Specific combinations of the chromatin-modifying enzyme modulators significantly attenuate glioblastoma cell proliferation and viability while exerting minimal effect on normal adult stem cells growth

Tumor Biology ◽  
2015 ◽  
Vol 36 (11) ◽  
pp. 9067-9072
Author(s):  
Arshak R. Alexanian ◽  
Yi-Wen Huang
Physiology ◽  
2009 ◽  
Vol 24 (3) ◽  
pp. 171-185 ◽  
Author(s):  
Stephanie Z. Young ◽  
Angélique Bordey

Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA’s presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Saman Ghoraishizadeh ◽  
Afsoon Ghorishizadeh ◽  
Peyman Ghoraishizadeh ◽  
Nasibeh Daneshvar ◽  
Mohadese Hashem Boroojerdi

Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling which has a great influence on cell proliferation, differentiation, and biology. Recently, application of scaffolds and MSCs is being utilized in obtaining more homogenous population of MSCs with higher cell proliferation rate and greater differentiation potential, which are crucial factors in regenerative medicine. In this review, the definition, biology, source, characterization, and isolation of MSCs and current report of application of nanofibers in regenerative medicine in different lesions are discussed.


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii22-ii22
Author(s):  
V Kolesnikova ◽  
N Samoylenkova ◽  
S Drozd ◽  
A Revishchin ◽  
D Y Usachev ◽  
...  

Abstract BACKGROUND According to one of the theories, gliomas can occur as a result of dysregulation of stem cell division in the subventricular region of the brain. The CD133 membrane marker is a characteristic of both normal and tumor neural stem cells therefore it can be used to isolate a stem cell population from tumor tissue. Tumor cells actively proliferate which suggests that their possible differentiation may be achieved by inhibiting of their division as these two processes are mutually exclusive. For this purpose, G-quadruplex oligonucleotides together with neural-inducers such as a brain-derived neurotrophic factor (BDNF) may be used. MATERIAL AND METHODS Five cell cultures obtained from human glioblastoma tissues were analyzed for expression of CD133 using RT-qPCR. From cell culture with the highest level of CD133 using immunomagnetic separation CD133+ and CD133- cultures were received. CD133fr/peGFP-c1 recombinant DNA consisted of a CD133 second extracellular loop fragment and a peGFP-c1 vector was constructed to determine the localization of prominin-1, that is known as CD133 when found on cell membrane, using confocal microscopy. On chosen cell cultures an oligonucleotide bi-(AID-1-T) and its combination with BDNF were tested. The mechanism of GQ’s action is cytostatic and its non-toxicity properties were proved by flow cytometry. For evaluating the proliferative activity of cells MTT assay was performed on 10th and 20th days after exposure to the factors. RESULTS Cell culture G01 was chosen for further research as it had the highest level of the CD133. Colocalization of CD133 and GFP demonstrated a membrane localization of CD133 in cells with high expression level of this marker. MTT assay on 10th day after exposure to bi-(AID-1-T) as well as its combination with BDNF on cell culture G01 CD133- showed total inhibition of cell proliferation. The same combinations tested on G01 CD133+ cell culture demonstrated no difference in proliferative activity. After 20 days after exposure to bi-(AID-1-T) and combination of bi-(AID-1-T) with BDNF the significant decrease of G01 CD133+ cells’ proliferation was observed. When tested on whole glioblastoma cell culture G01 these combinations also showed significant inhibition of cell proliferation. CONCLUSION We showed that glioblastoma cells upon transfection with recombinant DNA, that contains a fragment of CD133, mainly have a membrane localization of this marker. It was observed that CD133+ cells are more stable to external influence that can be a proof of the fact that CD133 is charactered for glioblastoma stem cells. We tested the effect of an GQ bi-(AID-1-T) and its combination with BDNF and showed that BDNF is necessary for blocking proliferation of glioblastoma cells. Altogether, the results may be used for further research as it reveals a potential treatment for patients with glioblastoma. Grant №075-15-2020-809 (13.1902.21.0030).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lu Xue ◽  
Lingyu Bao ◽  
Julia Roediger ◽  
Yijun Su ◽  
Bingyin Shi ◽  
...  

Abstract Background Adult stem cells play an essential role in adult organ physiology and tissue repair and regeneration. While much has been learnt about the property and function of various adult stem cells, the mechanisms of their development remain poorly understood in mammals. Earlier studies suggest that the formation of adult mouse intestinal stem cells takes place during the first few weeks after birth, the postembryonic period when plasma thyroid hormone (T3) levels are high. Furthermore, deficiency in T3 signaling leads to defects in adult mouse intestine, including reduced cell proliferation in the intestinal crypts, where stem cells reside. Our earlier studies have shown that protein arginine methyltransferase 1 (PRMT1), a T3 receptor coactivator, is highly expressed during intestinal maturation in mouse. Methods We have analyzed the expression of PRMT1 by immunohistochemistry and studied the effect of tissue-specific knockout of PRMT1 in the intestinal epithelium. Results We show that PRMT1 is expressed highly in the proliferating transit amplifying cells and crypt base stem cells. By using a conditional knockout mouse line, we have demonstrated that the expression of PRMT1 in the intestinal epithelium is critical for the development of the adult mouse intestine. Specific removal of PRMT1 in the intestinal epithelium results in, surprisingly, more elongated adult intestinal crypts with increased cell proliferation. In addition, epithelial cell migration along the crypt-villus axis and cell death on the villus are also increased. Furthermore, there are increased Goblet cells and reduced Paneth cells in the crypt while the number of crypt base stem cells remains unchanged. Conclusions Our finding that PRMT1 knockout increases cell proliferation is surprising considering the role of PRMT1 in T3-signaling and the importance of T3 for intestinal development, and suggests that PRMT1 likely regulates pathways in addition to T3-signaling to affect intestinal development and/or homeostasis, thus affecting cell proliferating and epithelial turn over in the adult.


2014 ◽  
Vol 13 (1) ◽  
pp. 43
Author(s):  
Ira Arundina ◽  
Ketut Suardita

Stem cells provide new hope to fasten the healing process of various oral diseases including periodontal tissue(periodontitis). At present time, there is not yet found a material that can fix the teeth perfectly. Adult stem cells frombone marrow widely used for treatment. Numbers of stem cell are limited so growth factor is necessary to promoteproliferation of stem cells. Growth factor that has been used is expensive and difficult to get. Because of theseconstraints, it is necessary to develop alternative uses of medicinal plants as growth factor that accelerates woundhealing process. This study is aimed to proven what extent the potential Pegagan (Centella asiatica L) as a naturalgrowth factors to stem cells. The ability of proliferation and osteogenic differentiation in mesenchymal stem cells(MSC)was analyzed by adding terpenoid fraction of Centella asiatica. MTT assay data showed that the addition ofPegagan on cultured MSCs can increase stem cell proliferation. Pegagan increases the ability of MSC proliferationand differentiate into osteoblasts It is concluded that pegagan increase the ability of MSC proliferation anddifferentiate into osteoblasts.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Menon ◽  
Pasquale Creo ◽  
Marco Piccoli ◽  
Sonia Bergante ◽  
Erika Conforti ◽  
...  

Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Li ◽  
Ling Ji ◽  
Jieping Chen ◽  
Wengeng Zhang ◽  
Zhijia Ye

Cooperating with other signaling pathways, Wnt signaling controls cell proliferation, morphology, motility, and embryonic development destination and maintains the homeostasis of tissues including skin, blood, intestine, and brain by regulating somatic stem cells and their niches throughout adult life. Abnormal regulation of Wnt pathways leads to neoplastic proliferation in these tissues. Recent research shows that Wnt signaling is also associated with the regulation of cancer stem cells (CSCs) through a similar mechanism to that observed in normal adult stem cells. Thus, the Wnt/β-catenin signaling pathway has been intensively studied and characterized. For this review, we will focus on the regulation of the Wnt/β-catenin signaling pathway in skin cancer. With the important role in stemness and skin CSC proliferation, the Wnt/β-catenin signaling pathway and its elements have the potential to be targets for skin cancer therapy.


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