Stem cell therapy in Alzheimer’s disease: possible benefits and limiting drawbacks

Author: Alipour, Masoume; Nabavi, Seyed Massood; Arab, Leila; Vosough, Massoud; Pakdaman, Hossein; Ehsani, Ehsan; Shahpasand, Koorosh Description: Alzheimer’s disease (AD) is the sixth leading cause of death globally and the main reason for dementia in elderly people. AD is a long-term and progressive neurodegenerative disorder that steadily worsens memory and communicating skills eventually leads to a disabled person of performing simple daily tasks. Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating…

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Small-Molecule Prodigiosin Restores p53 Tumor Suppressor Activity in Chemoresistant Colorectal Cancer Stem Cells via c-Jun-Mediated delta-Np73 Inhibition and p73 Activation

Author: Prabhu, Varun V.; Hong, Bo; Allen, Joshua E.; Zhang, Shengliang; Lulla, Amriti R.; Dicker, David T.; El-Deiry, Wafik S. Description: Tumor suppressor p53 is frequently mutated or inactivated in colorectal cancer. In contrast, p53 family member p73 is rarely mutated in colorectal cancer and p73 activation elicits p53-like tumor suppression. Colorectal cancer stem cells (CRCSC) comprise a rare self-renewing subpopulation that contributes to tumor maintenance and chemoresistance. p53 restoration is known to target CRCSCs, but p73 restoration in CRCSCs has not been examined. In this study, we investigated the…

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Ethical and social considerations of stem cell research

Author: McLaren, A. Description: Much recent interest has focused on whether stem cell therapy could alleviate or even cure common degenerative diseases. This has been accompanied by debate on the ethics of destructive research on early human embryos. Stem cells derived from various sources raise different ethical issues, but their contribution to medical research could be immense. Any use of stem cells should be subject to appropriate scientific and ethical review. Subject headings: Bioethics; Embryo, Mammalian; Ethics, Medical; Humans; Morals; Public Policy; Research; Sociology; Stem Cells; Therapy Publication year: 2001…

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Breast cancer stem cells, EMT and therapeutic targets

Author: Kotiyal, S.; Bhattacharya, S. Description: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT…

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Autophagy Supports Breast Cancer Stem Cell Maintenance by Regulating IL6 Secretion

Author: Maycotte, Paola; Jones, Kenneth L.; Goodall, Megan L.; Thorburn, Jacqueline; Thorburn, Andrew Description: Autophagy is a mechanism by which cells degrade cellular material to provide nutrients and energy for survival during stress. The autophagy is thought to be a critical process for cancer stem cell (CSC) or tumor-initiating cell maintenance but the mechanisms by which autophagy supports survival of CSCs remain poorly understood. In this study, inhibition of autophagy by knockdown of ATG7 or BECN1 modified the CD44(+)/CD24(low/-) population in breast cancer cells by regulating CD24 and IL6 secretion….

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Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1

Author: Nguyen, Phong Dang; Hollway, Georgina Elizabeth; Sonntag, Carmen; Miles, Lee Barry; Hall, Thomas Edward; Berger, Silke; Fernandez, Kristine Joy; Gurevich, David Baruch; Cole, Nicholas James; Alaei, Sara; Ramialison, Mirana; Sutherland, Robert Lyndsay; Polo, Jose Maria; Lieschke, Graham John; Currie, Peter David Description: Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vasculature by a series of poorly understood inductive events. Previous studies have…

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Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling

Author: Kobayashi, Isao; Kobayashi-Sun, Jingjing; Kim, Albert D.; Pouget, Claire; Fujita, Naonobu; Suda, Toshio; Traver, David Description: Notch signalling plays a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development and requires intimate contact between signal-emitting and signal-receiving cells, although little is known regarding when, where and how these intercellular events occur. We previously reported that the somitic Notch ligands, Dlc and Dld, are essential for HSC specification. It has remained unclear, however, how these somitic requirements are connected to the later emergence of HSCs from…

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Discrete Notch signaling requirements in the specification of hematopoietic stem cells

Author: Kim, Albert D.; Melick, Chase H.; Clements, Wilson K.; Stachura, David L.; Distel, Martin; Panakova, Daniela; MacRae, Calum; Mork, Lindsey A.; Crump, J. Gage; Traver, David Description: Hematopoietic stem cells (HSCs) require multiple molecular inputs for proper specification, including activity of the Notch signaling pathway. A requirement for the Notch1 and dispensability of the Notch2 receptor has been demonstrated in mice, but the role of the remaining Notch receptors has not been investigated. Here, we demonstrate that three of the four Notch receptors are independently required for the specification…

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Ethical development of stem-cell-based interventions

Author: MacPherson, Amanda; Kimmelman, Jonathan Description: The process of developing new and complex stem-cell-based therapeutics is incremental and requires decades of sustained collaboration among different stakeholders. In this Perspective, we address key ethical and policy challenges confronting the clinical translation of stem-cell-based interventions (SCBIs), including premature diffusion of SCBIs to clinical practice, assessment of risk in trials, obtaining valid informed consent for research participants, balanced and complete scientific reporting and public communications, regulation, and equitable access to treatment. We propose a way forward for translating these therapies with the above…

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Cardiovascular regeneration in non-mammalian model systems: what are the differences between newts and man?

Author: Borchardt, Thilo; Braun, Thomas Description: The mammalian heart cannot regenerate substantial cardiac injuries, while certain non-mammalian vertebrates such as certain fish (Danio rerio) and amphibiae (Notophthalmus viridescens) are able to repair the heart without functional impairment. In mammalians, the prevailing repair process is accompanied by fibrosis and scarring, while zebrafish and newts can replace lost contractile tissue by newly formed cardiac muscle with only little or no scar formation. A better understanding of cardiac regeneration in non-mammalian vertebrates might provide new insights for the manipulation of regenerative pathways in…

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