Development of stem cell-based therapies for Parkinson's disease

Zhu, Bangfu; Caldwell, Maeve A.; Song, Bing

doi:10.3109/00207454.2016.1148034

Cited by 23 publications

(12 citation statements)

References 66 publications

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“…Incomplete differentiation of ESC is a major challenge for the development of an effective PD therapy and the risk of tumorigenesis may prevent the applications of ESC [ 287 ]. Induced pluripotent stem cells (iPSCs) are better sources for PD as these can be derived from the patients, thus eliminating the risk of immune rejection and the requirement of immunosuppressive therapy [ 293 ]. Unlike ESCs, iPSCs are not hindered by ethical issues [ 294 ].…”

Section: Future Directions: Search For Biomarkers and Neuroprotectmentioning

confidence: 99%

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

Sarkar

Raymick

Imam

2016

IJMS

159

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Parkinsonism is a progressive motor disease that affects 1.5 million Americans and is the second most common neurodegenerative disease after Alzheimer’s. Typical neuropathological features of Parkinson’s disease (PD) include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway) and depositions of cytoplasmic fibrillary inclusions (Lewy bodies) which contain ubiquitin and α-synuclein. The cardinal motor signs of PD are tremors, rigidity, slow movement (bradykinesia), poor balance, and difficulty in walking (Parkinsonian gait). In addition to motor symptoms, non-motor symptoms that include autonomic and psychiatric as well as cognitive impairments are pressing issues that need to be addressed. Several different mechanisms play an important role in generation of Lewy bodies; endoplasmic reticulum (ER) stress induced unfolded proteins, neuroinflammation and eventual loss of dopaminergic neurons in the substantia nigra of mid brain in PD. Moreover, these diverse processes that result in PD make modeling of the disease and evaluation of therapeutics against this devastating disease difficult. Here, we will discuss diverse mechanisms that are involved in PD, neuroprotective and therapeutic strategies currently in clinical trial or in preclinical stages, and impart views about strategies that are promising to mitigate PD pathology.

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Section: Future Directions: Search For Biomarkers and Neuroprotectmentioning

confidence: 99%

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

Sarkar

Raymick

Imam

2016

IJMS

159

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“…A bunch of studies reported the generation of dopaminergic neurons from NSCs (Ding et al 2016;Lee et al 2016a, b). Due to the fact that degradation of dopaminergic neurons plays key roles in the pathology of Parkinson's disease (PD), development of stem cell-based therapy is one of the most promising way in the treatment of PD (Zhu et al 2016). PD is a disorder of the central nervous system that mainly affects the motor system (Keranen et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model

Tang

et al. 2017

Cytotechnology

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Parkinson's disease (PD) is one of the most common neural degenerative disease, affecting millions of people globally. Great progress has been made in the PD treatment, and one of the most promising one is the stem cell-based therapy. Thus, studies on the differentiation of neural stem cells (NSCs) are important to the advancement in PD therapy. In this study, we used the rat NSCs to elucidate the role of Lithium in the proliferation and differentiation of NSCs by immunostaining against Ki67 and BrdU analysis as well as immunostaining against specific neuronal markers. We concluded that lithium chloride (LiCl) treatment could enhance the proliferation in NSCs and promote the dopaminergic neuronal differentiation of NSCs in vitro. This process was potentially mediated by Wnt signaling pathway. Using the 6-OHDA-induced PD models, we provided evidence to show that LiCl had the capacity to enhance the proliferation in NSCs and differentiation towards dopaminergic neurons in vivo. The beneficial effect of LiCl treatment was further validated by the fact that the motor function as well as learning and memory was improved in the PD models through Rotarod test and Morris water maze analysis. The learning and memory improvement was further supported by the increase in dendrite spine density in PD models receiving LiCl-treated NSCs. Through this study, we concluded that Lithium plays an important role in promoting NSCs' neuronal differentiation in vitro and improving the symptoms of PD models in vivo. It is of great significance that this work showed the potential application of Lithium in the PD therapy in the future.

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“…Prior to transplantation, three fundamental aspects must be addressed: the identification of a transplantable stage during DA neuron differentiation, in vivo DA neuronal survival, and functional assessment [10]. Currently, efficient DA neuron generation has been produced using FP-based methods [8,12,13,15,21,[29][30][31]. Different stages of DA cells have been examined individually in vivo and different conclusions have been reached [12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease

Qiu

Liao

Chen

et al. 2017

Stem Cells Translational Medicine

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Recent reports have indicated human embryonic stem cells‐derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplantation in PD therapy. Here, we transplanted three types of mDA cells, DA progenitors (differentiated in vitro for 16 days [D16]), immature DA neurons (D25), and DA neurons (D35), into PD mice and found that all three types of cells showed high viability and strong neuronal differentiation in vivo. Both D25 and D35 cells showed neuronal maturation and differentiation toward TH+ cells and, accordingly, satisfactory behavioral functional recovery. However, transplanted D16 cells were less capable of producing functional recovery. These findings provide a valuable guideline for standardizing the differentiation stage of the transplantable cells used in clinical cell therapy for PD. Stem Cells Translational Medicine 2017;6:1803–1814

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Development of stem cell-based therapies for Parkinson's disease

Cited by 23 publications

References 66 publications

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model

Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease

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