Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury

doi:10.1073/pnas.0603747103

Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury

*Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel; and
^‡Neuroimmunology Unit (DIBIT), Department of Neurology and Neurophysiology, San Raffaele Hospital, Via Olgettina 58, 20132 Milano, Italy

Edited by Michael Sela, Weizmann Institute of Science, Rehovot, Israel, and approved July 11, 2006
↵ ^†Y.Z. and H.A. contributed equally to this work. (received for review May 10, 2006)

Abstract

The well regulated activities of microglia and T cells specific to central nervous system (CNS) antigens can contribute to the protection of CNS neural cells and their renewal from adult neural stem/progenitor cells (aNPCs). Here we report that T cell-based vaccination of mice with a myelin-derived peptide, when combined with transplantation of aNPCs into the cerebrospinal fluid (CSF), synergistically promoted functional recovery after spinal cord injury. The synergistic effect was correlated with modulation of the nature and intensity of the local T cell and microglial response, expression of brain-derived neurotrophic factor and noggin protein, and appearance of newly formed neurons from endogenous precursor-cell pools. These results substantiate the contention that the local immune response plays a crucial role in recruitment of aNPCs to the lesion site, and suggest that similar immunological manipulations might also serve as a therapeutic means for controlled migration of stem/progenitor cells to other acutely injured CNS sites.

Footnotes

^§To whom correspondence should be addressed. E-mail: michal.schwartz{at}weizmann.ac.il
Author contributions: Y.Z., H.A., S.P., G.M., and M.S. designed research; Y.Z., H.A., and M.S. performed research; S.P. and G.M. contributed new reagents/analytic tools; Y.Z., H.A., and M.S. analyzed data; and Y.Z., H.A., and M.S. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

SCI,

spinal cord injury;

aNPCs,

adult neural stem/progenitor cells;

CFA,

complete Freund’s adjuvant;

MOG,

myelin oligodendrocyte glycoprotein;

BMS,

Basso mouse scale;

OVA,

ovalbumin;

DCX,

doublecortin;

GFAP,

glial fibrillary acidic protein;

BDNF,

brain-derived neurotrophic factor.