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Transplantation of adult neural progenitor cells transfected with vascular endothelial growth factor rescues grafted cells in the rat brain.

Maurer MH, Thomas C, Bürgers HF, Kuschinsky W - Int. J. Biol. Sci. (2007)

Bottom Line: Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs).We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days.In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pathophysiology, University of Heidelberg, Heidelberg, Germany. maurer@physiologie.uni-heidelberg.de

ABSTRACT
Growth factors are currently evaluated as therapeutics in stroke and neurodegeneration. Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs). In the current study, we investigated whether NPCs expressing Vascular Endothelial Growth Factor VEGF-A165 are a useful vehicle for growth factor delivery after transplantation into the caudate putamen of the rat brain. We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days. Additional brain immunohistochemistry revealed increased expression of the endothelial cell marker PECAM-1 (CD31) after 24 hours, 4 day, and 11 days after transplantation. In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs. Moreover, transplantation of VEGF-expressing NPCs supports angiogenesis in the brain, which may contribute to potential brain repair.

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Immunohistochemical characterization of the cultured NPCs. We stained the cultured cells using a set of different antibodies directed against marker proteins for precursor cells (A, nestin; B, doublecortin DCX), neurons (C, tubulin ßIII, clone TuJ-1; D, neurofilament 70 kDa NF70), astrocytes (E, glial acidic fibrillary protein GFAP), oligodendrocytes (F, O4), and endothelial cells/capillaries (G, CD31). Additionally, the respective controls for the secondary fluorescent antibodies labeled with Cy3 (H) and Cy5 (I) are shown. The percentage in the upper right corner of each panel gives the percentage of cells positive for the respective marker. The NPCs are highly positive for progenitor cell markers and neuronal markers, but they do only show faint immunoreactivity for astrocytic and oligodendrocytic markers, and no immunoreactivity for CD31 as well as for the negative controls.
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Figure 1: Immunohistochemical characterization of the cultured NPCs. We stained the cultured cells using a set of different antibodies directed against marker proteins for precursor cells (A, nestin; B, doublecortin DCX), neurons (C, tubulin ßIII, clone TuJ-1; D, neurofilament 70 kDa NF70), astrocytes (E, glial acidic fibrillary protein GFAP), oligodendrocytes (F, O4), and endothelial cells/capillaries (G, CD31). Additionally, the respective controls for the secondary fluorescent antibodies labeled with Cy3 (H) and Cy5 (I) are shown. The percentage in the upper right corner of each panel gives the percentage of cells positive for the respective marker. The NPCs are highly positive for progenitor cell markers and neuronal markers, but they do only show faint immunoreactivity for astrocytic and oligodendrocytic markers, and no immunoreactivity for CD31 as well as for the negative controls.

Mentions: A prerequisite of any transplantation study is to characterize the graft previous to the transplantation. Therefore, we characterized the cultured NPCs by immunostaining for multiple cellular markers (Fig. 1). Whereas the NPC markers Nestin and Doublecortin as well as the neuronal markers Tubulin-ßIII and neurofilament 70 kDa NF70 are expressed in the graft, only faint immunoreactivity is found for astrocytic (GFAP) and oligodendrocytic (O4) markers, and no immunoreactivity for endothelial cells/capillaries (CD31).


Transplantation of adult neural progenitor cells transfected with vascular endothelial growth factor rescues grafted cells in the rat brain.

Maurer MH, Thomas C, Bürgers HF, Kuschinsky W - Int. J. Biol. Sci. (2007)

Immunohistochemical characterization of the cultured NPCs. We stained the cultured cells using a set of different antibodies directed against marker proteins for precursor cells (A, nestin; B, doublecortin DCX), neurons (C, tubulin ßIII, clone TuJ-1; D, neurofilament 70 kDa NF70), astrocytes (E, glial acidic fibrillary protein GFAP), oligodendrocytes (F, O4), and endothelial cells/capillaries (G, CD31). Additionally, the respective controls for the secondary fluorescent antibodies labeled with Cy3 (H) and Cy5 (I) are shown. The percentage in the upper right corner of each panel gives the percentage of cells positive for the respective marker. The NPCs are highly positive for progenitor cell markers and neuronal markers, but they do only show faint immunoreactivity for astrocytic and oligodendrocytic markers, and no immunoreactivity for CD31 as well as for the negative controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2140152&req=5

Figure 1: Immunohistochemical characterization of the cultured NPCs. We stained the cultured cells using a set of different antibodies directed against marker proteins for precursor cells (A, nestin; B, doublecortin DCX), neurons (C, tubulin ßIII, clone TuJ-1; D, neurofilament 70 kDa NF70), astrocytes (E, glial acidic fibrillary protein GFAP), oligodendrocytes (F, O4), and endothelial cells/capillaries (G, CD31). Additionally, the respective controls for the secondary fluorescent antibodies labeled with Cy3 (H) and Cy5 (I) are shown. The percentage in the upper right corner of each panel gives the percentage of cells positive for the respective marker. The NPCs are highly positive for progenitor cell markers and neuronal markers, but they do only show faint immunoreactivity for astrocytic and oligodendrocytic markers, and no immunoreactivity for CD31 as well as for the negative controls.
Mentions: A prerequisite of any transplantation study is to characterize the graft previous to the transplantation. Therefore, we characterized the cultured NPCs by immunostaining for multiple cellular markers (Fig. 1). Whereas the NPC markers Nestin and Doublecortin as well as the neuronal markers Tubulin-ßIII and neurofilament 70 kDa NF70 are expressed in the graft, only faint immunoreactivity is found for astrocytic (GFAP) and oligodendrocytic (O4) markers, and no immunoreactivity for endothelial cells/capillaries (CD31).

Bottom Line: Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs).We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days.In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pathophysiology, University of Heidelberg, Heidelberg, Germany. maurer@physiologie.uni-heidelberg.de

ABSTRACT
Growth factors are currently evaluated as therapeutics in stroke and neurodegeneration. Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs). In the current study, we investigated whether NPCs expressing Vascular Endothelial Growth Factor VEGF-A165 are a useful vehicle for growth factor delivery after transplantation into the caudate putamen of the rat brain. We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days. Additional brain immunohistochemistry revealed increased expression of the endothelial cell marker PECAM-1 (CD31) after 24 hours, 4 day, and 11 days after transplantation. In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs. Moreover, transplantation of VEGF-expressing NPCs supports angiogenesis in the brain, which may contribute to potential brain repair.

Show MeSH
Related in: MedlinePlus