Induced expression of polysialic acid in the spinal cord promotes regeneration of sensory axons

Use of PSA-NCAM in Repair of the Central Nervous System

“…A similar approach was used to augment the sprouting response of Purkinjie cells in lesioned cerebellum [37], and the growth of sensory axons into a spinal lesion cavity, with some axons growing across the cavity and extending into the rostral cord [38]. In this study, regeneration of Purkinje axons was additionally stimulated by GAP-43 and L1 over-expression, and regrowth of spinal sensory fibers was prepotentiated by a peripheral nerve-conditioning lesion.…”

“…To achieve this sustained expression at the site of a spinal cord injury, the HIV(ALSV-A) virus/GFAP-TVA transgenic system [35,36] was used to selectively infect astrocytes with the gene encoding the PST (Sia8IV) polysialyltransferase. A sustainable high level of PSA expression was observed on these cells for over 6 weeks, and nearly 10% of lesioned, corticospinal fibers were able to regrow completely through the injury site [24,25,37,38]. In addition, the engineered expression of PSA on grafted Schwann cells appears to enhance their regeneration promoting effect (c) [37,42].…”

“…In this study, regeneration of Purkinje axons was additionally stimulated by GAP-43 and L1 over-expression, and regrowth of spinal sensory fibers was prepotentiated by a peripheral nerve-conditioning lesion. Although the viral gene delivery system used in these studies was not engineered to specifically target astrocytes, the PSA expression obtained included large numbers of these cells [37,38]. However, it is possible that the contribution of PSA in these studies also reflects other cell types.…”

In Vivo Evaluation of Polysialic Acid as Part of Tissue-Engineered Nerve Transplants

“…8 Recent in vivo studies demonstrated that artificial induction of polySia expression reinforces the regenerative capacity, for example, in adult mouse brain and after spinal cord or peripheral nerve injury. 1,[9][10][11][12][13] polySia provides several outstanding features that make it a highly attractive building block for tissue-engineered nerve grafts. It is supposed to be highly biocompatible and stable in mammals, where highly specific degradation of polySia can only be induced by phage-born endosialidases (endo-N-acetylneuraminidase).…”

Enzymatic Engineering of Polysialic Acid on Cells in Vitro and in Vivo Using a Purified Bacterial Polysialyltransferase

“…We and others have shown that reintroduction of PSA expression in the lesioned adult nervous system can restore some plasticity and thereby facilitate repair mechanisms. For example, overexpression of the polysialyltransferase gene in vivo promotes regeneration of lesioned axons and recruitment of neural progenitors into lesions (17)(18)(19)(20). Similarly, introduction of the gene into cells in culture has improved cell grafting therapies using Schwann cells in spinal cord injury (21)(22)(23)(24) or stem cell-derived progenitors (for review, see Ref.…”