Spinal motor neuron transplantation to enhance nerve reconstruction strategies: Towards a cell therapy

Bazarek, Stanley; Johnston, Benjamin R.; Sten, Margaret; Mandeville, Ross; Eggan, Kevin; Wainger, Brian J.; Brown, Justin M.

doi:10.1016/j.expneurol.2022.114054

Cited by 7 publications

(5 citation statements)

References 63 publications

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“…A recent review article focused on neuromuscular preservation for denervated muscles using spinal motor neuron (SMN) transplantation and discussed permanent treatment strategies with electrical stimulation [ 27 ]. In the article, the authors discuss not only reconstruction of motor function due to complete conus and cauda equina injury, but also reconstruction of bladder function and application of diaphragmatic pacing for ALS.…”

Section: Discussionmentioning

confidence: 99%

A Therapeutic Strategy for Lower Motor Neuron Disease and Injury Integrating Neural Stem Cell Transplantation and Functional Electrical Stimulation in a Rat Model

Tokutake

Takeuchi

Kurimoto

et al. 2022

IJMS

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Promising treatments for upper motor neuron disease are emerging in which motor function is restored by brain–computer interfaces and functional electrical stimulation. At present, such technologies and procedures are not applicable to lower motor neuron disease. We propose a novel therapeutic strategy for lower motor neuron disease and injury integrating neural stem cell transplantation with our new functional electrical stimulation control system. In a rat sciatic nerve transection model, we transplanted embryonic spinal neural stem cells into the distal stump of the peripheral nerve to reinnervate denervated muscle, and subsequently demonstrated that highly responsive limb movement similar to that of a healthy limb could be attained with a wirelessly powered two-channel neurostimulator that we developed. This unique technology, which can reinnervate and precisely move previously denervated muscles that were unresponsive to electrical stimulation, contributes to improving the condition of patients suffering from intractable diseases of paralysis and traumatic injury.

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Section: Discussionmentioning

confidence: 99%

A Therapeutic Strategy for Lower Motor Neuron Disease and Injury Integrating Neural Stem Cell Transplantation and Functional Electrical Stimulation in a Rat Model

Tokutake

Takeuchi

Kurimoto

et al. 2022

IJMS

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“…Replenishing injured or lost spinal cord motor neurons is an effective strategy for promoting neural reconstruction and may contribute to improving injured spinal cord function ( Bazarek et al, 2022 ). The forced expression of seven TFs (Ascl1, Brn2, Myt1l, Lhx3, Hb9, Isl1, and NeuroG2) transdifferentiates mouse fibroblasts into induced motor neurons (iMNs).…”

Section: Transdifferentiation Of Neuronal Subtypesmentioning

confidence: 99%

A cutting-edge strategy for spinal cord injury treatment: resident cellular transdifferentiation

Fang,

Chen,

Zheng

et al. 2023

Front. Cell. Neurosci.

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Spinal cord injury causes varying degrees of motor and sensory function loss. However, there are no effective treatments for spinal cord repair following an injury. Moreover, significant preclinical advances in bioengineering and regenerative medicine have not yet been translated into effective clinical therapies. The spinal cord’s poor regenerative capacity makes repairing damaged and lost neurons a critical treatment step. Reprogramming-based neuronal transdifferentiation has recently shown great potential in repair and plasticity, as it can convert mature somatic cells into functional neurons for spinal cord injury repair in vitro and in vivo, effectively halting the progression of spinal cord injury and promoting functional improvement. However, the mechanisms of the neuronal transdifferentiation and the induced neuronal subtypes are not yet well understood. This review analyzes the mechanisms of resident cellular transdifferentiation based on a review of the relevant recent literature, describes different molecular approaches to obtain different neuronal subtypes, discusses the current challenges and improvement methods, and provides new ideas for exploring therapeutic approaches for spinal cord injury.

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“…The pipeline of therapies designed to promote peripheral reinnervation or slow degeneration in a multitude of conditions is expanding dramatically. This is typified by the explosion in amyotrophic lateral sclerosis (ALS) trials to slow or reverse degeneration, immune therapies in inflammatory conditions, and the numerous therapeutic avenues in peripheral nerve injury including stimulation, stem cells, growth factors, and varied surgical techniques [3][4][5][6][7]. This context demands a re-evaluation of standard clinical and pre-clinical measurements of nerve health and the innovation of measures that can serve as novel biomarkers.…”

Section: Introductionmentioning

confidence: 99%

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration, and regeneration: part 1, neurophysiology

et al. 2023

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Peripheral neuroregeneration research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures that can serve as biomarkers of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, such biomarkers can elucidate regeneration mechanisms and open new avenues for research. Without these measures, clinical decision-making falls short, and research becomes more costly, time-consuming, and sometimes infeasible. As a companion to Part 2, which is focused on non-invasive imaging, Part 1 of this two-part scoping review systematically identifies and critically examines many current and emerging neurophysiological techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

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Spinal motor neuron transplantation to enhance nerve reconstruction strategies: Towards a cell therapy

Cited by 7 publications

References 63 publications

A Therapeutic Strategy for Lower Motor Neuron Disease and Injury Integrating Neural Stem Cell Transplantation and Functional Electrical Stimulation in a Rat Model

A Therapeutic Strategy for Lower Motor Neuron Disease and Injury Integrating Neural Stem Cell Transplantation and Functional Electrical Stimulation in a Rat Model

A cutting-edge strategy for spinal cord injury treatment: resident cellular transdifferentiation

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration, and regeneration: part 1, neurophysiology

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