Ultrasound-mediated delivery of flexibility-tunable polymer drug conjugates for treating glioblastoma.

Effective chemotherapy delivery for glioblastoma multiforme (GBM) is limited by drug transport across the blood-brain barrier and poor efficacy of single agents. Polymer-drug conjugates can be used to deliver drug combinations with a ratiometric dosing. However, the behaviors and effectiveness of this system have never been well investigated in GBM models.

Extracellular vesicles enriched with an endothelial cell pro-survival microRNA affects skin tissue regeneration.

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions.

An Blood-brain Barrier Model to Study the Penetration of Nanoparticles.

The blood-brain barrier (BBB), a crucial protection mechanism in the central nervous system (CNS), is a selective barrier comprised of endothelial cells. It hampers the development of therapeutic and diagnostic tools for neurological diseases due to the poor penetration of most of these agents. Rationally engineered nanoparticles (NP) can facilitate the transport of therapeutic and diagnostic agents across the BBB.

Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo.

MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics.

BBB pathophysiology-independent delivery of siRNA in traumatic brain injury.

Small interfering RNA (siRNA)-based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB.

Analysis of Neat Biofluids Obtained During Cardiac Surgery Using Nanoparticle Tracking Analysis: Methodological Considerations.

Small extracellular vesicles (sEVs) are those nanovesicles 30-150 nm in size with a role in cell signalling and potential as biomarkers of disease. Nanoparticle tracking analysis (NTA) techniques are commonly used to measure sEV concentration in biofluids. However, this quantification technique can be susceptible to sample handing and machine settings.

miR-210 Enhances the Therapeutic Potential of Bone-Marrow-Derived Circulating Proangiogenic Cells in the Setting of Limb Ischemia.

Therapies based on circulating proangiogenic cells (PACs) have shown promise in ischemic disease models but require further optimization to reach the bedside. Ischemia-associated hypoxia robustly increases microRNA-210 (miR-210) expression in several cell types, including endothelial cells (ECs). In ECs, miR-210 represses EphrinA3 (EFNA3), inducing proangiogenic responses.

Endothelial Progenitor Cells influence acute and subacute stroke hemodynamics.

Background: Endothelial Progenitor Cells (EPCs) are a circulating stem cell population with in vivo capacity of promoting angiogenesis after ischemic events. Despite the promising preclinical data, their potential integration with reperfusion therapies and hemodynamic evolution of stroke patients is still unknown. Our aim was to determine the association of EPCs with acute, subacute and chronic hemodynamic features.

Endothelial progenitor cells enhance blood-brain barrier permeability in subacute stroke.

Objective: To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome.

Methods: We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months.

Synthetic microparticles conjugated with VEGF improve the survival of endothelial progenitor cells via microRNA-17 inhibition.

Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy.

Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential.

Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process.

Stem Cell-Based Human Blood-Brain Barrier Models for Drug Discovery and Delivery.

The development of novel neuropharmaceuticals requires the evaluation of blood-brain barrier (BBB) permeability and toxicity. Recent studies have highlighted differences in the BBB among different species, with the most important differences involving the expression of P-glycoprotein (P-gp), multidrug resistance-associated proteins, transporters, and claudins. In addition, functional studies have shown that brain pharmacokinetics of P-glycoprotein substrates are different in humans and rodents.

Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions.

Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.

A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells.

Heparin-functionalized chitosan scaffolds for bone tissue engineering.

The aim of this study is to investigate the effects of heparin-functionalized chitosan scaffolds on the activity of preosteoblasts. The chitosan scaffolds having the pore size of ∼100 μm were prepared by a freeze-drying method. Two different methods for immobilization of heparin to chitosan scaffolds were successfully performed.

Controlling the neuronal differentiation of stem cells by the intracellular delivery of retinoic acid-loaded nanoparticles.

The manipulation of endogenous stem cell populations from the subventricular zone (SVZ), a neurogenic niche, creates an opportunity to induce neurogenesis and influence brain regenerative capacities in the adult brain. Herein, we demonstrate the ability of polyelectrolyte nanoparticles to induce neurogenesis exclusively after being internalized by SVZ stem cells. The nanoparticles are not cytotoxic for concentrations equal or below 10 μg/mL.

Insulin and heparin co-immobilized 3D polyester fabrics for the cultivation of fibroblasts in low-serum media.

Insulin and/or heparin immobilized/co-immobilized non-woven polyester fabric (NWPF) discs were developed for the cultivation of L929 mouse fibroblasts in low-serum media. At first, NWPF discs were hydrolyzed to obtain a carboxylic acid group-introduced matrix (NWPF-hydrolyzed). Insulin and heparin co-immobilized NWPF (NWPF-insulin-heparin) was prepared by the grafting of PEO onto NWPF-hydrolyzed disc (NWPF-PEO), followed by the reaction first with insulin and then heparin.