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Transplanted Neural Progenitor Cells from Distinct Sources Migrate Differentially in an Organotypic Model of Brain Injury.

Ngalula KP, Cramer N, Schell MJ, Juliano SL - Front Neurol (2015)

Bottom Line: NPCs derived from the GE tended to be immunoreactive for GABAergic markers while those derived from the neocortex were more strongly immunoreactive for other neuronal markers such as MAP2, TUJ1, or Milli-Mark.Cells transplanted in vitro acquired the electrophysiological characteristics of neurons, including action potential generation and reception of spontaneous synaptic activity.This suggests that transplanted cells differentiate into neurons capable of functionally integrating with the host tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences , Bethesda, MD , USA.

ABSTRACT
Brain injury is a major cause of long-term disability. The possibility exists for exogenously derived neural progenitor cells to repair damage resulting from brain injury, although more information is needed to successfully implement this promising therapy. To test the ability of neural progenitor cells (NPCs) obtained from rats to repair damaged neocortex, we transplanted neural progenitor cell suspensions into normal and injured slice cultures of the neocortex acquired from rats on postnatal day 0-3. Donor cells from E16 embryos were obtained from either the neocortex, including the ventricular zone (VZ) for excitatory cells, ganglionic eminence (GE) for inhibitory cells or a mixed population of the two. Cells were injected into the ventricular/subventricular zone (VZ/SVZ) or directly into the wounded region. Transplanted cells migrated throughout the cortical plate with GE and mixed population donor cells predominately targeting the upper cortical layers, while neocortically derived NPCs from the VZ/SVZ migrated less extensively. In the injured neocortex, transplanted cells moved predominantly into the wounded area. NPCs derived from the GE tended to be immunoreactive for GABAergic markers while those derived from the neocortex were more strongly immunoreactive for other neuronal markers such as MAP2, TUJ1, or Milli-Mark. Cells transplanted in vitro acquired the electrophysiological characteristics of neurons, including action potential generation and reception of spontaneous synaptic activity. This suggests that transplanted cells differentiate into neurons capable of functionally integrating with the host tissue. Together, our data suggest that transplantation of neural progenitor cells holds great potential as an emerging therapeutic intervention for restoring function lost to brain damage.

No MeSH data available.


Related in: MedlinePlus

Transplanted cell distribution in injured cultures. (A) shows examples of transfected GFP cell entering or in the injured area. An arrowhead points to a cell seeming to extend processes within the injured area. (B) is a graph of the distribution of CMDiI labeled cells transplanted into the SVZ of an injured culture that migrated into both injured and the non-injured regions of host slice. Significantly more cells migrated into the injured region (#p < 0.001) compared to the areas of no injury. Fewer neocortical cells reached the injured area compared to GE and mixed (*p < 0.05) cell populations. More of the neocortically derived cells remained in the IZ compared with the other two populations (*p < 0.05). (Two-way ANOVA followed by a post hoc pairwise comparison, Holm–Sidak, error bars = SEM). (C,D) Cells transplanted in the injury remained in place and did not show any migration. (D) is a higher powered image of the boxed in region in B. [Scale bar (A) = 100 μm; (C) = 500 μm; (D) = 20 μm]. IZ, intermediate zone; GE, cells derived from the ganglionic eminence; Ctx, cells derived from the embryonic neocortex; Mix, cells derived from a mixed population of GE and neocortically derived cells.
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Figure 4: Transplanted cell distribution in injured cultures. (A) shows examples of transfected GFP cell entering or in the injured area. An arrowhead points to a cell seeming to extend processes within the injured area. (B) is a graph of the distribution of CMDiI labeled cells transplanted into the SVZ of an injured culture that migrated into both injured and the non-injured regions of host slice. Significantly more cells migrated into the injured region (#p < 0.001) compared to the areas of no injury. Fewer neocortical cells reached the injured area compared to GE and mixed (*p < 0.05) cell populations. More of the neocortically derived cells remained in the IZ compared with the other two populations (*p < 0.05). (Two-way ANOVA followed by a post hoc pairwise comparison, Holm–Sidak, error bars = SEM). (C,D) Cells transplanted in the injury remained in place and did not show any migration. (D) is a higher powered image of the boxed in region in B. [Scale bar (A) = 100 μm; (C) = 500 μm; (D) = 20 μm]. IZ, intermediate zone; GE, cells derived from the ganglionic eminence; Ctx, cells derived from the embryonic neocortex; Mix, cells derived from a mixed population of GE and neocortically derived cells.

Mentions: To study the effect of an injury on the ability of NPCs to migrate into and populate host cortex, mechanical damage was made through the thickness of the neocortex in organotypic cultures; cells were transplanted into the VZ/SVZ as shown in Figure 1A. Transplants of all cell types into the VZ/SVZ demonstrated a targeted migration toward the lesioned zone (Figure 4A). Migrating cells also populated the area of the non-lesioned neocortex, but to a lesser extent. Cells derived from the neocortex were less efficient in migration compared to GE-derived and the mixed cell population in that more cells tended to remain in the IZ and distribute throughout the host slice (Table 2; Figure 4B). When cells were transplanted directly into the lesioned zone, they remained in that region, showing little signs of migration or moving away from the lesion site (Figures 4C,D). This was true for all transplanted cell types (derived from the neocortex alone, from the GE alone, or the mixed cell population), which all remained in the lesion.


Transplanted Neural Progenitor Cells from Distinct Sources Migrate Differentially in an Organotypic Model of Brain Injury.

Ngalula KP, Cramer N, Schell MJ, Juliano SL - Front Neurol (2015)

Transplanted cell distribution in injured cultures. (A) shows examples of transfected GFP cell entering or in the injured area. An arrowhead points to a cell seeming to extend processes within the injured area. (B) is a graph of the distribution of CMDiI labeled cells transplanted into the SVZ of an injured culture that migrated into both injured and the non-injured regions of host slice. Significantly more cells migrated into the injured region (#p < 0.001) compared to the areas of no injury. Fewer neocortical cells reached the injured area compared to GE and mixed (*p < 0.05) cell populations. More of the neocortically derived cells remained in the IZ compared with the other two populations (*p < 0.05). (Two-way ANOVA followed by a post hoc pairwise comparison, Holm–Sidak, error bars = SEM). (C,D) Cells transplanted in the injury remained in place and did not show any migration. (D) is a higher powered image of the boxed in region in B. [Scale bar (A) = 100 μm; (C) = 500 μm; (D) = 20 μm]. IZ, intermediate zone; GE, cells derived from the ganglionic eminence; Ctx, cells derived from the embryonic neocortex; Mix, cells derived from a mixed population of GE and neocortically derived cells.
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Related In: Results  -  Collection

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Figure 4: Transplanted cell distribution in injured cultures. (A) shows examples of transfected GFP cell entering or in the injured area. An arrowhead points to a cell seeming to extend processes within the injured area. (B) is a graph of the distribution of CMDiI labeled cells transplanted into the SVZ of an injured culture that migrated into both injured and the non-injured regions of host slice. Significantly more cells migrated into the injured region (#p < 0.001) compared to the areas of no injury. Fewer neocortical cells reached the injured area compared to GE and mixed (*p < 0.05) cell populations. More of the neocortically derived cells remained in the IZ compared with the other two populations (*p < 0.05). (Two-way ANOVA followed by a post hoc pairwise comparison, Holm–Sidak, error bars = SEM). (C,D) Cells transplanted in the injury remained in place and did not show any migration. (D) is a higher powered image of the boxed in region in B. [Scale bar (A) = 100 μm; (C) = 500 μm; (D) = 20 μm]. IZ, intermediate zone; GE, cells derived from the ganglionic eminence; Ctx, cells derived from the embryonic neocortex; Mix, cells derived from a mixed population of GE and neocortically derived cells.
Mentions: To study the effect of an injury on the ability of NPCs to migrate into and populate host cortex, mechanical damage was made through the thickness of the neocortex in organotypic cultures; cells were transplanted into the VZ/SVZ as shown in Figure 1A. Transplants of all cell types into the VZ/SVZ demonstrated a targeted migration toward the lesioned zone (Figure 4A). Migrating cells also populated the area of the non-lesioned neocortex, but to a lesser extent. Cells derived from the neocortex were less efficient in migration compared to GE-derived and the mixed cell population in that more cells tended to remain in the IZ and distribute throughout the host slice (Table 2; Figure 4B). When cells were transplanted directly into the lesioned zone, they remained in that region, showing little signs of migration or moving away from the lesion site (Figures 4C,D). This was true for all transplanted cell types (derived from the neocortex alone, from the GE alone, or the mixed cell population), which all remained in the lesion.

Bottom Line: NPCs derived from the GE tended to be immunoreactive for GABAergic markers while those derived from the neocortex were more strongly immunoreactive for other neuronal markers such as MAP2, TUJ1, or Milli-Mark.Cells transplanted in vitro acquired the electrophysiological characteristics of neurons, including action potential generation and reception of spontaneous synaptic activity.This suggests that transplanted cells differentiate into neurons capable of functionally integrating with the host tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences , Bethesda, MD , USA.

ABSTRACT
Brain injury is a major cause of long-term disability. The possibility exists for exogenously derived neural progenitor cells to repair damage resulting from brain injury, although more information is needed to successfully implement this promising therapy. To test the ability of neural progenitor cells (NPCs) obtained from rats to repair damaged neocortex, we transplanted neural progenitor cell suspensions into normal and injured slice cultures of the neocortex acquired from rats on postnatal day 0-3. Donor cells from E16 embryos were obtained from either the neocortex, including the ventricular zone (VZ) for excitatory cells, ganglionic eminence (GE) for inhibitory cells or a mixed population of the two. Cells were injected into the ventricular/subventricular zone (VZ/SVZ) or directly into the wounded region. Transplanted cells migrated throughout the cortical plate with GE and mixed population donor cells predominately targeting the upper cortical layers, while neocortically derived NPCs from the VZ/SVZ migrated less extensively. In the injured neocortex, transplanted cells moved predominantly into the wounded area. NPCs derived from the GE tended to be immunoreactive for GABAergic markers while those derived from the neocortex were more strongly immunoreactive for other neuronal markers such as MAP2, TUJ1, or Milli-Mark. Cells transplanted in vitro acquired the electrophysiological characteristics of neurons, including action potential generation and reception of spontaneous synaptic activity. This suggests that transplanted cells differentiate into neurons capable of functionally integrating with the host tissue. Together, our data suggest that transplantation of neural progenitor cells holds great potential as an emerging therapeutic intervention for restoring function lost to brain damage.

No MeSH data available.


Related in: MedlinePlus