The Utility of Miniaturized Adsorbers in Exploring the Cellular and Molecular Effects of Blood Purification: A Pilot Study with a Focus on Immunoadsorption in Multiple Sclerosis.
Andreas KörtgeAnne BreitrückSandra DoßJacqueline HofrichterSophie-Charlotte NelzHorst KrüsemannReinhold WasserkortBrit FitznerMichael HeckerSteffen MitznerUwe Klaus ZettlPublished in: International journal of molecular sciences (2024)
Immunoadsorption (IA) has proven to be clinically effective in the treatment of steroid-refractory multiple sclerosis (MS) relapses, but its mechanism of action remains unclear. We used miniaturized adsorber devices with a tryptophan-immobilized polyvinyl alcohol (PVA) gel sorbent to mimic the IA treatment of patients with MS in vitro. The plasma was screened before and after adsorption with regard to disease-specific mediators, and the effect of the IA treatment on the migration of neutrophils and the integrity of the endothelial cell barrier was tested in cell-based models. The in vitro IA treatment with miniaturized adsorbers resulted in reduced plasma levels of cytokines and chemokines. We also found a reduced migration of neutrophils towards patient plasma treated with the adsorbers. Furthermore, the IA-treated plasma had a positive effect on the endothelial cell barrier's integrity in the cell culture model. Our findings suggest that IA results in a reduced infiltration of cells into the central nervous system by reducing leukocyte transmigration and preventing blood-brain barrier breakdown. This novel approach of performing in vitro blood purification therapies on actual patient samples with miniaturized adsorbers and testing their effects in cell-based assays that investigate specific hypotheses of the pathophysiology provides a promising platform for elucidating the mechanisms of action of those therapies in various diseases.
Keyphrases
- multiple sclerosis
- blood brain barrier
- endothelial cells
- stem cells
- single cell
- case report
- cell death
- cell therapy
- high resolution
- combination therapy
- single molecule
- mesenchymal stem cells
- brain injury
- subarachnoid hemorrhage
- smoking cessation
- solid phase extraction
- cerebral ischemia
- cell cycle arrest
- capillary electrophoresis
- liquid chromatography
- metal organic framework