Limits...
Prospects and limitations of using endogenous neural stem cells for brain regeneration.

Kaneko N, Kako E, Sawamoto K - Genes (Basel) (2011)

Bottom Line: Recent studies have revealed that NSCs also reside in the adult brain.The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems.Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental and Regenerative Biology, Institute of Molecular Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan. naokoka@med.nagoya-cu.ac.jp.

ABSTRACT
Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

No MeSH data available.


Related in: MedlinePlus

Endogenous NSC-derived neuronal regeneration. (a) Schematic drawing of the experimental procedure. The pxCANCre plasmid was injected into the lateral ventricle 5 days before MCAO, then the fate of GFP-labeled new neurons generated in the SVZ was detected 90 days after MCAO; (b) Confocal 3D reconstruction image of a GFP (green)-labeled cell expressing the mature neuronal marker, NeuN (red). Ninety days after MCAO, 29% of the SVZ-derived GFP-positive cells around the infarcted area expressed NeuN, a specific marker for mature neurons. Scale bar: 20 μm; (c) A GFP-positive cell exhibiting a neuronal morphology. Scale bar: 20 μm; (d) An electron micrograph showing a GFP-positive axon (asterisk) containing presynaptic vesicles. A higher-magnification view of the region of the boxed area (d') shows the postsynaptic density (arrowheads). Scale bar: 0.5 μm.
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f6-genes-02-00107: Endogenous NSC-derived neuronal regeneration. (a) Schematic drawing of the experimental procedure. The pxCANCre plasmid was injected into the lateral ventricle 5 days before MCAO, then the fate of GFP-labeled new neurons generated in the SVZ was detected 90 days after MCAO; (b) Confocal 3D reconstruction image of a GFP (green)-labeled cell expressing the mature neuronal marker, NeuN (red). Ninety days after MCAO, 29% of the SVZ-derived GFP-positive cells around the infarcted area expressed NeuN, a specific marker for mature neurons. Scale bar: 20 μm; (c) A GFP-positive cell exhibiting a neuronal morphology. Scale bar: 20 μm; (d) An electron micrograph showing a GFP-positive axon (asterisk) containing presynaptic vesicles. A higher-magnification view of the region of the boxed area (d') shows the postsynaptic density (arrowheads). Scale bar: 0.5 μm.

Mentions: One of the pioneer studies of insult-induced neurogenesis showed that transient global ischemia causing the death of pyramidal neurons in the CA1 region in the hippocampus of the adult gerbil activates the proliferation of NSCs in the SGZ, increasing the number of new granule neurons in the GCL; however, the lost CA1 neurons are never replaced [96]. Another study using an adult rat model of transient global ischemia showed that NSCs/progenitors in the caudal extension of the SVZ close to the hippocampus migrate and regenerate CA1 pyramidal neurons there [97]. In addition, after focal ischemia induced by middle cerebral artery occlusion (MCAO), the most common model for ischemic stroke that causes infarction of the lateral striatum and adjacent neocortex, a small number of striatal projection neurons are regenerated [98]. That study showed that, within a week after the lesion, NSCs and progenitor cells in the SVZ begin to proliferate, and new neurons with a migratory morphology and newly generated mature neurons appear at the boundary of the damaged area in the striatum (Figure 5), but the origin of these cells was uncertain. Using viral infection-mediated cell-specific introduction of GFAP expression, we showed that these neurons are generated by GFAP-expressing NSCs in the SVZ and migrate radially into the damaged striatum, where they differentiate into mature neurons [99] (Figure 6). Thus, NSCs in the SVZ provide new neurons with a remarkable migration capacity, which may compensate for neurons lost to insult, and help regenerate the neuronal circuitry. These findings further imply that the SVZ could be an important therapeutic target for various pathological conditions.


Prospects and limitations of using endogenous neural stem cells for brain regeneration.

Kaneko N, Kako E, Sawamoto K - Genes (Basel) (2011)

Endogenous NSC-derived neuronal regeneration. (a) Schematic drawing of the experimental procedure. The pxCANCre plasmid was injected into the lateral ventricle 5 days before MCAO, then the fate of GFP-labeled new neurons generated in the SVZ was detected 90 days after MCAO; (b) Confocal 3D reconstruction image of a GFP (green)-labeled cell expressing the mature neuronal marker, NeuN (red). Ninety days after MCAO, 29% of the SVZ-derived GFP-positive cells around the infarcted area expressed NeuN, a specific marker for mature neurons. Scale bar: 20 μm; (c) A GFP-positive cell exhibiting a neuronal morphology. Scale bar: 20 μm; (d) An electron micrograph showing a GFP-positive axon (asterisk) containing presynaptic vesicles. A higher-magnification view of the region of the boxed area (d') shows the postsynaptic density (arrowheads). Scale bar: 0.5 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924842&req=5

f6-genes-02-00107: Endogenous NSC-derived neuronal regeneration. (a) Schematic drawing of the experimental procedure. The pxCANCre plasmid was injected into the lateral ventricle 5 days before MCAO, then the fate of GFP-labeled new neurons generated in the SVZ was detected 90 days after MCAO; (b) Confocal 3D reconstruction image of a GFP (green)-labeled cell expressing the mature neuronal marker, NeuN (red). Ninety days after MCAO, 29% of the SVZ-derived GFP-positive cells around the infarcted area expressed NeuN, a specific marker for mature neurons. Scale bar: 20 μm; (c) A GFP-positive cell exhibiting a neuronal morphology. Scale bar: 20 μm; (d) An electron micrograph showing a GFP-positive axon (asterisk) containing presynaptic vesicles. A higher-magnification view of the region of the boxed area (d') shows the postsynaptic density (arrowheads). Scale bar: 0.5 μm.
Mentions: One of the pioneer studies of insult-induced neurogenesis showed that transient global ischemia causing the death of pyramidal neurons in the CA1 region in the hippocampus of the adult gerbil activates the proliferation of NSCs in the SGZ, increasing the number of new granule neurons in the GCL; however, the lost CA1 neurons are never replaced [96]. Another study using an adult rat model of transient global ischemia showed that NSCs/progenitors in the caudal extension of the SVZ close to the hippocampus migrate and regenerate CA1 pyramidal neurons there [97]. In addition, after focal ischemia induced by middle cerebral artery occlusion (MCAO), the most common model for ischemic stroke that causes infarction of the lateral striatum and adjacent neocortex, a small number of striatal projection neurons are regenerated [98]. That study showed that, within a week after the lesion, NSCs and progenitor cells in the SVZ begin to proliferate, and new neurons with a migratory morphology and newly generated mature neurons appear at the boundary of the damaged area in the striatum (Figure 5), but the origin of these cells was uncertain. Using viral infection-mediated cell-specific introduction of GFAP expression, we showed that these neurons are generated by GFAP-expressing NSCs in the SVZ and migrate radially into the damaged striatum, where they differentiate into mature neurons [99] (Figure 6). Thus, NSCs in the SVZ provide new neurons with a remarkable migration capacity, which may compensate for neurons lost to insult, and help regenerate the neuronal circuitry. These findings further imply that the SVZ could be an important therapeutic target for various pathological conditions.

Bottom Line: Recent studies have revealed that NSCs also reside in the adult brain.The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems.Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental and Regenerative Biology, Institute of Molecular Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan. naokoka@med.nagoya-cu.ac.jp.

ABSTRACT
Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

No MeSH data available.


Related in: MedlinePlus