scholarly journals Potential Therapeutic Effects of the Neural Stem Cell-Targeting Antibody Nilo1 in Patient-Derived Glioblastoma Stem Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Gorjana Rackov ◽  
Giorgia Iegiani ◽  
Daniel Uribe ◽  
Claudia Quezada ◽  
Cristóbal Belda-Iniesta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Therapeutic Effects ◽  
Cell Targeting ◽  
Glioblastoma Stem Cells

Glioblastoma stem cells and stem cell-targeting immunotherapies

2015 ◽  
Vol 123 (3) ◽  
pp. 449-457 ◽  
Author(s):  
Rogelio Esparza ◽  
Tej D. Azad ◽  
Abdullah H. Feroze ◽  
Siddhartha S. Mitra ◽  
Samuel H. Cheshier
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Targeting ◽  
Glioblastoma Stem Cells

scholarly journals Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice

2016 ◽  
Vol 36 (12) ◽  
pp. 2134-2145 ◽  
Author(s):  
Takuma Wakai ◽  
Purnima Narasimhan ◽  
Hiroyuki Sakata ◽  
Eric Wang ◽  
Hideyuki Yoshioka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Intracerebral Hemorrhage ◽  
Neural Stem Cells ◽  
Cell Survival ◽  
Neural Stem Cell ◽  
Hypoxic Preconditioning ◽  
Neurological Deficits ◽  
Therapeutic Effects ◽  
Cell Recovery

Previous studies have shown that intraparenchymal transplantation of neural stem cells ameliorates neurological deficits in animals with intracerebral hemorrhage. However, hemoglobin in the host brain environment causes massive grafted cell death and reduces the effectiveness of this approach. Several studies have shown that preconditioning induced by sublethal hypoxia can markedly improve the tolerance of treated subjects to more severe insults. Therefore, we investigated whether hypoxic preconditioning enhances neural stem cell resilience to the hemorrhagic stroke environment and improves therapeutic effects in mice. To assess whether hypoxic preconditioning enhances neural stem cell survival when exposed to hemoglobin, neural stem cells were exposed to 5% hypoxia for 24 hours before exposure to hemoglobin. To study the effectiveness of hypoxic preconditioning on grafted-neural stem cell recovery, neural stem cells subjected to hypoxic preconditioning were grafted into the parenchyma 3 days after intracerebral hemorrhage. Hypoxic preconditioning significantly enhanced viability of the neural stem cells exposed to hemoglobin and increased grafted-cell survival in the intracerebral hemorrhage brain. Hypoxic preconditioning also increased neural stem cell secretion of vascular endothelial growth factor. Finally, transplanted neural stem cells with hypoxic preconditioning exhibited enhanced tissue-protective capability that accelerated behavioral recovery. Our results suggest that hypoxic preconditioning in neural stem cells improves efficacy of stem cell therapy for intracerebral hemorrhage.

scholarly journals Cereblon-Based Small-Molecule Compounds to Control Neural Stem Cell Proliferation in Regenerative Medicine

2021 ◽  
Vol 9 ◽  
Author(s):  
Tomomi Sato ◽  
Takumi Ito ◽  
Hiroshi Handa
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Brain Size ◽  
Therapeutic Effects ◽  
Sedative Drug

Thalidomide, a sedative drug that was once excluded from the market owing to its teratogenic properties, was later found to be effective in treating multiple myeloma. We had previously demonstrated that cereblon (CRBN) is the target of thalidomide embryopathy and acts as a substrate receptor for the E3 ubiquitin ligase complex, Cullin-Ring ligase 4 (CRL4CRBN) in zebrafish and chicks. CRBN was originally identified as a gene responsible for mild intellectual disability in humans. Fetuses exposed to thalidomide in early pregnancy were at risk of neurodevelopmental disorders such as autism, suggesting that CRBN is involved in prenatal brain development. Recently, we found that CRBN controls the proliferation of neural stem cells in the developing zebrafish brain, leading to changes in brain size. Our findings imply that CRBN is involved in neural stem cell growth in humans. Accumulating evidence shows that CRBN is essential not only for the teratogenic effects but also for the therapeutic effects of thalidomide. This review summarizes recent progress in thalidomide and CRBN research, focusing on the teratogenic and therapeutic effects. Investigation of the molecular mechanisms underlying the therapeutic effects of thalidomide and its derivatives, CRBN E3 ligase modulators (CELMoDs), reveals that these modulators provide CRBN the ability to recognize neosubstrates depending on their structure. Understanding the therapeutic effects leads to the development of a novel technology called CRBN-based proteolysis-targeting chimeras (PROTACs) for target protein knockdown. These studies raise the possibility that CRBN-based small-molecule compounds regulating the proliferation of neural stem cells may be developed for application in regenerative medicine.

scholarly journals A Core Regulatory Circuit in Glioblastoma Stem Cells Links MAPK Activation to a Transcriptional Program of Neural Stem Cell Identity

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Gregory Riddick ◽  
Svetlana Kotliarova ◽  
Virginia Rodriguez ◽  
H. S. Kim ◽  
Amanda Linkous ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Transcriptional Program ◽  
Mapk Activation ◽  
Glioblastoma Stem Cells ◽  
Cell Identity ◽  
Regulatory Circuit

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

scholarly journals DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4011
Author(s):  
Brianna Chen ◽  
Dylan McCuaig-Walton ◽  
Sean Tan ◽  
Andrew P. Montgomery ◽  
Bryan W. Day ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Cellular Heterogeneity ◽  
Differentiation Potential ◽  
Glioblastoma Stem Cells ◽  
Glioblastoma Stem Cell

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

Enhancing therapeutic effects and in vivo tracking of adipose tissue derived mesenchymal stem cells for liver injury using bioorthogonal click chemistry

Nanoscale ◽  
2020 ◽  
Author(s):  
Naishun Liao ◽  
Da Zhang ◽  
Ming Wu ◽  
Huang-Hao Yang ◽  
Xiaolong Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Liver Injury ◽  
Mesenchymal Stem Cell ◽  
Liver Diseases ◽  
Therapeutic Effects

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...

scholarly journals Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cell Therapy ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Stem Cell Maintenance ◽  
Selection Of

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

scholarly journals Regenerative Cardiovascular Therapies: Stem Cells and Beyond

2019 ◽  
Vol 20 (6) ◽  
pp. 1420 ◽  
Author(s):  
Bernhard Wernly ◽  
Moritz Mirna ◽  
Richard Rezar ◽  
Christine Prodinger ◽  
Christian Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Basic Science ◽  
Left Ventricular ◽  
Specific Cell ◽  
Therapeutic Effects ◽  
Cell Processing

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.

The Neural Stem Cell Lineage Reveals Novel Relationships Among Spermatogonial Germ Stem Cells and Other Pluripotent Stem Cells

2014 ◽  
Vol 23 (7) ◽  
pp. 767-778 ◽  
Author(s):  
Anouk-Martine Teichert ◽  
Schreiber Pereira ◽  
Brenda Coles ◽  
Radha Chaddah ◽  
Susan Runciman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cell Lineage ◽  
Stem Cell Lineage
Sign in / Sign up

Export Citation Format

Share Document