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The vascular stem cell niche: roadmap for transplanted neural progenitor cells during environmental enrichment?

Waldau B - Neural Regen Res (2015)

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, UC Davis Medical Center, 4860 Y Street, ACC 3740, Sacramento 95817, CA, USA.

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One of the challenges of cell transplantation into the brain is poor graft survival... Graft survival may be affected by an immunological response of the host towards transplanted cells, shear injury to cells during transplantation or an unsuitable micro-environment for the transplanted cell type... Laminin is an important constituent of the basal membrane of brain capillaries... We also found abundant expression of laminin in the basal cistern along the apical surface of the molecular layer of the dentate gyrus (Jamal et al., 2015)... Neural progenitor cell transplantation studies have shown poor graft survival in host tissue after stereotactic injection (Waldau, 2010)... Neurosurgeons are familiar with the anatomy of these cerebrospinal fluid (CSF) cisterns to directly deliver progenitor cells during a small craniotomy... A small craniotomy may be superior to a stereotactic injection in the vicinity of blood vessels to avoid the risk of vascular injury... The escape of neural progenitor cells from the laminin scaffold of brain capillaries may also have implications for the brain tumor stem cell theory... Elevated expression of integrin α6 has been found in glioblastoma stem cells, and targeting of integrin α6 attenuates self-renewal and tumor formation (Lathia et al., 2010)... Transplantation of cancer stem cells into the vascular niche may serve as a model to study the early stages of tumor development and the interaction of the vascular stem cell niche with therapeutic agents... In conclusion, we observed that transplanted neural progenitor cells are closely associated with the vascular stem cell niche and responsive to environmental enrichment... Therefore, survival of neural progenitor cell grafts in humans may be enhanced by physical, occupational or speech therapy to increase regional brain perfusion and help promote survival of transplanted cells in desired target areas... This work was supported by the 2011 William P... Van Wagenen Award from the American Association of Neurological Surgeons (AANS) and basic institutional funding.

No MeSH data available.


Laminin is important for the initial survival of transplanted neural progenitor cells in vivo.(A) The basal cistern bordering the molecular layer of the dentate gyrus exhibits abundant expression of laminin. Transplanted neural progenitor cells seem to initially survive best on the laminin scaffold of the basal cistern 2 weeks after transplantation. Scale bar: 50 μm. (B) Transplanted neural progenitor cells appear to migrate at the same time along the laminin-rich basal membrane of capillaries into the dentate gyrus. Scale bar: 20 μm. (C) Transplanted neural progenitor cells with strong green fluorescent protein (GFP) expression are tightly associated with capillaries. Scale bar: 20 μm. Laminin: 1:400; polyclonal rabbit; Sigma Aldrich (St. Louis, MO, USA). GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). 4′,6-diamidino-2-phenylindole (DAPI): 1:500; Hoechst.
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Figure 1: Laminin is important for the initial survival of transplanted neural progenitor cells in vivo.(A) The basal cistern bordering the molecular layer of the dentate gyrus exhibits abundant expression of laminin. Transplanted neural progenitor cells seem to initially survive best on the laminin scaffold of the basal cistern 2 weeks after transplantation. Scale bar: 50 μm. (B) Transplanted neural progenitor cells appear to migrate at the same time along the laminin-rich basal membrane of capillaries into the dentate gyrus. Scale bar: 20 μm. (C) Transplanted neural progenitor cells with strong green fluorescent protein (GFP) expression are tightly associated with capillaries. Scale bar: 20 μm. Laminin: 1:400; polyclonal rabbit; Sigma Aldrich (St. Louis, MO, USA). GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). 4′,6-diamidino-2-phenylindole (DAPI): 1:500; Hoechst.

Mentions: One of the challenges of cell transplantation into the brain is poor graft survival. Graft survival may be affected by an immunological response of the host towards transplanted cells, shear injury to cells during transplantation or an unsuitable micro-environment for the transplanted cell type. Neural progenitor cells have an affinity to laminin, which is commonly used to maintain neural progenitors as monolayer cultures in vitro. The affinity of neural progenitor cells to laminin is based on the high expression of α6β1 integrin, which is required for binding of neural progenitors to endothelial cells (Hall et al., 2006; Shen et al., 2008). Mice with targeted disruption of β1 integrin have substantial layering deficits in developing neocortex (Loulier et al., 2009). Laminin is an important constituent of the basal membrane of brain capillaries. We also found abundant expression of laminin in the basal cistern along the apical surface of the molecular layer of the dentate gyrus (Jamal et al., 2015). Transplanted dentate progenitor cells did not survive in the transplant core within the dentate gyrus, but initially rather exclusively survived along the laminin scaffold of the basal cistern (Figure 1A). The laminin of the basal cistern is connected to the laminin of the capillary network of the dentate gyrus. It appeared as if transplanted dentate progenitor cells initially settled on the dense laminin scaffold of the basal cistern and then migrated into the hippocampal formation using laminin of dentate capillaries as tram tracks (Figure 1B, C). Even though we expanded neural progenitor cells on laminin-coated tissue culture flasks, which may have selected for neural progenitor cells with a strong affinity to laminin, we observed the same in vivo affinity to laminin after growing neural progenitor cells as neurospheres for 5 days before transplantation. Also, previous experiments with neural progenitor cells grown exclusively as neurospheres before transplantation showed the greatest survival of cells along the laminin-rich basal cistern adjacent to the dentate gyrus instead of in the transplant core within the parenchyma of the hippocampal formation (Waldau et al., 2010).


The vascular stem cell niche: roadmap for transplanted neural progenitor cells during environmental enrichment?

Waldau B - Neural Regen Res (2015)

Laminin is important for the initial survival of transplanted neural progenitor cells in vivo.(A) The basal cistern bordering the molecular layer of the dentate gyrus exhibits abundant expression of laminin. Transplanted neural progenitor cells seem to initially survive best on the laminin scaffold of the basal cistern 2 weeks after transplantation. Scale bar: 50 μm. (B) Transplanted neural progenitor cells appear to migrate at the same time along the laminin-rich basal membrane of capillaries into the dentate gyrus. Scale bar: 20 μm. (C) Transplanted neural progenitor cells with strong green fluorescent protein (GFP) expression are tightly associated with capillaries. Scale bar: 20 μm. Laminin: 1:400; polyclonal rabbit; Sigma Aldrich (St. Louis, MO, USA). GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). 4′,6-diamidino-2-phenylindole (DAPI): 1:500; Hoechst.
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Figure 1: Laminin is important for the initial survival of transplanted neural progenitor cells in vivo.(A) The basal cistern bordering the molecular layer of the dentate gyrus exhibits abundant expression of laminin. Transplanted neural progenitor cells seem to initially survive best on the laminin scaffold of the basal cistern 2 weeks after transplantation. Scale bar: 50 μm. (B) Transplanted neural progenitor cells appear to migrate at the same time along the laminin-rich basal membrane of capillaries into the dentate gyrus. Scale bar: 20 μm. (C) Transplanted neural progenitor cells with strong green fluorescent protein (GFP) expression are tightly associated with capillaries. Scale bar: 20 μm. Laminin: 1:400; polyclonal rabbit; Sigma Aldrich (St. Louis, MO, USA). GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). 4′,6-diamidino-2-phenylindole (DAPI): 1:500; Hoechst.
Mentions: One of the challenges of cell transplantation into the brain is poor graft survival. Graft survival may be affected by an immunological response of the host towards transplanted cells, shear injury to cells during transplantation or an unsuitable micro-environment for the transplanted cell type. Neural progenitor cells have an affinity to laminin, which is commonly used to maintain neural progenitors as monolayer cultures in vitro. The affinity of neural progenitor cells to laminin is based on the high expression of α6β1 integrin, which is required for binding of neural progenitors to endothelial cells (Hall et al., 2006; Shen et al., 2008). Mice with targeted disruption of β1 integrin have substantial layering deficits in developing neocortex (Loulier et al., 2009). Laminin is an important constituent of the basal membrane of brain capillaries. We also found abundant expression of laminin in the basal cistern along the apical surface of the molecular layer of the dentate gyrus (Jamal et al., 2015). Transplanted dentate progenitor cells did not survive in the transplant core within the dentate gyrus, but initially rather exclusively survived along the laminin scaffold of the basal cistern (Figure 1A). The laminin of the basal cistern is connected to the laminin of the capillary network of the dentate gyrus. It appeared as if transplanted dentate progenitor cells initially settled on the dense laminin scaffold of the basal cistern and then migrated into the hippocampal formation using laminin of dentate capillaries as tram tracks (Figure 1B, C). Even though we expanded neural progenitor cells on laminin-coated tissue culture flasks, which may have selected for neural progenitor cells with a strong affinity to laminin, we observed the same in vivo affinity to laminin after growing neural progenitor cells as neurospheres for 5 days before transplantation. Also, previous experiments with neural progenitor cells grown exclusively as neurospheres before transplantation showed the greatest survival of cells along the laminin-rich basal cistern adjacent to the dentate gyrus instead of in the transplant core within the parenchyma of the hippocampal formation (Waldau et al., 2010).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, UC Davis Medical Center, 4860 Y Street, ACC 3740, Sacramento 95817, CA, USA.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

One of the challenges of cell transplantation into the brain is poor graft survival... Graft survival may be affected by an immunological response of the host towards transplanted cells, shear injury to cells during transplantation or an unsuitable micro-environment for the transplanted cell type... Laminin is an important constituent of the basal membrane of brain capillaries... We also found abundant expression of laminin in the basal cistern along the apical surface of the molecular layer of the dentate gyrus (Jamal et al., 2015)... Neural progenitor cell transplantation studies have shown poor graft survival in host tissue after stereotactic injection (Waldau, 2010)... Neurosurgeons are familiar with the anatomy of these cerebrospinal fluid (CSF) cisterns to directly deliver progenitor cells during a small craniotomy... A small craniotomy may be superior to a stereotactic injection in the vicinity of blood vessels to avoid the risk of vascular injury... The escape of neural progenitor cells from the laminin scaffold of brain capillaries may also have implications for the brain tumor stem cell theory... Elevated expression of integrin α6 has been found in glioblastoma stem cells, and targeting of integrin α6 attenuates self-renewal and tumor formation (Lathia et al., 2010)... Transplantation of cancer stem cells into the vascular niche may serve as a model to study the early stages of tumor development and the interaction of the vascular stem cell niche with therapeutic agents... In conclusion, we observed that transplanted neural progenitor cells are closely associated with the vascular stem cell niche and responsive to environmental enrichment... Therefore, survival of neural progenitor cell grafts in humans may be enhanced by physical, occupational or speech therapy to increase regional brain perfusion and help promote survival of transplanted cells in desired target areas... This work was supported by the 2011 William P... Van Wagenen Award from the American Association of Neurological Surgeons (AANS) and basic institutional funding.

No MeSH data available.