Differentiation of transplanted bone marrow cells in the adult mouse brain.
BACKGROUND
Bone marrow transplantation is reportedly effective in preventing the progression of neurological deterioration in lysosomal storage disorders, although the mechanism underlying the therapeutic effects remains to be elucidated. Recent research on stem cell biology suggests that bone marrow cells contain nonhematopoietic stem cells, including brain precursor cells. To evaluate the contribution of bone marrow cells as carriers for cell and gene therapy of neurological disorders, we studied the fate of transplanted bone marrow cells in the adult mouse brain.


METHODS
Bone marrow cells were genetically marked with a retroviral vector containing the green fluorescence protein gene and then transplanted into irradiated mice by either systemic infusion or direct injection. To identify cell types, brain sections were stained with specific antibodies against neuronal cell markers-neuron specific enolase for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1 (Iba1) for microglia-and then examined under a confocal microscope.


RESULTS
Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but none of the other brain cell markers. Conversely, 12 weeks after direct injection, transplanted cells were stained with antibodies against GFAP, CAII, and Iba1.


CONCLUSIONS
Bone marrow contains cells capable of differentiating into oligodendrocytes, astrocytes, and microglia when exposed to the brain microenvironment. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for lysosomal disorders with neurological symptoms.
Nakano
K
K
Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Migita
M
M
Mochizuki
H
H
Shimada
T
T
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000601:surgery*; D002454:Cell Differentiation; D003342:Corpus Striatum; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D007267:Injections; D007275:Injections, Intravenous; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000473:pathology; D013238:Stereotaxic Techniques; D014161:Transduction, Genetic
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins