‘Surface Transplantation’ for Nerve Injury and Repair: The Quest for Minimally Invasive Cell Delivery

Cell transplantation is an ambitious, but arguably realistic, therapy for repair of the nervous system. Cell delivery is a major challenge for clinical translation, especially given the apparently inhibitory astrogliotic environment in degenerated tissue. However, astrogliotic tissue also contains e...

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Bibliographic Details
Published in:Trends in neurosciences (Regular ed.) 2018-07, Vol.41 (7), p.429-441
Main Authors: Sekiya, Tetsuji, Holley, Matthew C.
Format: Article
Language:English
Subjects:
Animals
astrocyte scar
cell transplantation
Cell Transplantation - methods
Humans
nerve injury
Nerve Regeneration - physiology
Neurodegenerative Diseases - physiopathology
Neurodegenerative Diseases - therapy
neurodegenerative disorders
reactive astrocyte
surface transplantation
Trauma, Nervous System - physiopathology
Trauma, Nervous System - therapy
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Summary:Cell transplantation is an ambitious, but arguably realistic, therapy for repair of the nervous system. Cell delivery is a major challenge for clinical translation, especially given the apparently inhibitory astrogliotic environment in degenerated tissue. However, astrogliotic tissue also contains endogenous structural and biochemical cues that can be harnessed for functional repair. Minimizing damage to these cues during cell delivery could enhance cell integration. This theory is supported by studies with an auditory astrocyte scar model, in which cells delivered onto the surface of the damaged nerve were more successfully integrated in the host than those injected into the tissue. We consider the application of this less invasive approach for nerve injury and its potential application to some neurodegenerative disorders. Compression injury to the auditory nerve causes auditory spiral ganglion cell death and cochlear nucleus cell death. Subsequently, reactive astrocytes project numerous processes into the peripheral portion of the nerve (the astrocyte outgrowth). Donor cells transplanted on the surface of the astrocyte outgrowth can autonomously enter the nerve, migrate, and integrate into the host, leading to functional restoration. In contrast, when donor cells are injected into the nerve, they die. Important structural and biochemical cues for axon regeneration embedded in the host can be harnessed by donor cells only when they are transplanted onto the surface of the host, without disturbing astrogliosis/astrocyte scar. We hypothesize that surface transplantation may be applied, not only for motor neuron diseases, but also for Alzheimer’s disease and Parkinson’s disease, in which the lesions lie deeper within the central nervous system.
ISSN:0166-2236
1878-108X
DOI:10.1016/j.tins.2018.03.008