Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain

M. C. Tate, D. A. Shear, S. W. Hoffman, D. G. Stein, D. R. Archer, M. C. LaPlaca*

*Corresponding author for this work

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons, astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (105 cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p lt; 0.01). At the longer survival times (3 weeks-3 months), 63-76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p lt; 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.

Original languageEnglish (US)
Pages (from-to)283-295
Number of pages13
JournalCell Transplantation
Volume11
Issue number3
StatePublished - Jul 2 2002

Fingerprint

Neural Stem Cells
Stem cells
Fibronectins
Brain
Transplants
Fibroblast Growth Factor 2
Wounds and Injuries
Injections
Scaffolds (biology)
Brain Fornix
Collagen
Grafts
Needles
Neurons
Corpus Striatum
Gels
Oligodendroglia
Graft Survival
Tissue
Cell- and Tissue-Based Therapy

Keywords

  • Extracellular matrix
  • Fibronectin
  • Neural progenitor cells
  • Stem cells
  • Tissue engineering
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Tate, M. C., Shear, D. A., Hoffman, S. W., Stein, D. G., Archer, D. R., & LaPlaca, M. C. (2002). Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain. Cell Transplantation, 11(3), 283-295.
Tate, M. C. ; Shear, D. A. ; Hoffman, S. W. ; Stein, D. G. ; Archer, D. R. ; LaPlaca, M. C. / Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain. In: Cell Transplantation. 2002 ; Vol. 11, No. 3. pp. 283-295.
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Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain. / Tate, M. C.; Shear, D. A.; Hoffman, S. W.; Stein, D. G.; Archer, D. R.; LaPlaca, M. C.

In: Cell Transplantation, Vol. 11, No. 3, 02.07.2002, p. 283-295.

Research output: Contribution to journalArticle

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T1 - Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain

AU - Tate, M. C.

AU - Shear, D. A.

AU - Hoffman, S. W.

AU - Stein, D. G.

AU - Archer, D. R.

AU - LaPlaca, M. C.

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N2 - Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons, astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (105 cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p lt; 0.01). At the longer survival times (3 weeks-3 months), 63-76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p lt; 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.

AB - Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons, astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (105 cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p lt; 0.01). At the longer survival times (3 weeks-3 months), 63-76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p lt; 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.

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