Dataset Information

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

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.

SUBMITTER: Chou CH

PROVIDER: S-EPMC4664819 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chou Chung-Hsing CH Fan Hueng-Chuen HC Hueng Dueng-Yuan DY

Parkinson's disease 20151117

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 ...[more]

PMID: 26664823

Similar Datasets

Project description:Neurons derived from human pluripotent stem cells (hPSCs) provide a valuable tool for studying human neural development and neurodegenerative diseases. The investigation of hPSC-based cell therapy, involving the differentiation of hPSCs into target cells and their transplantation into affected regions, is of particular interest. One neurodegenerative disease that is being extensively studied for hPSC-based cell therapy is Parkinson's disease (PD), the second most common among humans. Various research groups are focused on differentiating hPSCs into ventral midbrain dopaminergic (vmDA) progenitors, which have the potential to further differentiate into neurons closely resembling DA neurons found in the substantia nigra pars compacta (SNpc) after transplantation, providing a promising treatment option for PD. In vivo experiments, where hPSC-derived vmDA progenitor cells were transplanted into the striatum or SNpc of animal PD models, the transplanted cells demonstrated stable engraftment and resulted in behavioral recovery in the transplanted animals. Several differentiation protocols have been developed for this specific cell therapy. However, the lack of a reliable live-cell lineage identification method presents a significant obstacle in confirming the precise lineage of the differentiated cells intended for transplantation, as well as identifying potential contamination by non-vmDA progenitors. This deficiency increases the risk of adverse effects such as dyskinesias and tumorigenicity, highlighting the importance of addressing this issue before proceeding with transplantation. Ensuring the differentiation of hPSCs into the target cell lineage is a crucial step to guarantee precise therapeutic effects in cell therapy. To underscore the significance of lineage identification, this review focuses on the differentiation protocols of hPSC-derived vmDA progenitors developed by various research groups for PD treatment. Moreover, in vivo experimental results following transplantation were carefully analyzed. The encouraging outcomes from these experiments demonstrate the potential efficacy and safety of hPSC-derived vmDA progenitors for PD cell therapy. Additionally, the results of clinical trials involving the use of hPSC-derived vmDA progenitors for PD treatment were briefly reviewed, shedding light on the progress and challenges faced in translating this promising therapy into clinical practice.

Project description:BackgroundStem cells hold tremendous promise for regenerative medicine because they can be expanded infinitely, giving rise to large numbers of differentiated cells required for transplantation. Stem cells can be derived from fetal sources, embryonic origins (embryonic stem cells or ESCs) or reprogrammed from adult cell types (induced pluripotent stem cells or iPSCs). One unique property of stem cells is their ability to be directed towards specific cell types of clinical interest, and can mature into functional cell types in vivo. While transplantations of fetal or ESC-derived tissues are known to illicit a host immunogenic response, autologous transplantations using cell types derived from one's own iPSCs eliminate risks of tissue rejection and reduce the need for immunosuppressants. However, even with these benefits, cell therapy comes with significant hurdles that researchers are starting to overcome. In this review, we will discuss the various steps to ensure safety, efficacy and clinical practicality of cell replacement therapy in neurodegenerative diseases, in particular, Parkinson's disease.Main bodyParkinson's disease (PD) results from a loss of dopaminergic neurons from the substantia nigra and is an ideal target for cell replacement therapy. Early trials using fetal midbrain material in the late 1980s have resulted in long term benefit for some patients, but there were multiple shortcomings including the non-standardization and quality control of the transplanted fetal material, and graft-induced dyskinesia that some patients experience as a result. On the other hand, pluripotent stem cells such as ESCs and iPSCs serve as an attractive source of cells because they can be indefinitely cultured and is an unlimited source of cells. Stem cell technologies and our understanding of the developmental potential of ESCs and iPSCs have deepened in recent years and a clinical trial for iPSC-derived dopaminergic cells is currently undergoing for PD patients in Japan. In this focused review, we will first provide a historical aspect of cell therapies in PD, and then discuss the various challenges pertaining to the safety and efficacy of stem cell-based cell transplantations, and how these hurdles were eventually overcome.ConclusionWith the maturity of the iPSC technology, cell transplantation appears to be a safe and effective therapy. Grafts in non-human primates survive and remain functional for more than 2 years after transplantation, with no signs of tumorigenesis, indicating safety and efficacy of the treatment. However, immunosuppressants are still required because of the lack of "universal stem cells" that would not evoke an immune response. The results of ongoing and upcoming trials by a global consortium known as GForce-PD would be highly anticipated because the success of these trials would open up possibilities for using cell therapy for the treatment of PD and other degenerative diseases.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets