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Transplantation of Olfactory Ensheathing Cells in Spinal Cord Injury

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Cellular Therapy for Stroke and CNS Injuries

Abstract

Spinal cord injury is characterized by massive cellular and axonal loss, a neurotoxic environment, inhibitory molecules and physical barriers that hamper nerve regeneration and reconnection leading to chronic paralysis. Transplantation of different types of cells is one of the strategies being examined in order to restore the lost cell populations and to re-establish a permissive environment for nerve regeneration. The mammalian olfactory system is one of the few zones in the body where neurogenesis occurs during the lifetime of the organism, with olfactory neurons being replaced daily with their axons elongating from the peripheral nervous system into the central nervous system to re-establish functional connections. The regenerative ability of this system is largely attributed to the presence of a unique group of cells called olfactory ensheathing cells (OECs). OECs have emerged as an encouraging cell candidate for transplantation therapies to repair the injured spinal cord with multiple animal models showing significant functional improvements and several human trials establishing that the procedure is safe and feasible. Even though the results are promising with some animal models showing remarkable restoration of function, the variability amongst studies in terms of outcome assessments, cell purity, cell culture and transplantation protocols make it difficult to reach firm conclusions about the effectiveness of OEC transplant therapy to treat the injured spinal cord. These variations need to be addressed in order to achieve a more realistic understanding of how the benefits of OEC transplantation enhance the therapeutic outcomes.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

cAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

CP:

Cribriform plate

CSPG:

Chondroitin sulfate proteoglycan

DAPI:

4’,6-diamidino-2-phenylindole

dBcAMP:

Dibutyryl cyclic adenosine monophosphate

FGF:

Fibroblast growth factor

GDNF:

Glial cell-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

GL:

Glomerular layer

HNK-1:

Human natural killer-1

IGF:

Insulin-like growth factor

LP:

Lamina propria

MAG:

Myelin associated glycoprotein

NFL:

Nerve fibre layer

NGF:

Nerve growth factor

Nogo:

Neurite outgrowth inhibitory protein

NPY:

Neuropeptide Y

NT4:

Neurotrophin 4

NT5:

Neurotrophin 5

OE:

Olfactory epithelium

OEC:

Olfactory ensheathing cell

OMgp:

Oligodendrocyte-myelin glycoprotein

p75NTR :

p75 low-affinity neurotrophin receptor

PNS:

Peripheral nervous system

SCI:

Spinal cord injury

TROY:

TNFRSF expressed on the mouse embryo

VEGF:

Vascular endothelial growth factor

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Tello Velasquez, J., Ekberg, J., St John, J. (2015). Transplantation of Olfactory Ensheathing Cells in Spinal Cord Injury. In: Zhao, LR., Zhang, J. (eds) Cellular Therapy for Stroke and CNS Injuries. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-11481-1_13

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