Stem cells and their extracellular vesicles as natural and bioinspired carriers for the treatment of neurological disorders

One of the most explored strategies to cure neurological disorders is the transplantation of stem cells and their derived products. Different stem cells, as well as their extracellular vesicles (EV), modified or not, have been administrated in a large array of preclinical neurological disorder models. EV represent the hope of a “cell-free” therapy that would combine the therapeutic potential of stem cells without their drawbacks. Stem cells and EV showed various degrees of efficiency but, overall, provided benefits and improvements. The administration route has a considerable impact on stem cell and EV safety and therapeutic effect. However, despite evidences of preclinical success, the different strategies developed based on stem cells to treat neurological disorders do not exactly recapitulate in clinical trials. Discrepancies between preclinical and clinical experimental conditions and settings, cell availability and difficulties to scale up and to produce cells and EV in a Good Manufacturing Practices (GMP) environment limit translation.     

Rapid isolation and quantification of extracellular vesicles from suspension-adapted human embryonic kidney cells using capillary-channeled polymer fiber spin-down tips

Exosomes, a subset of extracellular vesicles (EVs, 30–200-nm diameter), serve as biomolecular snapshots of their cell of origin and vehicles for intercellular communication, playing roles in biological processes, including homeostasis maintenance and immune modulation. The large-scale processing of exosomes for use as therapeutic vectors has been proposed, but these applications are limited by impure, low-yield recoveries from cell culture milieu (CCM). Current isolation methods are also limited by tedious and laborious workflows, especially toward an isolation of EVs from CCM for therapeutic applications. Employed is a rapid (<10 min) EV isolation method on a capillary-channeled polymer fiber spin-down tip format. EVs are isolated from the CCM of suspension-adapted human embryonic kidney cells (HEK293), one of the candidate cell lines for commercial EV production. This batch solid-phase extraction technique allows 10¹² EVs to be obtained from only 100-µl aliquots of milieu, processed using a benchtop centrifuge. The tip-isolated EVs were characterized using transmission electron microscopy, multi-angle light scattering, absorbance quantification, an enzyme-linked immunosorbent assay to tetraspanin marker proteins, and a protein purity assay. It is believed that the demonstrated approach has immediate relevance in research and analytical laboratories, with opportunities for production-level scale-up projected.