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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.


A subpopulation of transplanted cells detaches from the laminin scaffold.(A) The majority of transplanted cells survive along the laminin scaffold of the basal cistern. A subpopulation of cells with weaker green fluorescent protein (GFP) expression and no apparent capillary association appears to detach from the laminin scaffold of the basal cistern and migrate vertically into the CA3 area of the hippocampus 2 weeks after transplantation. (B) 4′,6-diamidino-2-phenylindole (DAPI). Scale bars: 50 μm. GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). DAPI: 1:500; Hoechst.
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Figure 2: A subpopulation of transplanted cells detaches from the laminin scaffold.(A) The majority of transplanted cells survive along the laminin scaffold of the basal cistern. A subpopulation of cells with weaker green fluorescent protein (GFP) expression and no apparent capillary association appears to detach from the laminin scaffold of the basal cistern and migrate vertically into the CA3 area of the hippocampus 2 weeks after transplantation. (B) 4′,6-diamidino-2-phenylindole (DAPI). Scale bars: 50 μm. GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). DAPI: 1:500; Hoechst.

Mentions: We observed a second population of transplanted dentate progenitor cells with weaker green fluorescent protein (GFP) expression, which had detached from the endogenous laminin scaffold and migrated into the interstitial space of the hippocampal formation (Figure 2A, B). Since we did not observe interstitial cells in the transplant core, it is possible that neural progenitor cells first need to attach to laminin after transplantation in order to survive before they follow an intrinsic program of detachment from laminin, recapitulating the in situ behavior of neural progenitor cells in the dentate subgranular vascular stem cell niche.


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

Waldau B - Neural Regen Res (2015)

A subpopulation of transplanted cells detaches from the laminin scaffold.(A) The majority of transplanted cells survive along the laminin scaffold of the basal cistern. A subpopulation of cells with weaker green fluorescent protein (GFP) expression and no apparent capillary association appears to detach from the laminin scaffold of the basal cistern and migrate vertically into the CA3 area of the hippocampus 2 weeks after transplantation. (B) 4′,6-diamidino-2-phenylindole (DAPI). Scale bars: 50 μm. GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). DAPI: 1:500; Hoechst.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590221&req=5

Figure 2: A subpopulation of transplanted cells detaches from the laminin scaffold.(A) The majority of transplanted cells survive along the laminin scaffold of the basal cistern. A subpopulation of cells with weaker green fluorescent protein (GFP) expression and no apparent capillary association appears to detach from the laminin scaffold of the basal cistern and migrate vertically into the CA3 area of the hippocampus 2 weeks after transplantation. (B) 4′,6-diamidino-2-phenylindole (DAPI). Scale bars: 50 μm. GFP: 1:2,000; polyclonal chicken; Abcam (Cambridge, MA, USA). DAPI: 1:500; Hoechst.
Mentions: We observed a second population of transplanted dentate progenitor cells with weaker green fluorescent protein (GFP) expression, which had detached from the endogenous laminin scaffold and migrated into the interstitial space of the hippocampal formation (Figure 2A, B). Since we did not observe interstitial cells in the transplant core, it is possible that neural progenitor cells first need to attach to laminin after transplantation in order to survive before they follow an intrinsic program of detachment from laminin, recapitulating the in situ behavior of neural progenitor cells in the dentate subgranular vascular stem cell niche.

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.