Development and application of neural stem cells for treating various human neurological diseases in animal models

Yi, Bo‐Rim; Kim, Seung Up; Choi, Kyung‐Chul

doi:10.5625/lar.2013.29.3.131

Cited by 24 publications

(18 citation statements)

References 68 publications

(74 reference statements)

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“…Neural stem/precursor cells (NSCs) are multipotent cells, capable of differentiating into the main phenotypes of the central nervous system, namely neurons, astrocytes and oligodendrocytes (Yi et al, 2013). NSCs can be isolated from developing or adult central nervous system tissue (Bennett et al, 2009;Meyer et al, 2010) and cultured in vitro as free-floating spheres (neurospheres) in the presence of endothelium growth factor and/or basic fibroblast growth factor (Bonnamain et al, 2012).…”

Section: Neural Stem Cellsmentioning

confidence: 99%

Old and new challenges in Parkinson's disease therapeutics

Pires

Teixeira

Mendes-Pinheiro

et al. 2017

Progress in Neurobiology

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored.

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Section: Neural Stem Cellsmentioning

confidence: 99%

Old and new challenges in Parkinson's disease therapeutics

Pires

Teixeira

Mendes-Pinheiro

et al. 2017

Progress in Neurobiology

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“…To overcome these barriers, many researchers are exploring the clinical use of stem cells in gene therapies designed to treat cancer. Stem cells are capable of self-renewal, multilineage differentiation and inherent migration to tumor sites (19).…”

Section: Additional Effects Of Engineered Stem Cells Expressing a Thementioning

confidence: 99%

Additional effects of engineered stem cells expressing a therapeutic gene and interferon-β in a xenograft mouse model of endometrial cancer

Kim

Choi

2015

International Journal of Oncology

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Abstract. Endometrial cancer is the most common gynecologic malignancy in women worldwide. In the present study, we evaluated the effects of neural stem cell-directed enzyme/prodrug therapy (NDEPT) designed to more selectively target endometrial cancer. For this, we employed two different types of neural stem cells (NSCs), HB1.F3.CD and HB1.F3.CD.IFN-β cells. Cytosine deaminase (CD) can convert the non-toxic prodrug, 5-fluorocytosine (5-FC), into a toxic agent, 5-fluorouracil (5-FU), which inhibits DNA synthesis. IFN-β is a powerful cytotoxic cytokine that is released by activated immune cells or lymphocytes. In an animal model xenografted with endometrial Ishikawa cancer cells, the stem cells stained with CM-DiI were injected into nearby tumor masses and 5-FC was delivered by intraperitoneal injection. Co-expression of CD and IFN-β significantly inhibited the growth of cancer (~50-60%) in the presence of 5-FC. Among migration-induced factors, VEGF gene was highly expressed in endometrial cancer cells. Histological analysis showed that the aggressive nature of cancer was inhibited by 5-FC in the mice treated with the therapeutic stem cells. Furthermore, PCNA expression was more decreased in HB1.F3.CD.IFN-β treated mice rather than HB1.F3.CD treated mice. To confirm the in vitro combined effects of 5-FU and IFN-β, 5-FU was treated in Ishikawa cells. 5-FU increased the IFN-β/receptor 2 (IFNAR2) and BXA levels, indicating that 5-FU increased sensitivity of endometrial cancer cells to IFN-β, leading to apoptosis of cancer cells. Taken together, these results provide evidence for the efficacy of therapeutic stem cell-based immune therapy involving the targeted expression of CD and IFN-β genes at endometrial cancer sites.

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“…phenotype, reducing the likelihood for tumor growth. 83 NSCs have been shown to be an effective neural repair strategy in preclinical models of injury owing to their inherent ability to provide neuroprotection, decrease immunoreactivity, and secrete neurotrophic factors, such as glial-derived neurotrophic factor and brain-derived neurotrophic factor. 84 Previous work has also shown that NSCs can differentiate into dopaminergic-like cells, survive transplantation, integrate with the host architecture, and improve functional recovery.…”

Section: Regenerative Medicinementioning

confidence: 99%

Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease

Harris

Burrell

Struzyna

et al. 2020

npj Parkinsons Dis.

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Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease, affecting 1–2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway. Regenerative medicine-based solutions are being aggressively pursued with the goal of restoring dopamine levels in the striatum, with several emerging techniques attempting to reconstruct the entire nigrostriatal pathway—a key goal to recreate feedback pathways to ensure proper dopamine regulation. Although many pharmacological, genetic, and optogenetic treatments are being developed, this article focuses on the evolution of transplant therapies for the treatment of PD, including fetal grafts, cell-based implants, and more recent tissue-engineered constructs. Attention is given to cell/tissue sources, efficacy to date, and future challenges that must be overcome to enable robust translation into clinical use. Emerging regenerative medicine therapies are being developed using neurons derived from autologous stem cells, enabling the construction of patient-specific constructs tailored to their particular extent of degeneration. In the upcoming era of restorative neurosurgery, such constructs may directly replace SNpc neurons, restore axon-based dopaminergic inputs to the striatum, and ameliorate motor deficits. These solutions may provide a transformative and scalable solution to permanently replace lost neuroanatomy and improve the lives of millions of people afflicted by PD.

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Development and application of neural stem cells for treating various human neurological diseases in animal models

Cited by 24 publications

References 68 publications

Old and new challenges in Parkinson's disease therapeutics

Old and new challenges in Parkinson's disease therapeutics

Additional effects of engineered stem cells expressing a therapeutic gene and interferon-β in a xenograft mouse model of endometrial cancer

Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease

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