Lemmerman, Luke R.Balch, Maria H.H.Moore, Jordan T.Alzate-Correa, DiegoRincon-Benavides, Maria A.Salazar-Puerta, AnaGnyawali, SuryaHarris, Hallie N.Lawrence, WilliamOrtega-Pineda, LilibethWilch, LaurenRisser, Ian B.Maxwell, Aidan J.Duarte-Sanmiguel, SilviaDodd, DanielGuio-Vega, Gina P.McTigue, Dana M.Arnold, W. DavidNimjee, Shahid M.Sen, Chandan K.Khanna, SavitaRink, CameronHiguita-Castro, NataliaGallego-Perez, Daniel2022-06-232022-06-232021-03-19Lemmerman LR, Balch MHH, Moore JT, et al. Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke. Sci Adv. 2021;7(12):eabd4735. Published 2021 Mar 19. doi:10.1126/sciadv.abd4735https://hdl.handle.net/1805/29403Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here, we used fibroblasts nanotransfected with Etv2, Foxc2, and Fli1 (EFF) to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days after injection. MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Together, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., nonviral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke.en-USAttribution-NonCommercial 4.0 InternationalCell differentiationCellular reprogrammingFibroblastsIschemic strokeArticle