Prolonged survival and expression of neural markers by bone marrow-derived stem cells transplanted into brain lesions

BACKGROUND: Bone marrow-derived stem cell transplantation is a potentially viable therapeutic option for the treatment of neurodegenerative disease. MATERIAL/METHODS: We have isolated bone marrow stem cells by standard method. We then evaluated the survival of rats' bone marrow mononuclear cells implanted in rats' brain. The cells were extracted from rats' femurs, and marked for monitoring purposes by adenoviral transduction with Green Fluorescent Protein (GFP). Labeled cells were implanted within the area of rats' striatum lesions that were induced a month earlier employing quinolinic acid-based method. The implants were phenotyped by monitoring CD34; CD38; CD45 and CD90 expression. Bone marrow stromal cells were extracted from rats' femurs and cultivated until monolayer bone marrow stromal cells were obtained. The ability of bone marrow stromal cells to express NGF and GDNF was evaluated by RT-PCR. RESULTS: Implanted cells survived for at least one month after transplantation and dispersed from the area of injection towards corpus callosum and brain cortex. Interestingly, passaged rat bone marrow stromal cells expressed NGF and GDNF mRNA. CONCLUSIONS: The bone marrow cells could be successfully transplanted to the brain either for the purpose of trans-differentiation, or for the expression of desired growth factors(AU)

Prolonged survival and expression of neural markers by bone marrow-derived stem cells transplanted into brain lesions.

BACKGROUND: Bone marrow-derived stem cell transplantation is a potentially viable therapeutic option for the treatment of neurodegenerative disease. MATERIAL/METHODS: We have isolated bone marrow stem cells by standard method. We then evaluated the survival of rats' bone marrow mononuclear cells implanted in rats' brain. The cells were extracted from rats' femurs, and marked for monitoring purposes by adenoviral transduction with Green Fluorescent Protein (GFP). Labeled cells were implanted within the area of rats' striatum lesions that were induced a month earlier employing quinolinic acid-based method. The implants were phenotyped by monitoring CD34; CD38; CD45 and CD90 expression. Bone marrow stromal cells were extracted from rats' femurs and cultivated until monolayer bone marrow stromal cells were obtained. The ability of bone marrow stromal cells to express NGF and GDNF was evaluated by RT-PCR. RESULTS: Implanted cells survived for at least one month after transplantation and dispersed from the area of injection towards corpus callosum and brain cortex. Interestingly, passaged rat bone marrow stromal cells expressed NGF and GDNF mRNA. CONCLUSIONS: The bone marrow cells could be successfully transplanted to the brain either for the purpose of trans-differentiation, or for the expression of desired growth factors.

Motor and cognitive recovery induced by bone marrow stem cells grafted to striatum and hippocampus of impaired aged rats: functional and therapeutic considerations.

Impairments in motor coordination and cognition in normal and pathological aging are often accompanied by structural changes, that is, loss of synapses and neurons. Also, it has been shown recently that bone marrow stem cells can give origin to cells of different tissues, including neural cells. Given the therapeutic implications of increasing health and functional possibilities in the aged brain, we have tested the effects of rat femur bone marrow stem cells (rBMSCs) grafting to the striatum hippocampus of aged rats with motor or cognitive deficits, respectively. Bone marrow cells were transduced with an adenovirus driving the expression of green fluorescence protein (GFP) and other classic stains to determine their migration, engraftment, differentiation, and associated behavioral recovery. Five weeks after it, control and grafted rats were re-evaluated with the Morris Water Maze test, Passive avoidance, open-field, motor coordination, and Marshall tests and perfused. Brains were processed and analyzed for fluorescent protein expression. GFP was detected in cells with some differentiation degree into neural-like cells. Their exact phenotype is yet to be determined. A significant functional recovery was observed 6 weeks after grafting, suggesting a trophic interaction between rBMSCs and the aged/dystrophic host brain, or with the host brain progenitor cells and/or by increasing the number of functional cells at striatum or hippocampus, suggesting that the aging brain keeps its functional plasticity as well as that BMSCs are interesting candidates for cell replacement therapies in neurodegenerative disorders.

Characterization of proliferation and differentiation of EGF-responsive striatal and septal precursor cells.

The epigenetic manipulation of precursors may provide data to elucidate the potential interactions among these cells in different brain regions. However, the response to epigenetic signals is modulated by the environment in which the cells are manipulated. Therefore, data regarding the action of a particular factor must be considered in the light of a specific system. To compare septal and striatal precursors, we have tested the effect of nerve growth factor (NGF) on the proliferation and neuronal differentiation of epidermal growth factor (EGF)-responsive cells from these brain regions. Precursors were cultivated as 'neuropheres' in serum free medium (SFM) to which NGF was added. NGF did not support the proliferation of EGF-generated precursors so that no differences in the cell magnitude with respect to control cultures were observed. Differentiation of precursors in SFM plus 1% fetal bovine serum (FBS) on poly-D-lysine showed that the neuron number was increased two-fold in septal cultures treated with NGF but not in those from striatum. A quantitative evaluation of the soma surface and the number of primary neurites showed differences between both populations of precursor-generated neurons. In addition, we also observed no influence of NGF on these parameters of cellular morphology. Thus, taken together these results seem to indicate that at this developmental stage in which these populations of precursors were isolated, heterogeneities exist between them, which is probably related to their origin and/or functional roles in vivo.