MiR-210-5p promotes the differentiation of human induced pluripotent stem cells into dopaminergic neural precursors by targeting SMAD4 and SUFU and treats parkinsonian rats

Lyu, Ying; Su, Zhongqiang; Ye, Guosheng; He, Xinkui; Liu, Yue; Yin, Q. Z.; Xie, Fanbing; Xu, Liping; Chen, Yuncai; Long, Dahong

doi:10.1016/j.exger.2023.112243

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…iPSC-derived autologous DA neurons offer an opportunity to solve the problems. Recently, most of the studies have shown that iPSC-derived DA neurons effectively restore motor function and effectively reinnervate the host brain without the potential threat of tumor formation [ 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ]. For instance, researchers employed small-molecule compounds to direct human iPSCs differentiation into nigral DA neurons that closely resembled in vivo counterparts [ 153 ].…”

Section: Cell Therapy Based On Ipsc Technologymentioning

confidence: 99%

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy

Zhang,

Qian,

Song

et al. 2024

IJMS

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Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based disease modeling and drug assessment primarily operated at the cellular level, recent years have witnessed a significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling the observation of disease progression and drug metabolism in an in vivo-like environment, surpassing the capabilities of iPSC-derived cells. Furthermore, iPSC-based cell therapy has emerged as a focal point of clinical interest. In this review, we provide an extensive overview of non-integrative reprogramming methods that have evolved since the inception of iPSC technology. We also deliver a comprehensive examination of iPSC-derived organoids, spanning the realms of the nervous system, cardiovascular system, and oncology, as well as systematically elucidate recent advancements in iPSC-related cell therapies.

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Section: Cell Therapy Based On Ipsc Technologymentioning

confidence: 99%

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy

Zhang,

Qian,

Song

et al. 2024

IJMS

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Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Comini,

Dowd

2024

Preprint

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Stem cell-based brain repair is a promising emergent therapy for Parkinson's which is based on years of foundational research using human fetal donors as a cell source. Unlike current therapeutic options for patients, this approach has the potential to provide long-term stem cell-derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients. The ultimate clinical success of stem cell-derived brain repair will depend on both the safety and efficacy of the approach, and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain. Because the pre-clinical literature suggests that there is a considerable variability in survival and differentiation between studies, the aim of this systematic review was to assess these parameters in human stem-derived dopaminergic progenitor transplant studies in animal models of Parkinson's. To do so, a defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024. After screening, 76 articles were included in the analysis from which 178 separate transplant studies were identified. From these, graft survival could be assessed in 52 studies and differentiation in 129 studies. Overall, we found that graft survival ranged from <1% to 500% of cells transplanted, with a median of 51% of transplanted cells surviving in the brain; while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%. This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors in order to maximize the therapeutic potential of this approach for patients.

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Pericyte-derived exosomal miR-210 improves mitochondrial function and inhibits lipid peroxidation in vascular endothelial cells after traumatic spinal cord injury by activating JAK1/STAT3 signaling pathway

Gao,

Yi,

Chen

et al. 2023

J Nanobiotechnol

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Background Spinal cord injury (SCI) remains a significant health concern, with limited available treatment options. This condition poses significant medical, economic, and social challenges. SCI is typically categorized into primary and secondary injuries. Inflammation, oxidative stress, scar formation, and the immune microenvironment impede axon regeneration and subsequent functional restoration. Numerous studies have shown that the destruction of the blood–brain barrier (BBB) and microvessels is a crucial factor in severe secondary injury. Additionally, reactive oxygen species (ROS)-induced lipid peroxidation significantly contributes to endothelial cell death. Pericytes are essential constituents of the BBB that share the basement membrane with endothelial cells and astrocytes. They play a significant role in the establishment and maintenance of BBB. Results Immunofluorescence staining at different time points revealed a consistent correlation between pericyte coverage and angiogenesis, suggesting that pericytes promote vascular repair via paracrine signaling. Pericytes undergo alterations in cellular morphology and the transcriptome when exposed to hypoxic conditions, potentially promoting angiogenesis. We simulated an early ischemia-hypoxic environment following SCI using glucose and oxygen deprivation and BBB models. Co-culturing pericytes with endothelial cells improved barrier function compared to the control group. However, this enhancement was reduced by the exosome inhibitor, GW4869. In vivo injection of exosomes improved BBB integrity and promoted motor function recovery in mice following SCI. Subsequently, we found that pericyte-derived exosomes exhibited significant miR-210-5p expression based on sequencing analysis. Therefore, we performed a series of gain- and loss-of-function experiments in vitro. Conclusion Our findings suggest that miR-210-5p regulates endothelial barrier function by inhibiting JAK1/STAT3 signaling. This process is achieved by regulating lipid peroxidation levels and improving mitochondrial function, suggesting a potential mechanism for restoration of the blood-spinal cord barrier (BSCB) after SCI.

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MiR-210-5p promotes the differentiation of human induced pluripotent stem cells into dopaminergic neural precursors by targeting SMAD4 and SUFU and treats parkinsonian rats

Cited by 3 publications

References 46 publications

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy

Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Pericyte-derived exosomal miR-210 improves mitochondrial function and inhibits lipid peroxidation in vascular endothelial cells after traumatic spinal cord injury by activating JAK1/STAT3 signaling pathway

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