Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury

Lu, Paul; Wang, Yaozhi; Graham, Lori; McHale, Karla; Gao, Mingyong; Wu, Di; Brock, J. H.; Blesch, Armin; Rosenzweig, E; Havton, Leif A.; Zheng, Binhai; Conner, J. M.; Maršala, Martin; Tuszynski, Mark H.

doi:10.1016/j.cell.2012.08.020

Cited by 775 publications

(846 citation statements)

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“…In recent years, more attention has been shifted to enhancing the intrinsic growth capacity of adult central nervous system axons. Deletion of pTEN (phosphatase and tensin homolog) induces unprecedented regeneration across the fully-transacted spinal cord [3] .Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] .…”

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confidence: 99%

“…Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] .…”

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An update on spinal cord injury research

Zou

2013

Neurosci. Bull.

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Spinal cord injury (SCI) is an ever-increasing challenge.Severe injury can cause long-term loss of sensory and motor functions, as well as other chronic conditions, such as neuropathic pain and autonomic dysreflexia. So far, most research has been focused on acute injury. However, due to the lack of treatment, more and more individuals with this condition enter a chronic state, to which very little research effort has been dedicated. SCI is a complex condition. It involves damage to axons, death of neurons, neuroinflammation, glial scar formation, loss of myelin, and lack of remyelination. It is clear that effective treatment will require combinatorial approaches. The 12 invited articles for this special issue on SCI provide an update on many of these areas of SCI research. Here, I highlight the articles and reviews by theme.Severe SCI involves severing of axons, breaking ascending and descending connections. Inhibitory molecules in the environment of the adult central nervous system, such as the myelin-associated inhibitors and proteoglycans in glial scars, were thought to be the major cause of the lack of regeneration for many years [1] .However, efforts to regenerate axons across a lesion site in the mammalian spinal cord by overcoming this inhibition have not been successful. In some cases, axon regeneration into cell grafts can be achieved, as in studies using preconditioning lesion paradigms of sensory axons [2] .But few axons project beyond the lesion and reach longrange targets. In recent years, more attention has been shifted to enhancing the intrinsic growth capacity of adult central nervous system axons. Deletion of pTEN (phosphatase and tensin homolog) induces unprecedented regeneration across the fully-transacted spinal cord [3] .Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] . Molecular mechanisms that promote or inhibit axon growth have been studied, using various injury paradigms, in different neuronal types and species. Some species have poor central regeneration, whereas others have the capacity to regenerate. Axons in the peripheral nervous system of mammals also show extensive regeneration. The review by Martin Oudega of the University of Pittsburgh [7] provides a comprehensive discussion comparing the molecular mechanisms found in mammals and zebrafish.These comparisons allow for a better understanding of the underlying principles. Remarkably, regeneration in the zebrafish central nervous system is also incomplete. Some axon tracts can regenerate but others cannot. This makes zebrafish an interesting model system for SCI research along with the ...

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An update on spinal cord injury research

Zou

2013

Neurosci. Bull.

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“…Tuszynski has showed how well stem cells can work -at least, in animal models 1 . His group implanted neural stem cells derived from human fetal tissue into rats with severe spinal-cord injuries.…”

Section: Scar Tissuementioning

confidence: 99%

Neuroscience: New nerves for old

Bourzac¹

2016

Nature

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“…Thus, the use of “neuronal relay” strategy to repair the injured spinal cord has received increasing recognition2, 8 in recent years. When stem cells were combined with biomaterials supporting sustained release of neurotrophic factors, it is believed that the postinjury microenvironment could be improved, allowing longer axonal growth and more synaptic connections with the host neurons 9. However, safety issue remains a major concern for direct transplantation of stem cells into the spinal cord because of the possibility of migration and ectopic proliferation, and the uncertainty of the differentiation of the grafted cells 10…”

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confidence: 99%

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

et al. 2018

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Tissue engineering–based neural construction holds promise in providing organoids with defined differentiation and therapeutic potentials. Here, a bioengineered transplantable spinal cord–like tissue (SCLT) is assembled in vitro by simulating the white matter and gray matter composition of the spinal cord using neural stem cell–based tissue engineering technique. Whether the organoid would execute targeted repair in injured spinal cord is evaluated. The integrated SCLT, assembled by white matter–like tissue (WMLT) module and gray matter–like tissue (GMLT) module, shares architectural, phenotypic, and functional similarities to the adult rat spinal cord. Organotypic coculturing with the dorsal root ganglion or muscle cells shows that the SCLT embraces spinal cord organogenesis potentials to establish connections with the targets, respectively. Transplantation of the SCLT into the transected spinal cord results in a significant motor function recovery of the paralyzed hind limbs in rats. Additionally, targeted spinal cord tissue repair is achieved by the modular design of SCLT, as evidenced by an increased remyelination in the WMLT area and an enlarged innervation in the GMLT area. More importantly, the pro‐regeneration milieu facilitates the formation of a neuronal relay by the donor neurons, allowing the conduction of descending and ascending neural inputs.

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Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury

Cited by 775 publications

References 43 publications

An update on spinal cord injury research

An update on spinal cord injury research

Neuroscience: New nerves for old

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

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