Cell Reprogramming for Regeneration and Repair of the Nervous System

Clark, Isaac; Roman, Alex; Fellows, Emily; Radha, Swathi; Var, Susanna R.; Roushdy, Zachary; Borer, Samuel M.; Johnson, Samantha; Chen, Olivia; Borgida, Jacob S.; Steevens, Aleta R.; Shetty, Anala; Strell, Phoebe; Low, Walter C.; Grande, Andrew W.

doi:10.3390/biomedicines10102598

Cited by 8 publications

(4 citation statements)

References 157 publications

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“…19,20 The in vitro and in vivo generation of neurons via reprogramming of pluripotent stem cells has been demonstrated to be a rapid and efficient approach in terms of neuronal-related gene expression, morphology, connectivity, and electrophysiological properties. 21,22 In most of previously published in vitro reprogramming protocols, addition of glial cells to the culture was needed to obtain mature functional neurons. 19,23 However, in the absence of glia, Goparaju and collaborators found that transfection of human pluripotent stem cells with five mRNAs (encoding NGN1, NGN2, NGN3, ND1 and ND2) gives rise to neurons at day 7 of differentiation but only 50% of them showed 1 action potential 24 In contrast, already after 7 days and without the presence of glial cells, our protocol generates neurons with capacity to fire multiple (65% of the total) or at least one action potential (35%), making our protocol faster than the ones described to date.…”

Section: Discussionmentioning

confidence: 99%

Human cortical neurons rapidly generated by direct ES cell programming integrate into stroke-injured rat cortex

Martinez-Curiel,

Hayj,

Tsupykov

et al. 2024

Preprint

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Stroke is a major cause of long-term disability in adult humans, the neuronal loss leading to motor, sensory, and cognitive impairments. Replacement of dead neurons by intracerebral transplantation of stem cell-derived neurons for reconstruction of injured neuronal networks has potential to become a novel therapeutic strategy to promote functional recovery after stroke. Here we describe a rapid and efficient protocol for the generation of cortical neurons via direct programming of human embryonic stem (hES) cells. Our results show that 7 days overexpression of the transcription factor neurogenin 2 (NGN2) in vitro was enough to generate hES-induced cells with cortical phenotype, as revealed by immunocytochemistry and RT-qPCR, and electrophysiological properties of neurons in an intermediate stage of maturity. At 3 months after translantation into the stroke-injured rat cortex, the hES-induced neurons (hES-iNs) showed immunocytochemical markers of mature layer-specific cortical neurons and sent widespread axonal projections to several areas in both hemispheres of the host brain. Their axons became myelinated and formed synaptic contacts with host neurons, as shown by immunoelectron microscopy. Our findings demonstrate for the first time that direct transcription factor programming of hES cells can efficiently and rapidly produce cortical neurons with capacity to integrate into the stroke-injured brain.

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Section: Discussionmentioning

confidence: 99%

Human cortical neurons rapidly generated by direct ES cell programming integrate into stroke-injured rat cortex

Martinez-Curiel,

Hayj,

Tsupykov

et al. 2024

Preprint

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“…Three approaches have arisen: recruitment of neural stem cell (NSC) niches to produce neurons, reprogramming of local glial cells into neurons, and transplantation of foetal progenitor cells. Various degrees of success have emerged from studies of cellular reprogramming in animal models of neurodegenerative diseases, recently extensively reviewed elsewhere [ 226 ]. Research in this field is emerging, and potentially contributing with new ways to restore CNS function and increase health span.…”

Section: Impact Of Rejuvenating Strategies In Brain Functionmentioning

confidence: 99%

Ageing in the brain: mechanisms and rejuvenating strategies

Gaspar-Silva

Trigo

Magalhaes

2023

Cell. Mol. Life Sci.

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Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism’s fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. With the rise in life expectancy, characterizing the brain ageing process becomes fundamental for developing therapeutic interventions against the increased incidence of age-related neurodegenerative diseases and to aim for an increase in human life span and, more importantly, health span. In this review, we start by introducing the molecular/cellular hallmarks associated with brain ageing and their impact on brain cell populations. Subsequently, we assess emerging evidence on how systemic ageing translates into brain ageing. Finally, we revisit the mainstream and the novel rejuvenating strategies, discussing the most successful ones in delaying brain ageing and related diseases.

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“…Site-specific recombinase DNA enzyme called Cre, identifies the locations of 3 pairs of genes called loxp. The Cre enzyme mediates recombination, resulting in knocking out of the target genes between loxP sites (30,31).…”

Section: Cre-lox Systemmentioning

confidence: 99%

Advantages and Challenges of CRISPR-Cas9 Applications in Animal Modeling: A Concise Review CRISPR-Cas9 Applications in Animal Modeling

Abdolmajid,

Ensieh,

Ghasem

et al. 2023

JABS

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CRISPR is an extraordinarily powerful technique regulating any target gene across the genome with promising therapy intentions. CRISPR-Cas9 is a convenient tool for gene manipulation. Notwithstanding this, the broad consequence of human gene editing, particularly germinal genes, cannot be predicted. Firstly, once edited, the genes would be part of the human population for successive generations and may be impossible to remove from humanity; secondly, success is not guaranteed; thirdly, the fidelity of editing, as it could affect unrelated genes or unspecified segments of DNA; and last but not least, its influence on gene interaction, network, and signaling pathways could be difficult to be predicted. CRISPR-Cas9 mostly includes precise genome editing, rapidity and cost-effectiveness, creation of disease models, study of gene function, applications in gene therapy and translation research and wide diversity for species. The technique also ignited the moral and ethical concerns of scientific community. Ethics and safety approval for gene modification in human cells is required by the National Institutes of Health (NIH). The NIH does not currently fund studies of CRISPR in human embryos and opposes the CRISPR utilization in germline cells because these alterations would be permanent and heritable. The technology has promised with the most profound implications for cancer therapy. Recent advances in CRISPR-based technology is redefining how cancer is studied and potentially improves anti-cancer therapies. One way to improve the technology is to use machine-learning approaches to comprehending CRISPR errors and predicting more specific edits and repairing outcomes.

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Cell Reprogramming for Regeneration and Repair of the Nervous System

Cited by 8 publications

References 157 publications

Human cortical neurons rapidly generated by direct ES cell programming integrate into stroke-injured rat cortex

Human cortical neurons rapidly generated by direct ES cell programming integrate into stroke-injured rat cortex

Ageing in the brain: mechanisms and rejuvenating strategies

Advantages and Challenges of CRISPR-Cas9 Applications in Animal Modeling: A Concise Review CRISPR-Cas9 Applications in Animal Modeling

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