Microfluidic processing of stem cells for autologous cell replacement

Abstract

Autologous photoreceptor cell replacement is one of the most promising approaches currently under development for the treatment of inherited retinal degenerative blindness. Unlike endogenous stem cell populations, induced pluripotent stem cells (iPSCs) can be differentiated into both rod and cone photoreceptors in high numbers, making them ideal for this application. That said, in addition to photoreceptor cells,

Outer Retinal Cell Replacement: Putting the Pieces Together

“…Clinical hPSC-derived cell therapies must be sterile and free from infectious agents, impurities, residual pluripotent cells, unidentified cell types, and genomic instabilities. 28 Such criteria must be met under strict Good Manufacturing Practice (GMP)-compliant conditions 28 , 164 – 166 and also be scalable far beyond the capacity of an average laboratory setting to be feasible for clinical trials and commercialization. Although detailed discussions of stem cell source (ES or iPS) and culture technique are beyond the scope of this review, proper induction and/or maintenance of PSCs is fundamental to any successful retinal differentiation program.…”

“…Current methods for generating hPSC retinal organoids are both time and labor-intensive, limiting their utility in clinical production pipelines. The use of bioreactors, 172 microfluidics, 166 , 173 and automated culture systems 27 are all promising approaches currently under investigation for scaling clinical-grade organoid-based technologies.…”

Adhesion-based high-throughput label-free cell sorting using ridged microfluidic channels

“…Another major drawback of these methods is the changes they induce by labeling tags or tag removal, such as the risk of tag-induced activation of sorted cells, which restrains their downstream use. 5,6 To solve this issue, negative selection of target cells can be used. Yet, even this can contaminate therapy products with magnetic beads coated with foreign antibodies.…”