Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats

Li, Mengjia; Wang, Zhengbo; Zheng, Tianqi; Huang, Tianzhuang; Liu, Baoguo; Han, Deqiang; Liu, Sumei; Liu, Bochao; Li, Mo; Si, Wei; Zhang, Y Alex; Niu, Yuyu; Chen, Zhiguo

doi:10.1155/2022/1396735

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…AAVS1-Pur-CAG-EGFP was purchased from Addgene (plasmid #80945) and used as a control. The guide RNA (gRNA) [15] target at AAVS1 was constructed in pX458 [19]. The plasmid sequences were tested by sequence screening.…”

Section: Methodsmentioning

confidence: 99%

Modulation of human induced neural stem cell-derived dopaminergic neurons by DREADD reveals therapeutic effects on a mouse model of Parkinson’s disease

Wang,

Han,

Zheng

et al. 2024

Preprint

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Background Stem cell-based therapy is a promising strategy for treating Parkinson’s disease (PD) characterized by the loss of dopaminergic neurons. Recently, induced neural stem cell-derived dopaminergic precursor cells (iNSC-DAPs) have been emerged as a promising candidate for PD cell therapy because of a lower tumor-formation ability. Designer receptors exclusively activated by designer drugs (DREADDs) are useful tools for examining functional synaptic connections with host neurons. Methods DREADD knock-in human iNSCs to express excitatory hM3Dq and inhibitory hM4Di receptors were engineered by CRISPR. The knock-in iNSCs were differentiated into midbrain dopaminergic precursor cells (DAPs) and transplanted into PD mice. The various behavior test such as the Apomorphine-induced rotation test, Cylinder test, Rotarod test, and Open field test were assessed at 4, 8, or 12 weeks post-transplantation with or without the administration of CNO. Electrophysiology were performed to assess the integrated condition and modulatory function to host neurons. Results DREADD expressing iNSC was constructed with normal neural stem cell characteristics, proliferation ability, and differentiation potential into dopaminergic neuorns. DAPs derived from DREADD expressing iNSC showed matched function upon administration of clozapine N-oxide (CNO) in vitro. The results of electrophysiology and behavioral tests of transplanted PD mouse models revealed that the grafts established synaptic connections with downstream host neurons and exhibited excitatory or inhibitory modulation in response to CNO in vivo. Conclusion iNSC-DAPs are a promising candidate for cell replacement therapy for Parkinson’s disease. Remote DREADD-dependent activation of iNSC-DAP neurons significantly enhanced the beneficial effects on transplanted mice with Parkinson’s disease.

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Section: Methodsmentioning

confidence: 99%

Modulation of human induced neural stem cell-derived dopaminergic neurons by DREADD reveals therapeutic effects on a mouse model of Parkinson’s disease

Wang,

Han,

Zheng

et al. 2024

Preprint

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“…DAergic differentiation of induced NSCs (iNSCs) is infancy and there are not as many DAergic differentiation protocols as the other two types of NSCs s. Induced NSCs from PBMNCs can be induced into mature DAergic neurons through a two-stage method. The first stage mediated the generation of DA progenitors mainly through FGF8 and SAG1, a SHH pathway agonist, and the second stage promoted the maturation of DA neurons through a combination of BDNF, GDNF, TGF-β3, AA and other soluble factors [ 44 , 88 , 89 ] . At the end of differentiation, about 60% of cultured cells co-expressed Foxa2 and TH.…”

Section: The Directional Differentiation Of Nscs From Different Sourc...mentioning

confidence: 99%

Directional induction of neural stem cells, a new therapy for neurodegenerative diseases and ischemic stroke

et al. 2023

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Due to the limited capacity of the adult mammalian brain to self-repair and regenerate, neurological diseases, especially neurodegenerative disorders and stroke, characterized by irreversible cellular damage are often considered as refractory diseases. Neural stem cells (NSCs) play a unique role in the treatment of neurological diseases for their abilities to self-renew and form different neural lineage cells, such as neurons and glial cells. With the increasing understanding of neurodevelopment and advances in stem cell technology, NSCs can be obtained from different sources and directed to differentiate into a specific neural lineage cell phenotype purposefully, making it possible to replace specific cells lost in some neurological diseases, which provides new approaches to treat neurodegenerative diseases as well as stroke. In this review, we outline the advances in generating several neuronal lineage subtypes from different sources of NSCs. We further summarize the therapeutic effects and possible therapeutic mechanisms of these fated specific NSCs in neurological disease models, with special emphasis on Parkinson’s disease and ischemic stroke. Finally, from the perspective of clinical translation, we compare the strengths and weaknesses of different sources of NSCs and different methods of directed differentiation, and propose future research directions for directed differentiation of NSCs in regenerative medicine.

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SH3 domain‐binding kinase 1 promotes proliferation and inhibits apoptosis of cervical cancer via activating the Wnt/β‐catenin and Raf/ERK1/2 signaling pathways

Chen

Sun

Zhou

et al. 2023

Molecular Carcinogenesis

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SH3 domain‐binding kinase 1 (SBK1), is a member of the serine/threonine protein kinases family, and was confirmed to be upregulated in cervical cancer in our previous study. Nonetheless, the role of SBK1 in regulating cancer occurrence and development is unclear. In this study, the stable SBK1‐knockdown and ‐overexpressed cell models were constructed by plasmid transfection technology. Cell viability and growth were assessed through CCK‐8, colony formation, and BrdU methods. Cell cycle and apoptosis were analyzed by flow cytometry. The JC‐1 staining assay was used to explore mitochondrial membrane potential. The scratch and Transwell assays were used to evaluate the cell metastatic ability. The nude mice models were utilized to explore the SBK1 expression affecting tumor growth in vivo. Our research indicated a high expression of SBK1 both in tissues and cells of cervical cancer. The proliferative, migratory, as well as invasive capacities of cervical cancer cells, were suppressed, and apoptosis was enhanced after SBK1 silence, whereas SBK1 upregulation led to opposite results. In addition, Wnt/β‐catenin and Raf/ERK1/2 pathways were activated by SBK1 upregulation. Furthermore, downregulation of c‐Raf or β‐catenin, reversed the proliferation promotion and apoptosis inhibition effects in SBK1‐overexpressed cells. The same results were observed with the use of the specific Raf inhibitor. SBK1 overexpression also contributed to tumor growth in vivo. Overall, SBK1 played a vital role in cervical tumorigenesis via activating the Wnt/β‐catenin and Raf/ERK1/2 pathways.

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Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats

Cited by 7 publications

References 35 publications

Modulation of human induced neural stem cell-derived dopaminergic neurons by DREADD reveals therapeutic effects on a mouse model of Parkinson’s disease

Modulation of human induced neural stem cell-derived dopaminergic neurons by DREADD reveals therapeutic effects on a mouse model of Parkinson’s disease

Directional induction of neural stem cells, a new therapy for neurodegenerative diseases and ischemic stroke

SH3 domain‐binding kinase 1 promotes proliferation and inhibits apoptosis of cervical cancer via activating the Wnt/β‐catenin and Raf/ERK1/2 signaling pathways

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