Big bottlenecks in cardiovascular tissue engineering.

Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges

Exocytosis of nanoparticles from cells: Role in cellular retention and toxicity

Over the past decade, nanoparticles (NPs) have been increasingly developed in various biomedical applications such as cell tracking, biosensing, contrast imaging, targeted drug delivery, and tissue engineering. Their versatility in design and function has made them an attractive, alternative choice in many biological and biomedical applications. Cellular responses to NPs, their uptake, and adverse biological effects caused by NPs are rapidly-growing research niches. However, NP excretion and its underlying mechanisms and cell signaling pathways are yet elusive. In this review, we present an overview of how NPs are handled intracellularly and how they are excreted from cells following the uptake. We also discuss how exocytosis of nanomaterials impacts both the therapeutic delivery of nanoscale objects and their nanotoxicology

Nanoparticles-induced inflammatory cytokines in human plasma concentration manner: An ignored factor at the nanobio-interface

Properties of nanoparticles (NPs) are responsible for their interaction with various biomolecules such as proteins in biological environments. Amount and composition of the proteins associated with NPs, i.e. protein corona, are strongly dependent on physicochemical characteristics of the particles, as well as incubation parameters including temperature and protein concentration. More importantly, the protein corona can define the biological fate of the NPs. Here, we demonstrate that variations in the concentration of plasma protein led to significant changes in the composition of the hard corona adsorbed on the surface of different NPs including hydrophilic amorphous silica (SiO), hydrophilic crystalline zeolite (EMT), and hydrophobic sulfonatedmodified polystyrene. Alteration in the corona composition of the NPs is a result of the plasma concentration, i.e. it affects the release of inflammatory cytokines in a plasma concentration-dependent manner. The amorphous silica nanoparticles with hydrophilic surfaces induced the release of the inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor (TNFα) in 10 % plasma concentration, but not at higher concentrations. A reverse trend was observed for the hydrophobic, sulfonated-modified polystyrene NPs. Remarkably the hydrophilic highly porous EMT NPs exhibited no cellular toxicity regardless to the plasma concentration. The results obtained in this study can be used to define optimal pathways for nanoparticles administration in vivo. These findings can assist researchers to better understand how NPs with different surface properties may interact with various proteins in vivo, and elucidate safety considerations for their biomedical applications

Epicardial FSTL1 reconstitution regenerates the adult mammalian heart

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans

Big bottlenecks in cardiovascular tissue engineering.

Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges