Use of polysialic acid in repair of the central nervous system

Abstract

Polysialic acid (PSA), a large cell-surface carbohydrate that regulates cell interactions, is used during vertebrate development to promote precursor cell migration and axon path-finding. The induction of PSA expression in damaged adult CNS tissues could help them to rebuild by creating conditions permissive for architectural remodeling. This possibility has been explored in two contexts, the regeneration of axons and the recruitment of endogenous neural precursors to a lesion. Glial scars that form at CNS injury sites block axon regeneration. It has been found that transfection of scar astrocytes by a viral vector encoding polysialyltransferase leads to sustained expression of high levels of PSA. With this treatment, a substantial portion of severed corticospinal tract axon processes were able to grow through a spinal injury site. In the studies of precursor cell migration to a cortical lesion, it was found that induced PSA expression in a path extending from the subventricular zone to a lesion near the cortical surface increased recruitment of BrdU͞nestin-positive cells along the path and into the injury site. These displaced precursors were able to differentiate in a regionally appropriate manner. These findings suggest that induced PSA expression can be used as a strategy for promoting tissue repair involving both replacement of cells and rebuilding of neural connections.astrocyte ͉ axon regeneration ͉ brain lesions ͉ plasticity ͉ progenitor migration

Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis

“…20,21 In addition, postoperative glial scarring and radiotherapy may enhance the migration of endogenous neural SCs cells in the recurrent tumor. 22 Therefore, in a subset of recurrent glioblastomas (n ¼ 17), we used FACS analysis to sort the CD133-positive cells from freshly dissociated specimens. To rule out CD133-positive cells of hematopoietic origin, 31 the cells also were labeled with anti-CD45 (Fig.…”

“…19 Despite these results, there is no evidence that higher fractions of CD133-positive cells in glioblastoma that recurs after radiochemotherapy are correlated with a worse prognosis. It also remains to be determined whether and the extent to which the neural SCs that exhibit positive tropism both toward brain tumors and toward areas of brain inflammation [20][21][22] may affect the composition of the CD133-positive cell fraction of glioblastoma.…”

Improved Stem Cell-Derived Motoneuron Survival, Migration, Sprouting, and Innervation with Enhanced Expression of Polysialic Acid

“…The HB9::GFP ESC line was virally transduced using a lentiviral vector (pLenti, 6.5 × 10 5 IU/ml at 1:250; Invitrogen) carrying the mouse PST gene under control of the ubiquitous cytomegalovirus promoter (7,8,15). Blasticidinresistant cells were selected, propagated, and stocks stored in liquid nitrogen.…”

Enzyme-dependent Variations in the Polysialylation of the Neural Cell Adhesion Molecule (NCAM) in Vivo

“…In vertebrates, the neural cell adhesion molecule (NCAM) is the major acceptor of this unique carbohydrate, which is, intriguingly, attached post-translationally with high selectivity to glycans at the fifth and sixth N-glycosylation sites in the fifth immunoglobulin-like domain of NCAM (3)(4)(5)(6). NCAM is expressed on the membranes of neurons and glia cells both in developing and adult vertebrate organisms and regulates via homophilic and heterophilic interactions cell adhesion, signaling, migration, and plasticity in the central nervous system (7)(8)(9)(10)(11). Attachment of polySia to NCAM greatly influences its properties, because the bulky and highly negatively charged carbohydrate moiety increases intermembrane space, impedes the close approach and adhesion between adjacent cells and, therefore, facilitates cell motility and promotes neurogenesis, axon outgrowth as well as synaptic plasticity (1,(12)(13)(14)(15)(16)(17).…”