Therapeutic Potential of Nucleic Acids when Combined with Extracellular Vesicles.

Extracellular vesicles (EVs), endogenous nanocarriers of proteins, lipids, and genetic material, have been harnessed as intrinsic delivery vectors for nucleic acid therapies. EVs are nanosized lipid bilayer bound vesicles released from most cell types responsible for delivery of functional biologic material to mediate intercellular communication and to modulate recipient cell phenotypes. Due to their innate biological role and composition, EVs possess several advantages as delivery vectors for nucleic acid based therapies including low immunogenicity and toxicity, high bioavailability, and ability to be engineered to enhance targeting to specific recipient cells .

Magnetic Resonance Imaging and Gait Analysis Indicate Similar Outcomes Between Yucatan and Landrace Porcine Ischemic Stroke Models.

The Stroke Therapy Academic Industry Roundtable (STAIR) has recommended that novel therapeutics be tested in a large animal model with similar anatomy and physiology to humans. The pig is an attractive model due to similarities in brain size, organization, and composition relative to humans. However, multiple pig breeds have been used to study ischemic stroke with potentially differing cerebral anatomy, architecture and, consequently, ischemic stroke pathologies.

Semi-Automated Cell and Tissue Analyses Reveal Regionally Specific Morphological Alterations of Immune and Neural Cells in a Porcine Middle Cerebral Artery Occlusion Model of Stroke.

Histopathological analysis of cellular changes in the stroked brain provides critical information pertaining to inflammation, cell death, glial scarring, and other dynamic injury and recovery responses. However, commonly used manual approaches are hindered by limitations in speed, accuracy, bias, and the breadth of morphological information that can be obtained. Here, a semi-automated high-content imaging (HCI) and CellProfiler histological analysis method was developed and used in a Yucatan miniature pig permanent middle cerebral artery occlusion (pMCAO) model of ischemic stroke to overcome these limitations.

An integrative multivariate approach for predicting functional recovery using magnetic resonance imaging parameters in a translational pig ischemic stroke model.

Magnetic resonance imaging (MRI) is a clinically relevant, real-time imaging modality that is frequently utilized to assess stroke type and severity. However, specific MRI biomarkers that can be used to predict long-term functional recovery are still a critical need. Consequently, the present study sought to examine the prognostic value of commonly utilized MRI parameters to predict functional outcomes in a porcine model of ischemic stroke.

Kinetics and Specificity of HEK293T Extracellular Vesicle Uptake using Imaging Flow Cytometry.

Extracellular vesicles (EVs) are nanosized lipid bilayer-bound vesicles that are naturally secreted from most cell types as a communication mechanism to deliver proteins, lipids, and genetic material. Despite the therapeutic potential of EVs, there is limited information on EV uptake kinetics and specificity. Here, we optimized an imaging flow cytometry (IFC)-based platform to quantitatively assess dose, time, and recipient cell specificity effects on human embryonic kidney cell (HEK293T) EV internalization in a high-throughput manner.

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model.

Magnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model.

Human Neural Stem Cell Extracellular Vesicles Improve Recovery in a Porcine Model of Ischemic Stroke.

Background And Purpose: Recent work from our group suggests that human neural stem cell-derived extracellular vesicle (NSC EV) treatment improves both tissue and sensorimotor function in a preclinical thromboembolic mouse model of stroke. In this study, NSC EVs were evaluated in a pig ischemic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model.

Methods: Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS treatment was administered intravenously at 2, 14, and 24 hours post-MCAO.