Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies

Diaz-Starokozheva, Ludmila; Das, Devleena; Gu, Xiangming; Moore, Jordan; Lemmerman, Luke R.; Valerio, Ian L.; Powell, Heather M.; Higuita‐Castro, Natalia; Go, Michael R.; Palmer, Andre F.; Gallego‐Perez, Daniel

doi:10.1007/s12195-020-00621-4

Cited by 10 publications

(9 citation statements)

References 78 publications

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“…A TNT-based topical CRISPR/dCas9 strategy was used to develop chimeric versions of dCas9 fused with TET to achieve TP53 demethylation.TP53 demethylation improved wound closure. This proves that TNT can be employed to improve topical wound closure [6].…”

Section: Discussionmentioning

confidence: 65%

“…TNT was used to deliver reprogramming factors to the skin in 2 injury-induced ischemia mouse models, which resulted in the formation of vascular networks that successfully anastomosed with the systemic circulation, recovered tissue, and managed to rescue the entire limb of mice, implying that TNT could be used to rescue necrotizing tissue [11]. TNT could also be employed to develop tissue early intervention measures to deal with severe tissue ischemia since ischemic tissue can be saved using polymerized hemoglobin (PolyHb)-based oxygen Nanocarriers and Tissue Nano-Transfection (TNT) [6].…”

Section: Discussionmentioning

confidence: 99%

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Applications of Tissue Nano-Transfection Technology (TNT): A Systematic Review

2023

IJADR

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Aim: The purpose of this systematic review was to provide an overview of recent advances in applications of Tissue Nano-transfection and to assess its applicability in the treatment of various diseases. Materials and Methods: A systematic literature search was conducted in 2 electronic databases (PubMed and Science direct). The research findings were incorporated from inception. Initial screening was performed to select articles for review based on title and abstract. The full texts of selected articles were then evaluated, and relevant articles were chosen to be included in this review. Results: 29 articles were identified during the literature search. There are 16 From Science Direct and 13 in PubMed. This review included 8 research articles. Conclusion: TNT advancement has made a positive impact on the future of treatment of certain diseases by providing one-touch and in-site treatments. There is a need to scale up TNT experiments on animals and humans, as well as testing this approach on a broader range of diseases. Although tissue Nano-transfection technology is still in its early stages, it has already proven to be a highly promising approach in the field of regenerative medicine.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Applications of Tissue Nano-Transfection Technology (TNT): A Systematic Review

2023

IJADR

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“…Nonviral approaches to gene/cargo delivery have the potential to facilitate the development of highly translational cell therapies for a wide variety of conditions (18,19,(41)(42)(43)(44)(45). Here, we showed that nonviral nanotransfection of Etv2, Foxc2, and Fli1 (EFF) into fibroblasts can drive reprogramming-based vasculogenic cell therapies of relevance to ischemic stroke when deployed intracranially.…”

Section: Discussionmentioning

confidence: 99%

Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke

et al. 2021

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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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“…Moreover, the induction of Tuj1 immunoreactivity in fibroblast cultures (Figure 3B-D) suggests that ABM-loaded EVs could potentially be used to drive proneuronal responses/conversions in non-neuronal cells, which could be of relevance to efforts focused on the development of reprogramming-based cellular therapies for a wide variety of neurological conditions/disorders. [13,37,48,49]…”

Section: Designer Evs Can Transfer Plasmid Dna To Recipient Cells And...mentioning

confidence: 99%

Designer Extracellular Vesicles Modulate Pro‐Neuronal Cell Responses and Improve Intracranial Retention

Ortega‐Pineda

Sunyecz

Salazar-Puerta

et al. 2022

Adv Healthcare Materials

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Gene/oligonucleotide therapies have emerged as a promising strategy for the treatment of different neurological conditions. However, current methodologies for the delivery of neurogenic/neurotrophic cargo to brain and nerve tissue are fraught with caveats, including reliance on viral vectors, potential toxicity, and immune/inflammatory responses. Moreover, delivery to the central nervous system is further compounded by the low permeability of the blood brain barrier. Extracellular vesicles (EVs) have emerged as promising delivery vehicles for neurogenic/neurotrophic therapies, overcoming many of the limitations mentioned above. However, the manufacturing processes used for therapeutic EVs remain poorly understood. Here, we conducted a detailed study of the manufacturing process of neurogenic EVs by characterizing the nature of cargo and surface decoration, as well as the transfer dynamics across donor cells, EVs, and recipient cells. Neurogenic EVs loaded with Ascl1, Brn2, and Myt1l (ABM) are found to show enhanced neuron-specific tropism, modulate electrophysiological activity in neuronal cultures, and drive pro-neurogenic conversions/reprogramming. Moreover, murine studies demonstrate that surface decoration with glutamate receptors appears to mediate enhanced EV delivery to the brain. Altogether, the results indicate that ABM-loaded designer EVs can be a promising platform nanotechnology to drive pro-neuronal responses, and that surface functionalization with glutamate receptors can facilitate the deployment of EVs to the brain.

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Early Intervention in Ischemic Tissue with Oxygen Nanocarriers Enables Successful Implementation of Restorative Cell Therapies

Cited by 10 publications

References 78 publications

Applications of Tissue Nano-Transfection Technology (TNT): A Systematic Review

Applications of Tissue Nano-Transfection Technology (TNT): A Systematic Review

Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke

Designer Extracellular Vesicles Modulate Pro‐Neuronal Cell Responses and Improve Intracranial Retention

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