Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke
| Autor: | Dana M. McTigue, Chandan K. Sen, Aidan J. Maxwell, Daniel Gallego-Perez, Jordan T. Moore, Luke R. Lemmerman, Lilibeth Ortega-Pineda, Gina P. Guio-Vega, Hallie Harris, Lauren Wilch, Diego Alzate-Correa, Savita Khanna, Maria Angelica Rincon-Benavides, Ian B. Risser, Daniel J. Dodd, Maria H.H. Balch, W. David Arnold, Shahid M Nimjee, Ana Salazar-Puerta, Silvia Duarte-Sanmiguel, Surya Gnyawali, Cameron Rink, William Lawrence, Natalia Higuita-Castro |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell
Glial scar 03 medical and health sciences Mice 0302 clinical medicine Vasculogenesis Vascularity Medicine Animals Health and Medicine Research Articles 030304 developmental biology Progenitor Ischemic Stroke 0303 health sciences Multidisciplinary business.industry SciAdv r-articles Cell Differentiation Fibroblasts Cellular Reprogramming Disease Models Animal medicine.anatomical_structure Applied Sciences and Engineering FLI1 Cancer research medicine.symptom business Perfusion Reprogramming 030217 neurology & neurosurgery Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Fibroblasts nonvirally programmed to convert into induced endothelial cells show therapeutic potential for ischemic stroke. 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. |
| Databáze: | OpenAIRE |
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