Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications

Venkatesh, Kumar; Ghosh, Shounak K.; Mullick, Madhubanti; Manivasagam, Geetha; Sen, Dwaipayan

doi:10.1007/s00441-019-03039-1

Cited by 157 publications

(146 citation statements)

References 245 publications

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“…Mobile impairment occurs in millions of aging and mature adults, worldwide, as a result of neuromuscular and neurodegenerative disease (Cowling & Thielemans, ; Pipis, Rossor, Laura, & Reilly, ) as well as chronic and traumatic injury to the brain and/or spinal cord (Alizadeh, Dyck, & Karimi‐Abdolrezaee, ; New & Biering‐Sorensen, ). Traditional therapies have sought to restore mobility through direct action on neuronal cells (Silva, Sousa, Reis, & Salgado, ; Venkatesh, Ghosh, Mullick, Manivasagam, & Sen, ), but have reported modest recovery with considerable disparity in mobility outcomes (Filipp et al, ; Gupta, Jaiswal, Norman, & Depaul, ). Mounting evidence suggests that both motor deficit and recovery in adults depend largely upon the plasticity of the neuromuscular junction (NMJ), a biochemical synapse that transduces electrical impulses from the brain into voluntary contraction of striated muscle (Burns et al, ; Khorasanizadeh et al, ; Lepore, Casola, Dobrowolny, & Musaro, ).…”

Section: Introductionmentioning

confidence: 99%

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Singh

Robles

Vázquez

2020

J Tissue Eng Regen Med

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Neurodegeneration and dysfunction cause mobility impairment and/or paralysis in millions of adults, worldwide. Motor deficit and recovery in adults depend upon the plasticity of the neuromuscular junction (NMJ), a tripartite, biochemical synapse that transduces electrical impulses from the brain into voluntary contraction of skeletal muscle. Nonmyelinating Schwann cells (nmSCs) of the NMJ have been increasingly recognized as active synaptic partners with motor neurons and muscle and have become recent therapeutic targets for regeneration. nmSC synaptic transmission, plasticity, and growth are strongly modulated by brain-derived neurotrophic factor (BDNF), whose regenerative abilities have been explored through emerging biomaterials and tissue-engineered systems, as well as via clinical trials. Experimental models engineered to investigate integrated NMJ response(s) to local gradients of BDNF will both advance our understanding of key modulators of synaptic activity, postinjury, and aid in the development of NMJ-targeted, regenerative therapies to restore mobility. The current study examined the ability of nmSCs to respond to microfluidically controlled BDNF signaling upon different haptotactic substrates of motor neurons (MNs) and laminin adhesion coating. Tests seeding nmSCs sequentially with MNs illustrated that sequential seeding reported a fivefold increase in levels of tropomyosin receptor kinase B expression in response to BDNF signaling and a nearly fivefold increase in migration distance along BDNF gradients. By contrast, concurrent seeding of MNs and nmSCs upon laminin adhesion coating illustrated a difference in migration distance of less than one third-fold over control. Our findings are among the first to examine migratory responses of nmSCs for regenerative strategies and highlight the potential to restabilize NMJ synaptic activity by affecting nmSC behaviors through therapeutic BDNF and seeding with MNs.

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Section: Introductionmentioning

confidence: 99%

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Singh

Robles

Vázquez

2020

J Tissue Eng Regen Med

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“…Currently, the stem cell‐based transplantation therapy has been purported to replace lost neurons and glial cells after SCI at the injury site (Carelli et al, 2014; Venkatesh et al, 2019). However, stem cell‐based transplantation is mainly limited by the low survival rate of the grafted stem cells and tumor formation risk due to its multiple differentiation potential (Shi et al, 2016; de Luca et al, 2015; Kolar et al, 2014).…”

Section: Chitosan Scaffold Protects Grafted Stem Cells In Vitro and Imentioning

confidence: 99%

“…Currently, the stem cell-based transplantation therapy has been purported to replace lost neurons and glial cells after SCI at the injury site (Carelli et al, 2014;Venkatesh et al, 2019). However, stem cellbased transplantation is mainly limited by the low survival rate of the grafted stem cells and tumor formation risk due to its multiple differentiation potential (Shi et al, 2016;de Luca et al, 2015;Kolar et al, 2014).The combinations of a variety of stem cells and biomaterial scaffold therapies may be necessary for addressing the problems faced in the course of stem cell-based transplantation treatment of the SCI, wherein scaffolds based stem cells present better engraftment and neural differentiation potential than the intralesional injection transplantation group (Ji et al, 2016;Kim and Kim, 2016;Li et al, 2018a,b,d).…”

Section: Chitosan Scaffold Protects Grafted Stem Cells In Vitro and Imentioning

confidence: 99%

Application of stem cells and chitosan in the repair of spinal cord injury

Zhou

et al. 2019

Intl J of Devlp Neuroscience

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Cytology and histology obstacles have been the main barriers to multiple tissues injury repair. In search of the most promising treatment strategies for spinal cord injury (SCI), stem cell‐based transplantation coupled with various materials/technologies have been explored extensively to enhance SCI repair. Chitosan (CS) has demonstrated immense potential for widespread application in the form of scaffolds and micro‐particles for SCI repair. The current review summarizes the evidences for stem cell‐based transplantation and CS in SCI repair. Stem cells transplantation, which plays a key role in the repair of SCI, mainly results from its neural differentiation potential and neurotrophic effects. Application of CS enhances the survival of grafted stem cells, upregulates the expression level of neurotrophic factors and heightens the neural differentiation of stem cells as well as the functional recovery of spinal cord. Meanwhile, CS can also be exploited as growth factors/RNA carriers to control the release of regenerating molecules which are beneficial to damage spinal cord repair.

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“…The heterogeneous, complex, and time‐sensitive pathophysiology of SCI has hampered the identification of the proper set of therapeutic targets for tissue repair. Nevertheless, numerous single or in combination strategies have been investigated to improve functional recovery after SCI (Badhiwala et al, ; Venkatesh, Ghosh, Mullick, Manivasagam, & Sen, ). In this context, cell therapy is particularly well suited to address the multi‐factorial nature of secondary events following SCI, offering a neuroprotective and neuroregenerative competence, which confers a compelling widely investigated clinical potential (Assinck, Duncan, Hilton, Plemel, & Tetzlaff, ; Badner, Siddiqui, & Fehlings, ; Jin, Medress, Azad, Doulames, & Veeravagu, ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

Maqueda

Rodríguez

2019

J Tissue Eng Regen Med

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Spinal cord injury (SCI) is a devastating event with huge personal and social costs, for which there is no effective treatment. Cell therapy constitutes a promising therapeutic approach for SCI; however, its clinical potential is seriously limited by their low survival in the hostile conditions encompassing the acute phase of SCI. Human HC016 (hHC016) cells, generated from expanded human adipose mesenchymal stem cells (hAMSCs) and pulsed with a patented protocol with hydrogen peroxide (H2O2), are expected to acquire improved resistance to oxidative environments which appears as a major limiting factor hampering the engrafting success. Our specific aim was to assess whether H2O2‐pulsed hHC016 cells had an improved survival and thus therapeutic efficacy in a rat contusion model of acute SCI when grafted 48 hr after injury. Functional recovery was evaluated up to 56 days post‐injury (dpi) by locomotor (open field test and CatWalk) and sensory (Von Frey and Hargreaves) tests. Besides, histological evaluation of transplanted cell survival and tissue protection/regeneration was also performed. Functional results showed a statistically significant improvement on locomotor recovery outcomes with hHC016 cells. Accordingly, superior cell survival in correlation with long‐term neuroprotection, higher axonal regeneration, and reduced astroglial and microglial reactivity was also observed with hHC016 cells. These results demonstrate an enhanced survival capacity of hHC016 cells resulting in improved functional and histological outcomes as compared with hAMSCs, indicating that hHC016 cell transplants may constitute a promising cell therapy for acute SCI.

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Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications

Cited by 157 publications

References 245 publications

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Application of stem cells and chitosan in the repair of spinal cord injury

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

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