TY - JOUR
T1 - Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment
AU - Corti, S.
AU - Locatelli, F.
AU - Strazzer, S.
AU - Salani, S.
AU - Del Bo, R.
AU - Soligo, D.
AU - Bossolasco, P.
AU - Bresolin, N.
AU - Scarlato, G.
AU - Comi, G. P.
PY - 2002
Y1 - 2002
N2 - The aim of the present study is to determine whether the expansion and mobilization of circulating bone marrow (BM) stem cells by in vivo treatment with granulocyte-colony stimulating factor (G-CSF) and stem cell factor (SCF) increase the amount of BM-derived neuronal cells in mouse brain. The presence of BM-derived cells in the brain was traced by transplanting into lethally irradiated adults and newborns adult BM from transgenic mice that ubiquitously expressed enhanced green fluorescent protein (GFP). GFP+ and Y-chromosome+ donor-derived cells were present in several brain areas of all treated mice (cortical and subcortical areas, cerebellum, olfactory bulb). The presence of GFP+ cells expressing nuclear neural specific antigen (NeuN), neurofilament, and β-III tubulin in cortical forebrain and olfactory bulb (OB) was higher in G-CSF-SCF treated groups (P <0.05, analysis of variance, Fisher post hoc). We observed that overall the amount of double positive cells was higher in animals treated at birth than in adults and in OB than in forebrain areas (P <0.05). Temporal cortical areas of cytokine-treated adult animals revealed a mean threefold increase in the number of GFP+ cells expressing the nuclear neural specific antigen (211 ± 86 GFP+NeuN+/mm3 in G-CSF + SCF treated mice and 66 ± 33 GFP+NeuN+/mm3 in control animals). GFP+ cells coexpressing neuronal markers contain only one nucleus and have a DNA index (a measure of DNA ploidy) identical to that of surrounding neurons, thus excluding donor cell fusion with endogenous cells as a relevant phenomenon under these experimental conditions. Our results indicate that G-CSF and SCF administration modulates the availability of GFP+ cells in the brain and enhances their capacity to acquire neuronal characteristics. Cytokine stimulation of autologous stem cells might be seen as a new strategy for neuronal repair in neuro-degenerative diseases.
AB - The aim of the present study is to determine whether the expansion and mobilization of circulating bone marrow (BM) stem cells by in vivo treatment with granulocyte-colony stimulating factor (G-CSF) and stem cell factor (SCF) increase the amount of BM-derived neuronal cells in mouse brain. The presence of BM-derived cells in the brain was traced by transplanting into lethally irradiated adults and newborns adult BM from transgenic mice that ubiquitously expressed enhanced green fluorescent protein (GFP). GFP+ and Y-chromosome+ donor-derived cells were present in several brain areas of all treated mice (cortical and subcortical areas, cerebellum, olfactory bulb). The presence of GFP+ cells expressing nuclear neural specific antigen (NeuN), neurofilament, and β-III tubulin in cortical forebrain and olfactory bulb (OB) was higher in G-CSF-SCF treated groups (P <0.05, analysis of variance, Fisher post hoc). We observed that overall the amount of double positive cells was higher in animals treated at birth than in adults and in OB than in forebrain areas (P <0.05). Temporal cortical areas of cytokine-treated adult animals revealed a mean threefold increase in the number of GFP+ cells expressing the nuclear neural specific antigen (211 ± 86 GFP+NeuN+/mm3 in G-CSF + SCF treated mice and 66 ± 33 GFP+NeuN+/mm3 in control animals). GFP+ cells coexpressing neuronal markers contain only one nucleus and have a DNA index (a measure of DNA ploidy) identical to that of surrounding neurons, thus excluding donor cell fusion with endogenous cells as a relevant phenomenon under these experimental conditions. Our results indicate that G-CSF and SCF administration modulates the availability of GFP+ cells in the brain and enhances their capacity to acquire neuronal characteristics. Cytokine stimulation of autologous stem cells might be seen as a new strategy for neuronal repair in neuro-degenerative diseases.
KW - Bone marrow transplantation
KW - GFP
KW - Neuronal neogenesis
KW - Stem cells
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U2 - 10.1006/exnr.2002.8004
DO - 10.1006/exnr.2002.8004
M3 - Article
C2 - 12429190
AN - SCOPUS:0036434927
VL - 177
SP - 443
EP - 452
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 2
ER -