Extracellular vesicle biogenesis of three-dimensional human pluripotent stem cells in a novel Vertical-Wheel bioreactor.

Extracellular vesicles (EVs) secreted by human-induced pluripotent stem cells (hiPSCs) have great potential as cell-free therapies in various diseases, including prevention of blood-brain barrier senescence and stroke. However, there are still challenges in pre-clinical and clinical use of hiPSC-EVs due to the need for large-scale production of a large quantity. Vertical-Wheel bioreactors (VWBRs) have design features that allow the biomanufacturing of hiPSC-EVs using a scalable aggregate or microcarrier-based culture system under low shear stress.

Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived from Human Pluripotent Stem Cells.

The choroid plexus (ChP) is a complex structure in the human brain that is responsible for the secretion of cerebrospinal fluid (CSF) and forming the blood-CSF barrier (B-CSF-B). Human-induced pluripotent stem cells (hiPSCs) have shown promising results in the formation of brain organoids in vitro; however, very few studies to date have generated ChP organoids. In particular, no study has assessed the inflammatory response and the extracellular vesicle (EV) biogenesis of hiPSC-derived ChP organoids.

Upscaling human mesenchymal stromal cell production in a novel vertical-wheel bioreactor enhances extracellular vesicle secretion and cargo profile.

Human mesenchymal stromal cells (hMSCs) are mechanically sensitive undergoing phenotypic alterations when subjected to shear stress, cell aggregation, and substrate changes encountered in 3D dynamic bioreactor cultures. However, little is known about how bioreactor microenvironment affects the secretion and cargo profiles of hMSC-derived extracellular vesicles (EVs) including the subset, "exosomes", which contain therapeutic proteins, nucleic acids, and lipids from the parent cells. In this study, bone marrow-derived hMSCs were expanded on 3D Synthemax II microcarriers in the PBS mini 0.

Human Forebrain Organoid-Derived Extracellular Vesicle Labeling with Iron Oxides for In Vitro Magnetic Resonance Imaging.

The significant roles of extracellular vesicles (EVs) as intracellular mediators, disease biomarkers, and therapeutic agents, make them a scientific hotspot. In particular, EVs secreted by human stem cells show significance in treating neurological disorders, such as Alzheimer’s disease and ischemic stroke. However, the clinical applications of EVs are limited due to their poor targeting capabilities and low therapeutic efficacies after intravenous administration.

Bioengineering Human Pluripotent Stem Cell-Derived Retinal Organoids and Optic Vesicle-Containing Brain Organoids for Ocular Diseases.

Retinal organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that mimic the retina's spatial and temporal differentiation, making them useful as in vitro retinal development models. Retinal organoids can be assembled with brain organoids, the 3D self-assembled aggregates derived from hPSCs containing different cell types and cytoarchitectures that resemble the human embryonic brain. Recent studies have shown the development of optic cups in brain organoids.

Dynamic 3D On-Chip BBB Model Design, Development, and Applications in Neurological Diseases.

The blood-brain barrier (BBB) is a vital structure for maintaining homeostasis between the blood and the brain in the central nervous system (CNS). Biomolecule exchange, ion balance, nutrition delivery, and toxic molecule prevention rely on the normal function of the BBB. The dysfunction and the dysregulation of the BBB leads to the progression of neurological disorders and neurodegeneration.