Adult bone marrow-derived mononuclear cells expressing chondroitinase AC transplanted into CNS injury sites promote local brain chondroitin sulphate degradation

Journal of Neuroscience Methods
Yvette M Coulson-ThomasMarimelia Porcionatto

Abstract

Injury to the CNS of vertebrates leads to the formation of a glial scar and production of inhibitory molecules, including chondroitin sulphate proteoglycans. Various studies suggest that the sugar component of the proteoglycan is responsible for the inhibitory role of these compounds in axonal regeneration. By degrading chondroitin sulphate chains with specific enzymes, denominated chondroitinases, the inhibitory capacity of these proteoglycans is decreased. Chondroitinase administration involves frequent injections of the enzyme at the lesion site which constitutes a rather invasive method. We have produced a vector containing the gene for Flavobacterium heparinum chondroitinase AC for expression in adult bone marrow-derived cells which were then transplanted into an injury site in the CNS. The expression and secretion of active chondroitinase AC was observed in vitro using transfected Chinese hamster ovarian and gliosarcoma cells and in vivo by immunohistochemistry analysis which showed degraded chondroitin sulphate coinciding with the location of transfected bone marrow-derived cells. Immunolabelling of the axonal growth-associated protein GAP-43 was observed in vivo and coincided with the location of degraded chondroitin su...Continue Reading

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Citations

Jul 19, 2011·Neurology Research International·Layla T GalindoMarimelia A Porcionatto
Aug 19, 2015·Experimental Neurology·Patrice D SmithJames W Fawcett
Jul 16, 2010·Developmental Neurobiology·Angela R FilousJerry Silver
May 26, 2012·The Journal of Comparative Neurology·Jae-Hyuk YiHerbert M Geller
Jul 16, 2013·Stem Cell Research·Thais R M FilippoMarimélia A Porcionatto
May 13, 2014·Cell Transplantation·Wise Young
May 10, 2017·Molecular Neurobiology·Layla T GalindoMarimelia Porcionatto
Sep 10, 2020·Frontiers in Cell and Developmental Biology·Sudan PuriVivien J Coulson-Thomas
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Laura N ZamproniMarimelia A Porcionatto
Sep 14, 2019·Journal of Medicinal Chemistry·Vinícius Barros Ribeiro da SilvaVinicius Toledo Ribas

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