Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury

Hideaki Nakajima, Kenzo Uchida, Alexander R. Guerrero, Shuji Watanabe, Daisuke Sugita, Naoto Takeura, Ai Yoshida, Guang Long, Karina T. Wright, William E.B. Johnson, Hisatoshi Baba

Research output: Contribution to journalArticle

Abstract

Abstract Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-a and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.
Original languageEnglish
Pages (from-to)1614-1625
Number of pages12
JournalJournal of Neurotrauma
Volume29
Issue number8
Early online date1 Jan 2012
DOIs
Publication statusPublished - 20 May 2012

Fingerprint

Mesenchymal Stem Cell Transplantation
Macrophage Activation
Spinal Cord Injuries
Mesenchymal Stromal Cells
Macrophages
Phenotype
Cicatrix
Arginase
Interleukin-13
Contusions
Locomotion
Myelin Sheath
Neuroglia
Interleukin-4
Axons
Interleukin-6
Spinal Cord
Transplantation
Bone Marrow
Inflammation

Cite this

Nakajima, Hideaki ; Uchida, Kenzo ; Guerrero, Alexander R. ; Watanabe, Shuji ; Sugita, Daisuke ; Takeura, Naoto ; Yoshida, Ai ; Long, Guang ; Wright, Karina T. ; Johnson, William E.B. ; Baba, Hisatoshi. / Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. In: Journal of Neurotrauma. 2012 ; Vol. 29, No. 8. pp. 1614-1625.
@article{cb12ec1efcd3451b8b647bf20a763023,
title = "Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury",
abstract = "Abstract Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-a and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.",
author = "Hideaki Nakajima and Kenzo Uchida and Guerrero, {Alexander R.} and Shuji Watanabe and Daisuke Sugita and Naoto Takeura and Ai Yoshida and Guang Long and Wright, {Karina T.} and Johnson, {William E.B.} and Hisatoshi Baba",
year = "2012",
month = "5",
day = "20",
doi = "10.1089/neu.2011.2109",
language = "English",
volume = "29",
pages = "1614--1625",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "8",

}

Nakajima, H, Uchida, K, Guerrero, AR, Watanabe, S, Sugita, D, Takeura, N, Yoshida, A, Long, G, Wright, KT, Johnson, WEB & Baba, H 2012, 'Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury', Journal of Neurotrauma, vol. 29, no. 8, pp. 1614-1625. https://doi.org/10.1089/neu.2011.2109

Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. / Nakajima, Hideaki; Uchida, Kenzo; Guerrero, Alexander R.; Watanabe, Shuji; Sugita, Daisuke; Takeura, Naoto; Yoshida, Ai; Long, Guang; Wright, Karina T.; Johnson, William E.B.; Baba, Hisatoshi.

In: Journal of Neurotrauma, Vol. 29, No. 8, 20.05.2012, p. 1614-1625.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury

AU - Nakajima, Hideaki

AU - Uchida, Kenzo

AU - Guerrero, Alexander R.

AU - Watanabe, Shuji

AU - Sugita, Daisuke

AU - Takeura, Naoto

AU - Yoshida, Ai

AU - Long, Guang

AU - Wright, Karina T.

AU - Johnson, William E.B.

AU - Baba, Hisatoshi

PY - 2012/5/20

Y1 - 2012/5/20

N2 - Abstract Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-a and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.

AB - Abstract Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-a and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.

UR - http://www.scopus.com/inward/record.url?scp=84861689886&partnerID=8YFLogxK

UR - http://online.liebertpub.com/doi/abs/10.1089/neu.2011.2109

U2 - 10.1089/neu.2011.2109

DO - 10.1089/neu.2011.2109

M3 - Article

C2 - 22233298

VL - 29

SP - 1614

EP - 1625

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 8

ER -