Browsing by Author "Gallego-Perez, Daniel"

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    Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke
    (American Association for the Advancement of Science, 2021-03-19) Lemmerman, Luke R.; Balch, Maria H.H.; Moore, Jordan T.; Alzate-Correa, Diego; Rincon-Benavides, Maria A.; Salazar-Puerta, Ana; Gnyawali, Surya; Harris, Hallie N.; Lawrence, William; Ortega-Pineda, Lilibeth; Wilch, Lauren; Risser, Ian B.; Maxwell, Aidan J.; Duarte-Sanmiguel, Silvia; Dodd, Daniel; Guio-Vega, Gina P.; McTigue, Dana M.; Arnold, W. David; Nimjee, Shahid M.; Sen, Chandan K.; Khanna, Savita; Rink, Cameron; Higuita-Castro, Natalia; Gallego-Perez, Daniel; Surgery, School of Medicine
    Ischemic 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.
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    Neurogenic Tissue Nanotransfection in the Management of Cutaneous Diabetic Polyneuropathy
    (Elsevier, 2020-08) Roy, Sashwati; Sen, Chandan K.; Ghatak, Subhadip; Higuita-Castro, Natalia; Palakurti, Ravichand; Nalluri, Nagajyothi; Clark, Andrew; Stewart, Richard; Gallego-Perez, Daniel; Prater, Daniel N.; Khanna, Savita; Surgery, School of Medicine
    This work rests on our recent report on the successful use of tissue nanotransfection (TNT) delivery of Ascl1, Brn2, and Myt1l (TNTABM) to directly convert skin fibroblasts into electrophysiologically active induced neuronal cells (iN) in vivo. Here we report that in addition to successful neurogenic conversion of cells, TNTABM caused neurotrophic enrichment of the skin stroma. Thus, we asked whether such neurotrophic milieu of the skin can be leveraged to rescue pre-existing nerve fibers under chronic diabetic conditions. Topical cutaneous TNTABM caused elevation of endogenous NGF and other co-regulated neurotrophic factors such as Nt3. TNTABM spared loss of cutaneous PGP9.5+ mature nerve fibers in db/db diabetic mice. This is the first study demonstrating that under conditions of in vivo reprogramming, changes in the tissue microenvironment can be leveraged for therapeutic purposes such as the rescue of pre-existing nerve fibers from its predictable path of loss under conditions of diabetes.