimetric lactate dehydrogenase and tetrazolium assays were used to evaluate the cytotoxicity and the effect on proliferation. PDGF2 effect on migration and chemotaxis was also checked. Immunological safety and allergic potential were evaluated with a lymphocyte activation and basophil activation test. Transcriptional profiles of ASCs and primary fibroblasts were assessed after stimulation with PDGF2. Eight-week-old BALB/c female mice were used for dorsal skin wound injury model. Results: PDGF2 showed low cytotoxicity, pro-proliferative effects on human skin cells, high immunological safety, and accelerated wound healing in mouse model. Furthermore, transcriptomic analysis of ASCs and fibroblasts revealed the activation of processes involved in wound healing and indicated its safety. Innovation: A novel peptide derived from PDGF-BB was proved to be safe drug candidate in wound healing. We also present a multifaceted in vitro model for the initial screening of new compounds that may be potentially useful in wound healing stimulation. Conclusion: The results show that peptide derived from PDGF-BB is a promising drug candidate for wound treatment.
Background: Most studies on regenerative medicine focus on cell-based therapies and transplantations. Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensively investigated in regenerative research. It is known that healing potential decreases with development and developmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerative capacity. Methods: We applied zebularine, a nucleoside inhibitor of DNA methyltransferases, to stimulate the regenerative response in a model of ear pinna injury in mice. Findings: We observed the regeneration of complex tissue that was manifested as improved ear hole repair in mice that received intraperitoneal injections of zebularine. Six weeks after injury, the mean hole area decreased by 83.2 +/- 9.4% in zebularine-treated and by 43.6 +/- 15.4% in control mice (p < 10(-30)). Combined delivery of zebularine and retinoic acid potentiated and accelerated this effect, resulting in complete ear hole closure within three weeks after injury. We found a decrease in DNA methylation and transcriptional activation of neurodevelopmental and pluripotency genes in the regenerating tissues. Interpretation: This study is the first to demonstrate an effective induction of complex tissue regeneration in adult mammals using zebularine. We showed that the synergistic action of an epigenetic drug (zebularine) and a transcriptional activator (retinoic acid) could be effectively utilized to induce the regenerative response, thus delineating a novel pharmacological strategy for regeneration. The strategy was effective in the model of ear pinna regeneration in mice, but zebularine acts on different cell types, therefore, a similar approach can be tested in other tissues and organs. (C) 2019 The Authors. Published by Elsevier B.V.
Background.In cardiology, the paths of the arteries penetrating the septomarginal trabecula (SMT) are especially important.They provide blood supply to the apparatus of the right atrioventricular orifice and often form anastomoses with the system of the right coronary artery.Despite this, only a few publications discuss the morphological aspect of the septomarginal trabecula, and available histological analyses seldom deal with its blood supply.Objectives.The aim of this study was to analyze the vessel structure of the septomarginal trabecula in terms of the variability of the area of the cross-section of the lumen and the muscular layer of the artery. Material and methods.The study was carried out on the material of 50 human hearts from adults of both sexes.The material was divided into 4 morphological types.Histological examinations were conducted by means of classic staining methods.Results.At the initial cross-section of the septomarginal trabecula, the area of the cross-section increased to half of the length of the trabecula, and then it started to decrease.This is connected with the thickening of the inner muscular layer of the artery, which proportionally takes up more area of the cross-section of the whole artery of the SMT.The total area of the cross-section of all vessels in both types examined was also the largest in the middle part of the SMT.Furthermore, the results of this study confirm the presence of a connection between both systems of coronary arteries. Conclusions.As the septomarginal trabecula passes through the lumen of the right ventricle, its arteries become exposed to the influence of the factors which may evoke a biological response from the walls of this vessel, causing the thickening of the muscular layer and, as a result, of the section of the whole artery, in particular its middle part.
Adipose-derived stem cells (ASCs) have become an important research model in regenerative medicine. However, there are controversies regarding the impact of prolonged cell culture on the ASCs phenotype and their differentiation potential. Hence, we studied 10 clinical ASCs replicates from plastic and oncological surgery patients, in six-passage FBS supplemented cultures. We quantified basic mesenchymal cell surface marker transcripts and the encoded proteins after each passage. In parallel, we investigated the differentiation potential of ASCs into chondrocytes, osteocytes and adipocytes. We further determined the effects of FBS supplementation and subsequent deprivation on the whole transcriptome by comprehensive mRNA and miRNA sequencing. Our results show that ASCs maintain differentiation potential and consistent profile of key mesenchymal markers, with apparent expression of distinct isoforms, in long-term cultures. No significant differences were observed between plastic and oncological surgery cohorts. ASCs in FBS supplemented primary cultures are almost committed to mesenchymal lineages as they express key epithelial-mesenchymal transition genes including early mesenchymal markers. Furthermore, combined mRNA/miRNA expression profiling strongly supports a modulatory role for the miR-30 family in the commitment process to mesenchymal lineages. Finally, we propose improvements to existing qPCR based assays that address alternative isoform expression of mesenchymal markers.
Background and aim: Atrial fibrillation (AF) is a common arrhythmia in elderly people, and in many cases it is responsible for stroke or pulmonary embolism. One of the factors facilitating atrial thrombus formation is anatomical morphology of the atria, and especially the appendages. The pharmacological treatment of arrhythmia is generally focused on ventricular rate control. Electrical cardioversion is the preferred treatment method in the majority of clinics but it can occasionally produce the potentially dangerous complication of AF.Methods: A macroscopic study was carried out on 40 (25 male [M], 15 female [F]) human hearts, 18-72 years of age, and a microscopic study in a group of 20 human right atrial appendages (RAA) (M 10, F 10), 18-72 years of age. Only hearts without anomalies were included in the study. Classical anatomical studies and statistic analyses were applied.Results and conclusions: RAA is triangle shaped with a mean area of 2.73 cm(2). Muscle fascicules build the wall of RAA and compose a dense net inside a chamber. Sagittal bundle connecting terminal crest with an apex of RAA was observed in all examined hearts. In microscopic specimens longitudinal and perpendicular fascicles were described.
The observational results of the morphology of the coronary sinus valve are presented in this study. Research was conducted on material consisting of 100 adult human hearts of both sexes from 18 to 87 years of age. Basic morphological types of the examined structure are distiguished and the main traits regarding their histological nature are presented.