Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury

Mousumi Ghosh, Luis M. Tuesta, Rocio Puentes, Samik Patel, Kiara Melendez, Abderrahman El Maarouf, Urs Rutishauser, Damien D Pearse

Research output: Contribution to journalArticle

64 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)979-992
Number of pages14
JournalGLIA
Volume60
Issue number6
DOIs
StatePublished - May 1 2012

Fingerprint

Schwann Cells
Green Fluorescent Proteins
Spinal Cord Injuries
Cell Movement
Axons
Regeneration
Growth
Surface Properties
polysialic acid
Injections
Wounds and Injuries

Keywords

  • Axon regeneration
  • Cell transplantation
  • Functional recovery
  • Migration
  • Scar

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury. / Ghosh, Mousumi; Tuesta, Luis M.; Puentes, Rocio; Patel, Samik; Melendez, Kiara; El Maarouf, Abderrahman; Rutishauser, Urs; Pearse, Damien D.

In: GLIA, Vol. 60, No. 6, 01.05.2012, p. 979-992.

Research output: Contribution to journalArticle

Ghosh, Mousumi ; Tuesta, Luis M. ; Puentes, Rocio ; Patel, Samik ; Melendez, Kiara ; El Maarouf, Abderrahman ; Rutishauser, Urs ; Pearse, Damien D. / Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury. In: GLIA. 2012 ; Vol. 60, No. 6. pp. 979-992.
@article{525b715893694d0b90ca28150f925984,
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.",
keywords = "Axon regeneration, Cell transplantation, Functional recovery, Migration, Scar",
author = "Mousumi Ghosh and Tuesta, {Luis M.} and Rocio Puentes and Samik Patel and Kiara Melendez and {El Maarouf}, Abderrahman and Urs Rutishauser and Pearse, {Damien D}",
year = "2012",
month = "5",
day = "1",
doi = "10.1002/glia.22330",
language = "English",
volume = "60",
pages = "979--992",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury

AU - Ghosh, Mousumi

AU - Tuesta, Luis M.

AU - Puentes, Rocio

AU - Patel, Samik

AU - Melendez, Kiara

AU - El Maarouf, Abderrahman

AU - Rutishauser, Urs

AU - Pearse, Damien D

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

KW - Axon regeneration

KW - Cell transplantation

KW - Functional recovery

KW - Migration

KW - Scar

UR - http://www.scopus.com/inward/record.url?scp=84859700129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859700129&partnerID=8YFLogxK

U2 - 10.1002/glia.22330

DO - 10.1002/glia.22330

M3 - Article

C2 - 22460918

AN - SCOPUS:84859700129

VL - 60

SP - 979

EP - 992

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 6

ER -