Long-term survival, axonal growth-promotion, and myelination of Schwann cells grafted into contused spinal cord in adult rats

Xiaofei Wang, Xiao-Ming Xu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Schwann cells (SCs) have been considered to be one of the most promising cell types for transplantation to treat spinal cord injury (SCI) due to their unique growth-promoting properties. Despite the extensive use as donor cells for transplantation in SCI models, the fate of SCs is controversial due in part to the lack of a reliable marker for tracing the grafted SCs. To precisely assess the fate and temporal profile of transplanted SCs, we isolated purified SCs from sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP were directly injected into the epicenter of a moderate contusive SCI at the mid-thoracic level at 1. week post-injury. The number of SCs-GFP or SCs-GFP labeled with Bromodeoxyuridine (BrdU) was quantified at 5. min, 1. day, and 1, 2, 4, 12 and 24. weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, footfall error, thermal withdrawal latency, and footprint analysis were performed before and after the SCs-GFP transplantation. After transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival of grafted SCs-GFP up to 24. weeks post-grafting was observed with clearly identified SC individuals. SCs-GFP proliferated after injection, peaked at 2. weeks (26% of total SCs-GFP), decreased thereafter, and ceased at 12. weeks post-grafting. Although grafted SCs-GFP were mainly confined within the border of surrounding host tissue, they migrated along the central canal for up to 5.0. mm at 4. weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP). Within the SCs-GFP grafts, new blood vessels were formed. Except for a significant decrease of angle of rotation in the footprint analysis, we did not observe significant behavioral improvements in BBB locomotor rating scale, thermal withdrawal latency, or footfall errors, compared to the control animals that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well, proliferate, migrate along the central canal, and myelinate regenerated axons when being grafted into a clinically-relevant contusive SCI in adult rats. Combinatorial strategies, however, are essential to achieve a more meaningful functional regeneration of which SCs may play a significant role.

Original languageEnglish
Pages (from-to)308-319
Number of pages12
JournalExperimental Neurology
Volume261
DOIs
StatePublished - 2014

Fingerprint

Contusions
Schwann Cells
Spinal Cord
Growth
Spinal Cord Injuries
Cell Transplantation
Axons
Hot Temperature
Myelin P0 Protein
Transgenic Rats
Injections

Keywords

  • Functional recovery
  • Migration
  • Myelination
  • Proliferation
  • Schwann cells
  • Spinal cord injury
  • Survival

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Medicine(all)

Cite this

@article{321b9e896a054b9696f301141899afde,
title = "Long-term survival, axonal growth-promotion, and myelination of Schwann cells grafted into contused spinal cord in adult rats",
abstract = "Schwann cells (SCs) have been considered to be one of the most promising cell types for transplantation to treat spinal cord injury (SCI) due to their unique growth-promoting properties. Despite the extensive use as donor cells for transplantation in SCI models, the fate of SCs is controversial due in part to the lack of a reliable marker for tracing the grafted SCs. To precisely assess the fate and temporal profile of transplanted SCs, we isolated purified SCs from sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP were directly injected into the epicenter of a moderate contusive SCI at the mid-thoracic level at 1. week post-injury. The number of SCs-GFP or SCs-GFP labeled with Bromodeoxyuridine (BrdU) was quantified at 5. min, 1. day, and 1, 2, 4, 12 and 24. weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, footfall error, thermal withdrawal latency, and footprint analysis were performed before and after the SCs-GFP transplantation. After transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival of grafted SCs-GFP up to 24. weeks post-grafting was observed with clearly identified SC individuals. SCs-GFP proliferated after injection, peaked at 2. weeks (26{\%} of total SCs-GFP), decreased thereafter, and ceased at 12. weeks post-grafting. Although grafted SCs-GFP were mainly confined within the border of surrounding host tissue, they migrated along the central canal for up to 5.0. mm at 4. weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP). Within the SCs-GFP grafts, new blood vessels were formed. Except for a significant decrease of angle of rotation in the footprint analysis, we did not observe significant behavioral improvements in BBB locomotor rating scale, thermal withdrawal latency, or footfall errors, compared to the control animals that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well, proliferate, migrate along the central canal, and myelinate regenerated axons when being grafted into a clinically-relevant contusive SCI in adult rats. Combinatorial strategies, however, are essential to achieve a more meaningful functional regeneration of which SCs may play a significant role.",
keywords = "Functional recovery, Migration, Myelination, Proliferation, Schwann cells, Spinal cord injury, Survival",
author = "Xiaofei Wang and Xiao-Ming Xu",
year = "2014",
doi = "10.1016/j.expneurol.2014.05.022",
language = "English",
volume = "261",
pages = "308--319",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Long-term survival, axonal growth-promotion, and myelination of Schwann cells grafted into contused spinal cord in adult rats

AU - Wang, Xiaofei

AU - Xu, Xiao-Ming

PY - 2014

Y1 - 2014

N2 - Schwann cells (SCs) have been considered to be one of the most promising cell types for transplantation to treat spinal cord injury (SCI) due to their unique growth-promoting properties. Despite the extensive use as donor cells for transplantation in SCI models, the fate of SCs is controversial due in part to the lack of a reliable marker for tracing the grafted SCs. To precisely assess the fate and temporal profile of transplanted SCs, we isolated purified SCs from sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP were directly injected into the epicenter of a moderate contusive SCI at the mid-thoracic level at 1. week post-injury. The number of SCs-GFP or SCs-GFP labeled with Bromodeoxyuridine (BrdU) was quantified at 5. min, 1. day, and 1, 2, 4, 12 and 24. weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, footfall error, thermal withdrawal latency, and footprint analysis were performed before and after the SCs-GFP transplantation. After transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival of grafted SCs-GFP up to 24. weeks post-grafting was observed with clearly identified SC individuals. SCs-GFP proliferated after injection, peaked at 2. weeks (26% of total SCs-GFP), decreased thereafter, and ceased at 12. weeks post-grafting. Although grafted SCs-GFP were mainly confined within the border of surrounding host tissue, they migrated along the central canal for up to 5.0. mm at 4. weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP). Within the SCs-GFP grafts, new blood vessels were formed. Except for a significant decrease of angle of rotation in the footprint analysis, we did not observe significant behavioral improvements in BBB locomotor rating scale, thermal withdrawal latency, or footfall errors, compared to the control animals that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well, proliferate, migrate along the central canal, and myelinate regenerated axons when being grafted into a clinically-relevant contusive SCI in adult rats. Combinatorial strategies, however, are essential to achieve a more meaningful functional regeneration of which SCs may play a significant role.

AB - Schwann cells (SCs) have been considered to be one of the most promising cell types for transplantation to treat spinal cord injury (SCI) due to their unique growth-promoting properties. Despite the extensive use as donor cells for transplantation in SCI models, the fate of SCs is controversial due in part to the lack of a reliable marker for tracing the grafted SCs. To precisely assess the fate and temporal profile of transplanted SCs, we isolated purified SCs from sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP were directly injected into the epicenter of a moderate contusive SCI at the mid-thoracic level at 1. week post-injury. The number of SCs-GFP or SCs-GFP labeled with Bromodeoxyuridine (BrdU) was quantified at 5. min, 1. day, and 1, 2, 4, 12 and 24. weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, footfall error, thermal withdrawal latency, and footprint analysis were performed before and after the SCs-GFP transplantation. After transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival of grafted SCs-GFP up to 24. weeks post-grafting was observed with clearly identified SC individuals. SCs-GFP proliferated after injection, peaked at 2. weeks (26% of total SCs-GFP), decreased thereafter, and ceased at 12. weeks post-grafting. Although grafted SCs-GFP were mainly confined within the border of surrounding host tissue, they migrated along the central canal for up to 5.0. mm at 4. weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP). Within the SCs-GFP grafts, new blood vessels were formed. Except for a significant decrease of angle of rotation in the footprint analysis, we did not observe significant behavioral improvements in BBB locomotor rating scale, thermal withdrawal latency, or footfall errors, compared to the control animals that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well, proliferate, migrate along the central canal, and myelinate regenerated axons when being grafted into a clinically-relevant contusive SCI in adult rats. Combinatorial strategies, however, are essential to achieve a more meaningful functional regeneration of which SCs may play a significant role.

KW - Functional recovery

KW - Migration

KW - Myelination

KW - Proliferation

KW - Schwann cells

KW - Spinal cord injury

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=84905465777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905465777&partnerID=8YFLogxK

U2 - 10.1016/j.expneurol.2014.05.022

DO - 10.1016/j.expneurol.2014.05.022

M3 - Article

C2 - 24873728

AN - SCOPUS:84905465777

VL - 261

SP - 308

EP - 319

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

ER -