The advanced glycation end-product N -carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes-associated risk and its prevention.

Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs.

Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture.

Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects.

Exosomes isolation protocols: facts and artifacts for cardiac regeneration.

In recent years, exosomes have attracted increasing scientific interest and are no longer considered just as containers for cell waste, but as important mediators of intercellular communication. Among many biomedical research topics, a possible direct role of exosomes in the regenerative medicine field has been underlined in recent studies, including those regarding the so called "paracrine hypothesis". In this perspective, a therapeutic role and/or use of exosomes for tissue regeneration seems to be plausible.

SHOX2 overexpression favors differentiation of embryonic stem cells into cardiac pacemaker cells, improving biological pacing ability.

When pluripotency factors are removed, embryonic stem cells (ESCs) undergo spontaneous differentiation, which, among other lineages, also gives rise to cardiac sublineages, including chamber cardiomyocytes and pacemaker cells. Such heterogeneity complicates the use of ESC-derived heart cells in therapeutic and diagnostic applications. We sought to direct ESCs to differentiate specifically into cardiac pacemaker cells by overexpressing a transcription factor critical for embryonic patterning of the native cardiac pacemaker (the sinoatrial node).

Engineered electrical conduction tract restores conduction in complete heart block: from in vitro to in vivo proof of concept.

Background: Cardiac electrical conduction delays and blocks cause rhythm disturbances such as complete heart block, which can be fatal. Standard of care relies on electronic devices to artificially restore synchrony. We sought to create a new modality for treating these disorders by engineering electrical conduction tracts designed to propagate electrical impulses.

Analysis of pregnancy-associated plasma protein A production in human adult cardiac progenitor cells.

IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs.

Isolation and expansion of adult cardiac stem/progenitor cells in the form of cardiospheres from human cardiac biopsies and murine hearts.

The successful isolation and ex vivo expansion of resident cardiac stem/progenitor cells from human heart biopsies has allowed us to study their biological characteristics and their applications in therapeutic approaches for the repair of ischemic/infarcted heart, the preparation of tissue-engineered cardiac grafts and, possibly, the design of cellular kits for drug screening applications. From the first publication of the original method in 2004, several adjustments and slight changes have been introduced to optimize and adjust the procedure to the evolving experimental and translational needs. Moreover, due to the wide applicability of such a method (which is based on the exploitation of intrinsic functional properties of cells with regenerative properties that are present in most tissues), the key steps of this procedure have been used to derive several kinds of tissue-specific adult stem cells for preclinical or clinical purposes.

Intramyocardial injection of platelet gel promotes endogenous repair and augments cardiac function in rats with myocardial infarction.

Objectives: This study sought to explore the therapeutic potential of platelet gel for the treatment of myocardial infarction.

Background: Cardiac dysfunction after acute myocardial infarction is a major cause of heart failure. Current therapy relies on prompt reperfusion and blockage of secondary maladaptive pathways by small molecules.

Human cardiosphere-seeded gelatin and collagen scaffolds as cardiogenic engineered bioconstructs.

Cardiac tissue engineering (CTE) aims at regenerating damaged myocardium by combining cells to a biocompatible and/or bioactive matrix. Collagen and gelatin are among the most suitable materials used today for CTE approaches. In this study we compared the structural and biological features of collagen (C-RGD) or gelatin (G-FOAM)-based bioconstructs, seeded with human adult cardiac progenitor cells in the form of cardiospheres (CSps).

Cardiac cell therapy: the next (re)generation.

Heart failure remains one of the main causes of morbidity and mortality in the Western world. Current therapies for myocardial infarction are mostly aimed at blocking the progression of the disease, preventing detrimental cardiac remodeling and potentiating the function of the surviving tissue. In the last decade, great interest has arisen from the possibility to regenerate lost tissue by using cells as a therapeutic tool.

Cardiospheres and tissue engineering for myocardial regeneration: potential for clinical application.

Tissue engineering is an increasingly expanding area of research in the cardiovascular field that involves engineering, chemistry, biology and medicine. Cardiac tissue engineering (CTE) aims to regenerate myocardial damage by combining cells, matrix, biological active molecules and physiological stimuli. The rationale behind CTE applications is that in order to regenerate the ventricular wall after a myocardial infarction it is necessary to combine procedures that regenerate both cardiomyocytes and the extracellular matrix.

Differentiation of human adult cardiac stem cells exposed to extremely low-frequency electromagnetic fields.

Aims: Modulation of cardiac stem cell (CSC) differentiation with minimal manipulation is one of the main goals of clinical applicability of cell therapy for heart failure. CSCs, obtained from human myocardial bioptic specimens and grown as cardiospheres (CSps) and cardiosphere-derived cells (CDCs), can engraft and partially regenerate the infarcted myocardium, as previously described. In this paper we assessed the hypothesis that exposure of CSps and CDCs to extremely low-frequency electromagnetic fields (ELF-EMFs), tuned at Ca2+ ion cyclotron energy resonance (Ca2+-ICR), may drive their differentiation towards a cardiac-specific phenotype.