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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]

We recently reported that the nonclassical HLA class I molecule HLA-G was expressed in the endomyocardial biopsies and sera of 16% of heart transplant patients studied. The aim of the present report is to identify cells that may be responsible for HLA-G protein expression during the allogeneic reaction. Carrying out mixed lymphocyte cultures in which the responder cell population was depleted either in CD[4.sup.+] or CD[8.sup.+] T cells, we found that soluble HLA-G5 protein but not the membrane-bound HLA-G isoform was secreted by allo-specific CD4+ T cells from the responder population, which suppressed the allogeneic proliferative T cell response. This inhibition may be reversed by adding the anti-HLA-G 87G antibody to a mixed lymphocyte culture. That may indicate a previously uncharacterized regulatory mechanism of CD4+ T cell proliferative response.

OBJECTIVES Ventricular constraint devices made of polyester and nitinol have been used to treat heart failure patients. Long-term follow-up has not demonstrated significant benefits, probably due to the lack of effects on myocardial tissue and to the risk of diastolic dysfunction. The goal of this experimental study is to improve ventricular constraint therapy by associating stem cell intrainfarct implantation and a cell-seeded collagen scaffold as an interface between the constraint device and the epicardium. METHODS In a sheep ischaemic model, three study groups were created: Group 1: coronary occlusion without treatment (control group). Group 2: postinfarct ventricular constraint using a polyester device (Acorn CorCap). Group 3: postinfarct treatment with stem cells associated with collagen matrix and the polyester device. Autologous adipose mesenchymal stem cells cultured in hypoxic conditions were injected into the infarct and seeded into the collagen matrix. RESULTS At 3 months, echocardiography showed the limitation of left ventricular end-diastolic volume in animals both treated with constraint devices alone and associated with stem cells/collagen. In Group 3 (stem cell + collagen treatment), significant improvements were found in ejection fraction (EF) and diastolic function evaluated by Doppler-derived mitral deceleration time. In this group, histology showed a reduction of infarct size, with focuses of angiogenesis and minimal fibrosis interface between CorCap and the epicardium due to the interposition of the collagen matrix. CONCLUSIONS Myocardial infarction treated with stem cells associated with a collagen matrix and ventricular constraint device improves systolic and diastolic function, reducing adverse remodelling and fibrosis. The application of bioactive molecules and the recent development of nanobiotechnologies should open the door for the creation of a new semi-degradable ventricular support bioprosthesis, capable of controlled stability or degradation in response to physiological conditions of the left or right heart. [ABSTRACT FROM PUBLISHER]

Adenosine and inosine are both key intracellular energy substrates for nucleotide synthesis by salvage pathways, especially during ischemic stress conditions. Additionally they both possess cell protective and cell repair properties. The objective of this study is to detect potential advantages of the combination of adenosine and inosine versus each drug alone, in terms of ventricular function, infarct size reduction and angiogenesis. Myocardial ischemia was created in rodents and treated with adenosine, inosine or their combination. Results of experiments showed that the combination of both drugs significantly reduced infarct size and improved myocardial angiogenesis and ventricular function. The two compounds, while chemically similar, use different intracellular pathways, allowing for complementary biological activities without overlapping. The drug combination at specific 1 : 5 adenosine : inosine dose ratio demonstrated positive cardiologic effects, deserving further evaluation as an adjunct to reperfusion techniques during and after acute coronary syndrome. The association of adenosine and inosine may contribute to reduce myocardial infarction morbidity and mortality rates. [ABSTRACT FROM AUTHOR]

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.