Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury
Open Access
- 8 January 2013
- journal article
- Published by Springer Science and Business Media LLC in Molecular Brain
- Vol. 6 (1), 3
- https://doi.org/10.1186/1756-6606-6-3
Abstract
Background: The transplantation of neural stem/progenitor cells (NS/PCs) at the sub-acute phase of spinal cord injury, but not at the chronic phase, can promote functional recovery. However, the reasons for this difference and whether it involves the survival and/or fate of grafted cells under these two conditions remain unclear. To address this question, NS/PC transplantation was performed after contusive spinal cord injury in adult mice at the sub-acute and chronic phases. Results: Quantitative analyses using bio-imaging, which can noninvasively detect surviving grafted cells in living animals, revealed no significant difference in the survival rate of grafted cells between the sub-acute and chronic transplantation groups. Additionally, immunohistology revealed no significant difference in the differentiation phenotypes of grafted cells between the two groups. Microarray analysis revealed no significant differences in the expression of genes encoding inflammatory cytokines or growth factors, which affect the survival and/or fate of grafted cells, in the injured spinal cord between the sub-acute and chronic phases. By contrast, the distribution of chronically grafted NS/PCs was restricted compared to NS/PCs grafted at the sub-acute phase because a more prominent glial scar located around the lesion epicenter enclosed the grafted cells. Furthermore, microarray and histological analysis revealed that the infiltration of macrophages, especially M2 macrophages, which have anti-inflammatory role, was significantly higher at the sub-acute phase than the chronic phase. Ultimately, NS/PCs that were transplanted in the sub-acute phase, but not the chronic phase, promoted functional recovery compared with the vehicle control group. Conclusions: The extent of glial scar formation and the characteristics of inflammation is the most remarkable difference in the injured spinal cord microenvironment between the sub-acute and chronic phases. To achieve functional recovery by NS/PC transplantation in cases at the chronic phase, modification of the microenvironment of the injured spinal cord focusing on glial scar formation and inflammatory phenotype should be considered.Keywords
This publication has 60 references indexed in Scilit:
- Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cordExperimental Neurology, 2003
- Hepatocyte growth factor promotes proliferation and neuronal differentiation of neural stem cells from mouse embryosMolecular and Cellular Neuroscience, 2003
- Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytesTrends in Immunology, 2002
- Transplantation of in vitro‐expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult ratsJournal of Neuroscience Research, 2002
- Evaluation of in vitro proliferative activity of human fetal neural stem/progenitor cells using indirect measurements of viable cells based on cellular metabolic activityJournal of Neuroscience Research, 2002
- Advances in In Vivo Bioluminescence Imaging of Gene ExpressionAnnual Review of Biomedical Engineering, 2002
- Chondroitinase ABC promotes functional recovery after spinal cord injuryNature, 2002
- A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applicationsNature Biotechnology, 2002
- Motor discoordination in mutant mice heterozygous for the type 1 inositol 1,4,5-trisphosphate receptorBehavioural Brain Research, 2001
- Pluripotent Stem Cells Engrafted into the Normal or Lesioned Adult Rat Spinal Cord Are Restricted to a Glial LineageExperimental Neurology, 2001