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Potential of Neural Stem Cell-Based Therapy for Parkinson's Disease.

Chou CH, Fan HC, Hueng DY - Parkinsons Dis (2015)

Bottom Line: Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells.With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved.As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan.

ABSTRACT
Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinson's disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

No MeSH data available.


Related in: MedlinePlus

In vitro modeling of the neurovascular environment using a novel method of coculturing human NSCs with human cerebral microvascular ECs, showing distinctive cytoarchitecture [11]. The composition of the transplant, including NSCs as well as other cellular and acellular compartments, can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). Microtubule associate protein-2 (MAP2) is a neuronal marker; glial fibrillary acid protein (GFAP) is an astrocyte marker; zonula occludens 1 (ZO1) indicates the presence of tight junction protein; diamidino-2-phenylindole (DAPI) serves as a nuclear counterstain.
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fig1: In vitro modeling of the neurovascular environment using a novel method of coculturing human NSCs with human cerebral microvascular ECs, showing distinctive cytoarchitecture [11]. The composition of the transplant, including NSCs as well as other cellular and acellular compartments, can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). Microtubule associate protein-2 (MAP2) is a neuronal marker; glial fibrillary acid protein (GFAP) is an astrocyte marker; zonula occludens 1 (ZO1) indicates the presence of tight junction protein; diamidino-2-phenylindole (DAPI) serves as a nuclear counterstain.

Mentions: Our novel model of coculturing hNSCs with human cerebral microvascular ECs (hCMECs) demonstrates a neurovascular environment, within which neuronal differentiation can be enhanced by neighboring ECs (Figure 1) [11]. The hNSC line has been shown to differentiate into cells positive for TH, and so these neurons could be guided to become DA neurons, replacing those lost in vivo. Using a novel method of modeling the NVU, unlike the Boyden chamber studies, we have shown the successful direct coculture of NSCs and hCMECs, demonstrating that direct interaction between the two cell types is possible [11, 38]. Intercellular communication is therefore possible through direct interaction of brain ECs with NSCs in vascular niches and may be essential for NSC self-renewal, proliferation, and differentiation. By understanding the interactions between NSCs and the surrounding compositions of the NVU, we can select NSCs with appropriate origins for the optimal transplant, ensuring the formation of the functional NVU and DA neuronal differentiation of NSCs. Once DA neurons are derived from transplanted NSCs and perform neurotransmission with integration into the existing nigrostriatal DA system, improvements in PD symptoms will be expected.


Potential of Neural Stem Cell-Based Therapy for Parkinson's Disease.

Chou CH, Fan HC, Hueng DY - Parkinsons Dis (2015)

In vitro modeling of the neurovascular environment using a novel method of coculturing human NSCs with human cerebral microvascular ECs, showing distinctive cytoarchitecture [11]. The composition of the transplant, including NSCs as well as other cellular and acellular compartments, can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). Microtubule associate protein-2 (MAP2) is a neuronal marker; glial fibrillary acid protein (GFAP) is an astrocyte marker; zonula occludens 1 (ZO1) indicates the presence of tight junction protein; diamidino-2-phenylindole (DAPI) serves as a nuclear counterstain.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4664819&req=5

fig1: In vitro modeling of the neurovascular environment using a novel method of coculturing human NSCs with human cerebral microvascular ECs, showing distinctive cytoarchitecture [11]. The composition of the transplant, including NSCs as well as other cellular and acellular compartments, can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). Microtubule associate protein-2 (MAP2) is a neuronal marker; glial fibrillary acid protein (GFAP) is an astrocyte marker; zonula occludens 1 (ZO1) indicates the presence of tight junction protein; diamidino-2-phenylindole (DAPI) serves as a nuclear counterstain.
Mentions: Our novel model of coculturing hNSCs with human cerebral microvascular ECs (hCMECs) demonstrates a neurovascular environment, within which neuronal differentiation can be enhanced by neighboring ECs (Figure 1) [11]. The hNSC line has been shown to differentiate into cells positive for TH, and so these neurons could be guided to become DA neurons, replacing those lost in vivo. Using a novel method of modeling the NVU, unlike the Boyden chamber studies, we have shown the successful direct coculture of NSCs and hCMECs, demonstrating that direct interaction between the two cell types is possible [11, 38]. Intercellular communication is therefore possible through direct interaction of brain ECs with NSCs in vascular niches and may be essential for NSC self-renewal, proliferation, and differentiation. By understanding the interactions between NSCs and the surrounding compositions of the NVU, we can select NSCs with appropriate origins for the optimal transplant, ensuring the formation of the functional NVU and DA neuronal differentiation of NSCs. Once DA neurons are derived from transplanted NSCs and perform neurotransmission with integration into the existing nigrostriatal DA system, improvements in PD symptoms will be expected.

Bottom Line: Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells.With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved.As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 11490, Taiwan.

ABSTRACT
Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinson's disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

No MeSH data available.


Related in: MedlinePlus