Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury.
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Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury. / Xu, Jinchong; Bernreuther, Christian; Cui, Yifang; Jakovcevski, Igor; Hargus, Gunnar; Xiao, Meifang; Schachner, Melitta.
In: J NEUROTRAUM, Vol. 28, No. 9, 9, 2011, p. 1921-1937.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury.
AU - Xu, Jinchong
AU - Bernreuther, Christian
AU - Cui, Yifang
AU - Jakovcevski, Igor
AU - Hargus, Gunnar
AU - Xiao, Meifang
AU - Schachner, Melitta
PY - 2011
Y1 - 2011
N2 - A major obstacle for the transplantation of neural stem cells (NSCs) into the lesioned spinal cord is their predominant astrocytic differentiation after transplantation. We took advantage of this predominant astrocytic differentiation of NSCs and expressed the paradigmatic beneficial neural cell adhesion molecule L1 in radial glial cells and reactive and nonreactive astrocytes as novel cellular vehicles to express L1 under the control of the promoter for the human glial fibrillary acidic protein (GFAP-L1 NSCs). Behavioral analysis and electrophysiological H-reflex recordings revealed that mice transplanted with GFAP-L1 NSCs showed enhanced locomotor recovery in comparison to mice injected with wild type (WT) NSCs or control mice injected with phosphate-buffered saline (PBS). This functional recovery was further accelerated in mice transplanted with L1-expressing radial glial cells that had been immunoisolated from GFAP-L1 NSCs (GFAP-L1-i cells). Morphological analysis revealed that mice grafted with GFAP-L1 NSCs exhibited increased neuronal differentiation and migration of transplanted cells, as well as increased soma size and cholinergic synaptic coverage of host motoneurons and increased numbers of endogenous catecholaminergic nerve fibers caudal to the lesion site. These findings show that L1-expressing astrocytes and radial glial cells isolated from GFAP-L1 NSC cultures represent a novel strategy for improving functional recovery after spinal cord injury, encouraging the use of the human GFAP promoter to target beneficial transgene expression in transplanted stem cells.
AB - A major obstacle for the transplantation of neural stem cells (NSCs) into the lesioned spinal cord is their predominant astrocytic differentiation after transplantation. We took advantage of this predominant astrocytic differentiation of NSCs and expressed the paradigmatic beneficial neural cell adhesion molecule L1 in radial glial cells and reactive and nonreactive astrocytes as novel cellular vehicles to express L1 under the control of the promoter for the human glial fibrillary acidic protein (GFAP-L1 NSCs). Behavioral analysis and electrophysiological H-reflex recordings revealed that mice transplanted with GFAP-L1 NSCs showed enhanced locomotor recovery in comparison to mice injected with wild type (WT) NSCs or control mice injected with phosphate-buffered saline (PBS). This functional recovery was further accelerated in mice transplanted with L1-expressing radial glial cells that had been immunoisolated from GFAP-L1 NSCs (GFAP-L1-i cells). Morphological analysis revealed that mice grafted with GFAP-L1 NSCs exhibited increased neuronal differentiation and migration of transplanted cells, as well as increased soma size and cholinergic synaptic coverage of host motoneurons and increased numbers of endogenous catecholaminergic nerve fibers caudal to the lesion site. These findings show that L1-expressing astrocytes and radial glial cells isolated from GFAP-L1 NSC cultures represent a novel strategy for improving functional recovery after spinal cord injury, encouraging the use of the human GFAP promoter to target beneficial transgene expression in transplanted stem cells.
KW - Animals
KW - Female
KW - Mice
KW - Cell Movement
KW - Cell Proliferation
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Gliosis/metabolism
KW - Motor Activity/physiology
KW - Neural Stem Cells/metabolism/transplantation
KW - Neurogenesis/physiology
KW - Neuroglia/metabolism/transplantation
KW - Recovery of Function/physiology
KW - Spinal Cord Injuries/metabolism/physiopathology/therapy
KW - Animals
KW - Female
KW - Mice
KW - Cell Movement
KW - Cell Proliferation
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Gliosis/metabolism
KW - Motor Activity/physiology
KW - Neural Stem Cells/metabolism/transplantation
KW - Neurogenesis/physiology
KW - Neuroglia/metabolism/transplantation
KW - Recovery of Function/physiology
KW - Spinal Cord Injuries/metabolism/physiopathology/therapy
M3 - SCORING: Journal article
VL - 28
SP - 1921
EP - 1937
JO - J NEUROTRAUM
JF - J NEUROTRAUM
SN - 0897-7151
IS - 9
M1 - 9
ER -
