Susan Janssens | Multigene Enhancement of MSC-extracellular vesicles for Neurosenescence | Aging2026

Susan Janssens, University of Aberdeen, Scotland Title: Multigene Enhancement of MSC-extracellular vesicles for Neurosenescence Abstract: Mesenchymal stem cells (MSCs) are attractive candidates for regenerative medicine and targeted gene therapy, but stable, efficient multi-gene engineering remains a key barrier to clinical translation. Here, we evaluated a non-viral strategy combining ScreenFectA+, a cationic lipid nanoparticle, with the PiggyBac transposon system for triple-gene delivery of hTERT, PGC1α, and PGC1β into human MSCs. Transfections were performed using optimised ScreenFectA+: plasmid DNA ratios in protein-depleted medium and evaluated by qPCR, Western blotting, and Mitotracker-based assays of mitochondrial biogenesis. The optimised conditions yielded robust upregulation of all three transgenes at the mRNA level, with PGC1β protein-level increases that were detectable in puromycin-selected stem cells, showing both promoter- and gene-specific dependencies. Extracellular vesicles (EVs) derived from engineered MSCs were applied to DNA damage–induced neural progenitor cells and the HMC3 microglial cell line, and senescent markers were analysed. Together, these data provide proof-of-principle that the ScreenFectA+:PiggyBac platform can support multigene engineering across human MSC types while underscoring the need for further optimisation to achieve consistent protein expression, durable EV reprogramming, and therapeutic efficacy in Neuroenescent models. #geriatrics #agingresearch #aging #agingresearch #aging #Aging2026 #agingconference #agingmeetings #geriatrics #geriatricsconference #geriatricsmeeting #Innovinc #innovincconferences #Aging2026inPrague #ARC2026 #AgingResearch #Rejuvenation #Longevity #HealthyAging #RegenerativeMedicine #StemCells #CellularSenescence #AntiAging #Geroscience #Biotechnology #MedicalConference #LifeSciences #Prague