Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury Journal Article
| Authors: | Ghosh, M.; Tuesta, L. M.; Puentes, R.; Patel, S.; Melendez, K.; El-Maarouf, A. ; Rutishauser, U.; Pearse, D. D. |
| Article Title: | Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury |
| Abstract: | Schwann cell (SC) implantation after spinal cord injury (SCI) promotes axonal regeneration, remyelination repair, and functional recovery. Reparative efficacy, however, may be limited because of the inability of SCs to migrate outward from the lesion-implant site. Altering SC cell surface properties by overexpressing polysialic acid (PSA) has been shown to promote SC migration. In this study, a SCI contusion model was used to evaluate the migration, supraspinal axon growth support, and functional recovery associated with polysialyltransferase (PST)-overexpressing SCs [PST-green fluorescent protein (GFP) SCs] or controls (GFP SCs). Compared with GFP SCs, which remained confined to the injection site at the injury center, PST-GFP SCs migrated across the lesion:host cord interface for distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP SCs, there was extensive serotonergic and corticospinal axon in-growth within the implants that was limited in the GFP SC controls. The enhanced migration of PST-GFP SCs was accompanied by significant growth of these axons caudal to lesion. Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the open-field and on the gridwalk test, beyond the modest improvements provided by GFP SC controls. This study for the first time demonstrates that a lack of migration by SCs may hinder their reparative benefits and that cell surface overexpression of PSA enhances the ability of implanted SCs to associate with and support the growth of corticospinal axons. These results provide further promise that PSA-modified SCs will be a potent reparative approach for SCI. © 2012 Wiley Periodicals, Inc. |
| Keywords: | controlled study; protein expression; treatment outcome; implant; recovery of function; unclassified drug; nonhuman; linear models; animal cell; animals; animal tissue; cell function; green fluorescent protein; animal experiment; animal model; time factors; luminescent proteins; bacterial proteins; dextrans; polysialic acid; rat; cell migration; cell movement; green fluorescent proteins; cell count; rats; schwann cell; disease models, animal; psychomotor performance; migration; nerve regeneration; spinal cord injury; spinal cord injuries; cell transplantation; scar; sialic acids; biotin; serotonin; rats, inbred f344; cell surface; schwann cells; sciatic nerve; pyramidal tract; transferase; nerve fiber growth; nerve fiber regeneration; functional recovery; axon regeneration; exploratory behavior; open field test; polysialyltransferase; astrocytosis; remyelinization; schwann cell implant; serotoninergic nerve cell |
| Journal Title: | Glia |
| Volume: | 60 |
| Issue: | 6 |
| ISSN: | 0894-1491 |
| Publisher: | John Wiley & Sons, Inc. |
| Date Published: | 2012-05-01 |
| Start Page: | 979 |
| End Page: | 992 |
| Language: | English |
| DOI: | 10.1002/glia.22330 |
| PROVIDER: | scopus |
| PUBMED: | 22460918 |
| PMCID: | PMC4387847 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "CODEN: GLIAE" - "Source: Scopus" |
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