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

Therapeutic strategies using exogenous and endogenous neural stem cells (NSCs). Schematic drawing of a model for the therapeutic use of exogenous (left) and endogenous (right) NSCs. Exogenous NSCs derived from pluripotent stem cells including embryonic stem cells (ESCs) and induced-pluripotent stem cells (iPSCs) are transplanted into the damaged brain, and differentiate into mature neurons to replace damaged ones. Endogenous NSCs that reside in the subventricular zone of the adult brain continuously generate neurons, which migrate into the damaged area, where they replace damaged neurons.
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f1-genes-02-00107: Therapeutic strategies using exogenous and endogenous neural stem cells (NSCs). Schematic drawing of a model for the therapeutic use of exogenous (left) and endogenous (right) NSCs. Exogenous NSCs derived from pluripotent stem cells including embryonic stem cells (ESCs) and induced-pluripotent stem cells (iPSCs) are transplanted into the damaged brain, and differentiate into mature neurons to replace damaged ones. Endogenous NSCs that reside in the subventricular zone of the adult brain continuously generate neurons, which migrate into the damaged area, where they replace damaged neurons.

Mentions: In mammalian brain development, neural stem cells (NSCs) produce neural cells, including various types of neurons and glia. NSCs are defined as being multipotent with the capacity for self-renewal. With recent technological developments, NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells (ESCs) and induced-pluripotent stem cells (iPSCs) [1–5]. The results of animal studies [6–11] support the possibility that the transplantation of these exogenous NSCs and their progeny will be a powerful strategy for regenerating nervous system tissues damaged by disease or trauma, for which no conventional treatment is available (Figure 1, left). Before this technology can be applied to patients, however, the following problems need to be resolved. First, allotransplantation provokes immunological responses to grafted donor cells, which need to be continuously suppressed. Second, pluripotent stem cells have the potential to generate tumors [10–12]. We previously established a method for isolating neural stem cells or their progenies labeled with cell-type-specific fluorescent reporters [13–15], which decreased the tumorigenicity of the transplanted cells in rats [16]. However, considering the long lifespan of humans compared with other animals, the tumorigenic risk from stem-cell transplantation should be carefully evaluated [17], particularly because, given the limited size of the intracranial cavity, a space-occupying tumor could be fatal. It was recently reported that neurons could be generated from fibroblasts by transdifferentiation without passing through the pluripotent state, which could be an efficient procedure for avoiding tumorigenic risk in cell-transplantation therapy [18]. Third, the transplantation procedure itself might injure the complicated neuronal circuitry, affecting neurological function. Furthermore, a fundamental ethical problem lies in the therapeutic use of ESCs, which are derived from blastocysts. Thus, there are serious problems associated with regenerative medicine using cell-transplantation therapy that need to be overcome before its clinical application.


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

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

Therapeutic strategies using exogenous and endogenous neural stem cells (NSCs). Schematic drawing of a model for the therapeutic use of exogenous (left) and endogenous (right) NSCs. Exogenous NSCs derived from pluripotent stem cells including embryonic stem cells (ESCs) and induced-pluripotent stem cells (iPSCs) are transplanted into the damaged brain, and differentiate into mature neurons to replace damaged ones. Endogenous NSCs that reside in the subventricular zone of the adult brain continuously generate neurons, which migrate into the damaged area, where they replace damaged neurons.
© Copyright Policy
Related In: Results  -  Collection

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

f1-genes-02-00107: Therapeutic strategies using exogenous and endogenous neural stem cells (NSCs). Schematic drawing of a model for the therapeutic use of exogenous (left) and endogenous (right) NSCs. Exogenous NSCs derived from pluripotent stem cells including embryonic stem cells (ESCs) and induced-pluripotent stem cells (iPSCs) are transplanted into the damaged brain, and differentiate into mature neurons to replace damaged ones. Endogenous NSCs that reside in the subventricular zone of the adult brain continuously generate neurons, which migrate into the damaged area, where they replace damaged neurons.
Mentions: In mammalian brain development, neural stem cells (NSCs) produce neural cells, including various types of neurons and glia. NSCs are defined as being multipotent with the capacity for self-renewal. With recent technological developments, NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells (ESCs) and induced-pluripotent stem cells (iPSCs) [1–5]. The results of animal studies [6–11] support the possibility that the transplantation of these exogenous NSCs and their progeny will be a powerful strategy for regenerating nervous system tissues damaged by disease or trauma, for which no conventional treatment is available (Figure 1, left). Before this technology can be applied to patients, however, the following problems need to be resolved. First, allotransplantation provokes immunological responses to grafted donor cells, which need to be continuously suppressed. Second, pluripotent stem cells have the potential to generate tumors [10–12]. We previously established a method for isolating neural stem cells or their progenies labeled with cell-type-specific fluorescent reporters [13–15], which decreased the tumorigenicity of the transplanted cells in rats [16]. However, considering the long lifespan of humans compared with other animals, the tumorigenic risk from stem-cell transplantation should be carefully evaluated [17], particularly because, given the limited size of the intracranial cavity, a space-occupying tumor could be fatal. It was recently reported that neurons could be generated from fibroblasts by transdifferentiation without passing through the pluripotent state, which could be an efficient procedure for avoiding tumorigenic risk in cell-transplantation therapy [18]. Third, the transplantation procedure itself might injure the complicated neuronal circuitry, affecting neurological function. Furthermore, a fundamental ethical problem lies in the therapeutic use of ESCs, which are derived from blastocysts. Thus, there are serious problems associated with regenerative medicine using cell-transplantation therapy that need to be overcome before its clinical application.

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