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Open in new tab Download slide Open in new tab Download slide OBJECTIVES Prevention of postischaemic ventricular dilatation progressing towards pathological remodelling is necessary to decrease ventricular wall deterioration. Myocardial tissue engineering may play a therapeutic role due to its capacity to replace the extracellular matrix, thereby creating niches for cell homing. In this experimental animal study, a biomimetic cardiopatch was created with elastomeric scaffolds and nanotechnologies. METHODS In an experimental animal study in 18 sheep, a cardiopatch was created with adipose tissue-derived progenitor cells seeded into an engineered bioimplant consisting of 3-dimensional bioabsorbable polycaprolactone scaffolds filled with a peptide hydrogel (PuraMatrix™). This patch was then transplanted to cover infarcted myocardium. Non-absorbable poly(ethyl) acrylate polymer scaffolds were used as controls. RESULTS Fifteen sheep were followed with ultrasound scans at 6 months, including echocardiography scans, tissue Doppler and spectral flow analysis and speckle-tracking imaging, which showed a reduction in longitudinal left ventricular deformation in the cardiopatch-treated group. Magnetic resonance imaging (late gadolinium enhancement) showed reduction of infarct size relative to left ventricular mass in the cardiopatch group versus the controls. Histopathological analysis at 6 months showed that the cardiopatch was fully anchored and integrated to the infarct area with minimal fibrosis interface, thereby promoting angiogenesis and migration of adipose tissue-derived progenitor cells to surrounding tissues. CONCLUSIONS This study shows the feasibility and effectiveness of a cardiopatch grafted onto myocardial infarction scars in an experimental animal model. This treatment decreased fibrosis, limited infarct scar expansion and reduced postischaemic ventricular deformity. A capillary network developed between our scaffold and the heart. The elastomeric cardiopatch seems to have a positive impact on ventricular remodelling and performance in patients with heart failure. [ABSTRACT FROM AUTHOR]

The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously developed a semiresorbable armored prosthesis able to mechanically sustain the neoaorta preventing dilation and to gradually integrate with the PA wall inducing a progressive arterial-like tissue positive remodeling. We also described the mechanisms of growth, remodeling and stress shielding of the reinforced PA through a mathematical model. We sought to demonstrate the biological counterpart and the potential molecular mechanisms underlying this histological and mechanical remodeling. A specific mathematical model was developed to describe mechanical behavior of the PA. Mallory trichrome red staining and immunohistochemistry for MMP-9 were performed to elucidate extracellular matrix remodeling phenomena. Apoptosis and cell proliferation were determined by TUNEL assay and immunohistochemistry for Ki67, respectively. An histological remodeling phenomenon sustained by increased level of MMP-9, augmented cell proliferation and reduced apoptosis in the reinforced PA was demonstrated. The mathematical model predicted the biomechanical behavior subtended by the histological changes of the PA in these settings. Changes in metalloproteinases (MMP-9), cell proliferation and apoptosis are the main actors in the remodeling process occurring after transposition of the PA into systemic regimens. Use of semiresorbable reinforcements might induce a positive remodeling of the PA in the context of Ross operation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2785-2793, 2016. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey. Methods and Results: We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, geographic area, training and full-time researcher status. Specifically, women proved significantly less satisfied than men, disclosed access to fewer resources and less support from mentors (all P<0.05). People working in institutions not located in North America or Northern/Central Europe were significantly less satisfied and disclosed much less support (both P<0.05). Those in training reported limited opportunities for collaboration (P = 0.009), and non-full-time researchers disclosed more limited access to tutors and formal grant writing training (both P<0.05). Conclusions: Several potential biases appear to be present in the way training in cardiovascular research is provided worldwide, including one against women. If confirmed, these data require proactive measures to decrease discriminations and improve the cardiovascular research training quality. [ABSTRACT FROM AUTHOR]

Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopathology and law of physics. It concerns a double lumen disposable tube device that could be adapted to conventional cardiopulmonary bypass (CPB) and/or CAD, for inducing a homogenous, downstream pulsatile perfusion mode with lower energy losses. In this study, the device's prototypes were tested in a simulated conventional pediatric CPB circuit for energy losses and as a left ventricular assist device (LVAD) in ischemic piglets model for endothelial shear stress (ESS) evaluations. In conclusion and according to the study results the pulsatile tube was successfully capable of transforming a conventional CPB and/or CAD steady flow into a pulsatile perfusion mode, with nearly physiologic pulse pressure and lower energy losses. This represents a cost-effective promising method with low mortality and morbidity, especially in fragile cardiac patients. [ABSTRACT FROM AUTHOR]

Background: Cardiac-assist devices for right ventricular failure remain controversial with poor results. This study evaluated a pulsatile cardiac-assist device in an acute right ventricular failure model vs. current therapies.Materials and methods: Pulmonary regurgitation was created in 12 piglets by valve avulsion and external transfixation of 2 pulmonary artery cusps suspended to the pulmonary arterial wall. The piglets were divided into 2 treatment groups: a pulsatile group P and a non-pulsatile group NP. Management started when severe right ventricular failure was observed (48.1 ± 24.5 min). In group P, pulsatile trousers driven by a pneumatic generator were pulsated intermittently at 40 beats·min−1. Group NP was treated with oral tadalafil 1 mg·kg−1, intravenous fluids, and adrenaline 0.3 µg·kg−1. After 1 h of therapy, cardiac output was significantly better in group P than group NP (1 ± 0.2 vs. 0.7 ± 0.2 L·min−1). Mean right ventricular pressure (16 ± 6 vs. 24 ± 2 mm Hg) and pulmonary arterial pressure (22 ± 1 vs. 31 ± 2 mm Hg) were lower in group P. Vascular resistances indices were lower in group P than group NP: pulmonary resistance index was 174 ± 60 vs. 352 ± 118 dyne·sec·cm−5·kg−1; systemic resistance index was 611 ± 70 vs. 1215 ± 315 dyne·sec·cm−5·kg−1. Western-blot analysis showed higher endogenous NO synthase expression in group P pulmonary arteries.Conclusions: The pulsatile suit can be used safely as a noninvasive cardiac-assist device in acute right ventricular failure. This represents a cost-effective nearly physiological method, suitable for adults and children. [ABSTRACT FROM AUTHOR]

Objectives: Large animal experimental models of chronic heart failure (HF) permit repeated invasive assessment of cardiovascular function, and evaluation of new medical or surgical therapies. The existing models however fail to achieve stable and long-term HF. The aim of this study was to create a simple and stable chronic model of HF in goat, using both arteriovenous fistula and weekly intravenous doxorubicin injections.Methods: After a preliminary experiment on four goats receiving weekly 1 to 2 mg/kg of doxorubicin, six adult female goats, having had an arteriovenous fistula without signs or symptoms of heart failure, received weekly two different dosages of doxorubicin for 13 weeks: group A (n = 3) received 0.5 mg/kg and group B (n = 3) received 1 mg/kg. After a three-month period without medication, both groups received again 1 mg/kg for four weeks. Cardiac function was assessed by repeated electrocardiographic and echocardiographic examinations.Results: Four goats died during the medication period (one in group A, three in group B). During the period without medication a stable ventricular hypocontractility with left ventricular dilation was observed. Left ventricular dysfunction was more pronounced in group B, and was associated with clinical symptoms of HF.Conclusions: Arteriovenous fistula alone did not produce HF. Its association with doxorubicin injections provides a simple and stable chronic model of HF. This association allows reduction of the required doxorubicin dose and toxicity in animals and in the environment. Depending of the dose of doxorubicin, it is possible to obtain a model of heart dilatation and ventricular hypokinesia with or without clinical symptoms of HF, with a different mortality. [ABSTRACT FROM AUTHOR]

From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development. [ABSTRACT FROM AUTHOR]

This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like neurons using a natural membrane. The isolation of hMSCs from Wharton's jelly (WJ) was carried out using "explant" and mononuclear cells by the density gradient from umbilical blood and characterized by flow cytometry. hMSCs were seeded in a natural functional biopolymer membrane to produce neurospheres. RT-PCR was performed on hMSCs and neurospheres derived from the umbilical cord. Neural precursor cells were subjected to a standard cholinergic-like neuron differentiation protocol. Dissociated neurospheres, neural precursor cells, and cholinergic-like neurons were characterized by immunocytochemistry. hMSCs were CD73+, CD90+, CD105+, CD34- and CD45- and demonstrated the trilineage differentiation. Neurospheres and their isolated cells were nestin-positive and expressed NESTIN, MAP2, ßIII-TUBULIN, GFAP genes. Neural precursor cells that were differentiated in cholinergic-like neurons expressed ßIII-TUBULIN protein and choline acetyltransferase enzyme. hMSCs seeded on the natural membrane can differentiate into neurospheres, obtaining neural precursor cells without growth factors or gene transfection before cholinergic phenotype differentiation. [ABSTRACT FROM AUTHOR]

A challenge in contractile restoration of myocardial scars is one of the principal aims in cardiovascular surgery. Recently, a new potent biological tool used within healing processes is represented by exosomes derived from mesenchymal stem cells (MSCs). These cells are the well-known extracellular nanovesicles released from cells to facilitate cell function and communication. In this work, a combination of elastomeric membranes and exosomes was obtained and tested as a bioimplant. Mesenchymal stem cells (MSCs) and macrophages were seeded into the scaffold (polycaprolactone) and filled with exosomes derived from MSCs. Cells were tested for proliferation with an MTT test, and for wound healing properties and macrophage polarization by gene expression. Moreover, morphological analyses of their ability to colonize the scaffolds surfaces have been further evaluated. Results confirm that exosomes were easily entrapped onto the surface of the elastomeric scaffolds, increasing the wound healing properties and collagen type I and vitronectin of the MSC, and improving the M2 phenotype of the macrophages, mainly thanks to the increase in miRNA124 and decrease in miRNA 125. We can conclude that the enrichment of elastomeric scaffolds functionalized with exosomes is as an effective strategy to improve myocardial regeneration. [ABSTRACT FROM AUTHOR]

Background: Electrospun fibers have attracted a lot of attention from researchers due to their several characteristics, such as a very thin diameter, three-dimensional topography, large surface area, flexible surface, good mechanical characteristics, suitable for widespread applications. Indeed, electro-spinning offers many benefits, such as great surface-to-volume ratio, adjustable porosity, and the ability of imitating the tissue extra-cellular matrix. Methods: we processed Poly ε-caprolactone (PCL) via electrospinning for the production of bilayered tubular scaffolds for vascular tissue engineering application. Endothelial cells and fibroblasts were seeded into the two side of the scaffolds: endothelial cells onto the inner side composed of PCL/Gelatin fibers able to mimic the inner surface of the vessels, and fibroblasts onto the outer side only exposing PCL fibers. Extracellular matrix production and organization has been performed by means of classical immunofluorescence against collagen type I fibers, Scanning Electron-Microscopy (SEM) has been performed in order to evaluated ultrastructural morphology, gene expression by means gene expression has been performed to evaluate the phenotype of endothelial cells and fibroblasts. Results and conclusion: results confirmed that both cells population are able to conserve their phenotype colonizing the surface supporting the hypothesis that PCL scaffolds based on electrospun fibers should be a good candidate for vascular surgery. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have recently attracted a great deal of interest as they may represent a new biosignaling paradigm. According to the mode of biogenesis, size and composition, two broad categories of EVs have been described, exosomes and microvesicles. EVs have been shown to carry cargoes of signaling proteins, RNA species, DNA and lipids. Once released, their content is selectively taken up by near or distant target cells, influencing their behavior. Exosomes are involved in cell–cell communication in a wide range of embryonic developmental processes and in fetal–maternal communication. In the present review, an outline of the role of EVs in neural development, regeneration and diseases is presented. EVs can act as regulators of normal homeostasis, but they can also promote either neuroinflammation/degeneration or tissue repair in pathological conditions, depending on their content. Since EV molecular cargo constitutes a representation of the origin cell status, EVs can be exploited in the diagnosis of several diseases. Due to their capability to cross the blood–brain barrier (BBB), EVs not only have been suggested for the diagnosis of central nervous system disorders by means of minimally invasive procedures, i.e., "liquid biopsies", but they are also considered attractive tools for targeted drug delivery across the BBB. From the therapeutic perspective, mesenchymal stem cells (MSCs) represent one of the most promising sources of EVs. In particular, the neuroprotective properties of MSCs derived from the dental pulp are here discussed. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease originated in Wuhan, China, in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severe form of the disease is often associated with acute respiratory distress syndrome (ARDS), and most critically ill patients require mechanical ventilation and support in intensive care units. A significant portion of COVID-19 patients also develop complications of the cardiovascular system, primarily acute myocardial injury, arrhythmia, or heart failure. To date, no specific antiviral therapy is available for patients with SARS-CoV-2 infection. Exosomes derived from mesenchymal stem cells (MSCs) are being explored for the management of a number of diseases that currently have limited or no therapeutic options, thanks to their anti-inflammatory, immunomodulatory, and pro-angiogenic properties. Here, we briefly introduce the pathogenesis of SARS-CoV-2 and its implications in the heart and lungs. Next, we describe some of the most significant clinical evidence of the successful use of MSC-derived exosomes in animal models of lung and heart injuries, which might strengthen our hypothesis in terms of their utility for also treating critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Three dimensional (3D) printing, which consists in the conversion of digital images into a 3D physical model, is a promising and versatile field that, over the last decade, has experienced a rapid development in medicine. Cardiovascular medicine, in particular, is one of the fastest growing area for medical 3D printing. In this review, we firstly describe the major steps and the most common technologies used in the 3D printing process, then we present current applications of 3D printing with relevance to the cardiovascular field. The technology is more frequently used for the creation of anatomical 3D models useful for teaching, training, and procedural planning of complex surgical cases, as well as for facilitating communication with patients and their families. However, the most attractive and novel application of 3D printing in the last years is bioprinting, which holds the great potential to solve the ever-increasing crisis of organ shortage. In this review, we then present some of the 3D bioprinting strategies used for fabricating fully functional cardiovascular tissues, including myocardium, heart tissue patches, and heart valves. The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro cardiovascular drug toxicity. Finally, we describe some applications of 3D printing in the development and testing of cardiovascular medical devices, and the current regulatory frameworks that apply to manufacturing and commercialization of 3D printed products. [ABSTRACT FROM AUTHOR]

Exosomes are a subgroup of extracellular vesicles containing a huge number of bioactive molecules. They represent an important means of cell communication, mostly between different cell populations, with the purpose of maintaining tissue homeostasis and coordinating the adaptive response to stress. This type of intercellular communication is important in the cardiovascular field, mainly due to the fact that the heart is a complex multicellular system. Given the growing interest in the role of exosomes in cardiovascular diseases and the numerous studies published in the last few decades, we focused on the most relevant results about exosomes in the cardiovascular filed starting from their characterization, passing through the study of their function, and ending with perspectives for their use in cardiovascular therapies. [ABSTRACT FROM AUTHOR]