Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Ford, E. David; Pearlman, Jodie; Ruan, Travis; Manion, John; Waller, Matthew A.; Neely, G. Gregory; Caron, Leslie

doi:10.3390/cells9112517

Cited by 53 publications

(36 citation statements)

References 212 publications

(265 reference statements)

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“…AP staining was performed using an Alkaline Phosphat ase st a in ing k it ( EM D Millipore). For immunofluorescence staining, cells were cultured in plates, and fixed and immunostained using established standard protocols (1,20). After washing with immunostaining wash buffer, the cells were sealed with immune staining blocking buffer at room temperature for 60 min, and stained with primary antibodies at appropriate dilutions for 90 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells

et al. 2021

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Induced pluripotent stem cells (iPSCs) reprogrammed by somatic cells may be used as a potentially novel treatment regimen in stem cell regenerative medicine, particularly in the central nervous system (CNS). In the present study, iPSCs were generated using mouse embryonic fibroblasts by ectopic overexpression of Sox-2, Oct-3/4, Klf-4 and c-Myc, and cultured under the same conditions as that used for embryonic stem cells. The neuronal differentiation capacity of mouse iPSCs was examined, and the involvement of the formation of embryoid bodies was assessed. The results suggested that after 15 days of neuronal inducement, Nestin, Vimentin and Glast protein expression levels were significantly increased in the mouse iPSC-derived cells. Additionally, Bmi1, which is selectively expressed in differentiated postnatal adult stem cells. such as hematopoietic stem cells and neural stem cells, was required for establishment of the neuronal differentiation of mouse iPSCs. In order to assess the effects of Bmi1 in neuronal differentiation, Bmi1 expression levels were inhibited with the small molecule PTC-209. The results showed that inhibition of Bmi1 expression reduced the expression of neuronal markers, such as Nestin, compared with the controls. These results suggested that mouse iPSCs can be induced to achieve neuronal differentiation. More interestingly, Bmi1 was required during the neuronal differentiation of mouse iPSCs.

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Section: Methodsmentioning

confidence: 99%

“…Neuronal loss frequently results in neurological injury and underlies several neurological diseases (1,2). Treatments aimed to replace lost neurons have shown significant success, both in studies and when used clinically (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells

et al. 2021

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“…Dopamine (DA), a key neurotransmitter that transmits signals between neurons, plays an essential role in motor control. PD is the second-most-common age-related progressive neurodegenerative disorder caused by DA deficits in the striatum due to the destruction of DA-producing neurons located in the substantia nigra [ 52 , 53 , 54 ]. The initial symptoms are sometimes barely noticeable, such as tremors affecting one hand or the slowing of movement.…”

Section: Neurodegenerative Diseases and Stem Cell Therapy Strategimentioning

confidence: 99%

Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview

Sivandzade

Cucullo

2021

IJMS

129

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Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells’ capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells, providing a conducive environment that is in favor of regeneration, or protecting the existing healthy neurons and glial cells from further damage. Thus, in this review, the various types of stem cells, the current knowledge of stem-cell-based therapies in neurodegenerative diseases, and the recent advances in this field are summarized. Indeed, a better understanding and further studies of stem cell technologies cause progress into realistic and efficacious treatments of neurodegenerative disorders.

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“…IPSCs have been proposed to overcome ethical concerns about the use of human embryos. IPSCs can be very efficently differentiated to neurons and glial cells [ 49 , 50 , 51 ] and they have been proposed as a promising alternative for cell therapy in brain and spinal cord injury [ 39 ], as a tool to screen genetic bases of neurological diseases [ 52 ] or even as an approach to correct alterations in chronic neurodegenerative diseases [ 53 ]. However, a better understanding is still required to regulate the generation of specific neuronal and glial populations in a balanced and coordinated manner.…”

Section: Introduction: Neural and Mesenchymal Stem Cells And Neurmentioning

confidence: 99%

“…However, a better understanding is still required to regulate the generation of specific neuronal and glial populations in a balanced and coordinated manner. Furthermore, the increased risk of cancer related to the use of IPSCs is regarded as a major drawback for autologous personalized neuroregenerative therapy [ 49 ].…”

Section: Introduction: Neural and Mesenchymal Stem Cells And Neurmentioning

confidence: 99%

Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies

Luzuriaga

Polo

Pastor-Alonso

et al. 2021

IJMS

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Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.

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Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Cited by 53 publications

References 212 publications

Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells

Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells

Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview

Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies

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