Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback.

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Application of developmental principles for spinal cord repair after injury

The International Journal of Developmental Biology ◽

10.1387/ijdb.210110fp ◽

2021 ◽

Author(s):

Florentia Papastefanaki

Keyword(s):

Spinal Cord ◽

Stem Cell ◽

Therapeutic Interventions ◽

Stem Cell Population ◽

Cellular Mechanisms ◽

Cord Injury ◽

Function Loss ◽

Developmental Principles ◽

Spontaneous Regeneration ◽

Spinal Cord Repair

The superiority of the mammalian central nervous system (CNS) among other vertebrates does not involve an advanced capacity for regeneration and any insult results to irreversible function loss. Spinal cord injury (SCI) is one example of CNS trauma affecting thousands of individuals, mostly young, each year. Despite enormous progress in our comprehension of the molecular and cellular mechanisms underlying the pathophysiology after SCI, also providing targets for therapeutic interventions, so far, no efficient therapy exists, emphasizing the necessity for further research. A breadth of studies have demonstrated that, after SCI, principles of development come at play either to promote or to prohibit spontaneous regeneration and their accurate manipulation holds promise toward functional recovery. In this overview, some of the most recent and important studies are discussed that offer explicitly novel input from the field of development to the field of CNS repair regarding the modification of the inhibitory environment of the injured spinal cord – majorly referring to the glial scar – the activation of endogenous cell populations such as ependymal stem cells and oligodendrocyte precursor cells, and the developmental transcriptional program that is transiently activated in neurons after injury. Furthermore, current advances in stem cell technology are highlighted in terms of refinement and precise design of the appropriate stem cell population to be transplanted not only for cell replacement but also for modulation of the host environment. As single-dimension applications were not yet clinically successful, combinatorial strategies tackling more than one targets are suggested as more auspicious.

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Pentapeptide IKVAV-engineered hydrogels for neural stem cell attachment

Biomaterials Science ◽

10.1039/d0bm01454k ◽

2021 ◽

Author(s):

Yixia Yin ◽

Wenwu Wang ◽

Qi Shao ◽

Binbin Li ◽

Dan Yu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Neural Stem Cell ◽

Cell Attachment ◽

Injury Repair ◽

Cord Injury ◽

Proliferation Ability

A IKVAV-functionalized hydrogel is developed. It not only enhances neural stem cell (NSC) attachment, growth, and differentiation, but also maintains the proliferation ability of the NSC spheroids in the hydrogel for spinal cord injury repair.

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