当前位置： SCI文献检索 > JOURNAL OF THE NEUROLOGICAL SCIENCES期刊下所有文献 > Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC.

Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC.

Abstract：

:A multitude of factors must be overcome following spinal cord injury (SCI) in order to achieve clinical improvement in patients. It is thought that by combining promising therapies these diverse factors could be combatted with the aim of producing an overall improvement in function. Chondroitin sulphate proteoglycans (CSPGs) present in the glial scar that forms following SCI present a significant block to axon regeneration. Digestion of CSPGs by chondroitinase ABC (ChABC) leads to axon regeneration, neuronal plasticity and functional improvement in preclinical models of SCI. However, the enzyme activity decays at body temperature within 24-72h, limiting the translational potential of ChABC as a therapy. Olfactory ensheathing cells (OECs) have shown huge promise as a cell transplant therapy in SCI. Their beneficial effects have been demonstrated in multiple small animal SCI models as well as in naturally occurring SCI in canine patients. In the present study, we have genetically modified canine OECs from the mucosa to constitutively produce enzymatically active ChABC. We have developed a lentiviral vector that can deliver a mammalian modified version of the ChABC gene to mammalian cells, including OECs. Enzyme production was quantified using the Morgan-Elson assay that detects the breakdown products of CSPG digestion in cell supernatants. We confirmed our findings by immunolabelling cell supernatant samples using Western blotting. OECs normal cell function was unaffected by genetic modification as demonstrated by normal microscopic morphology and the presence of the low affinity neurotrophin receptor (p75(NGF)) following viral transduction. We have developed the means to allow production of active ChABC in combination with a promising cell transplant therapy for SCI repair.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Carwardine D,Wong LF,Fawcett JW,Muir EM,Granger N

doi

10.1016/j.jns.2016.06.011

subject

Has Abstract

pub_date

2016-08-15 00:00:00

pages

311-8

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(16)30342-2

journal_volume

367

pub_type

杂志文章

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