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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/28529134/direct-reprogramming-epigenetics-and-cardiac-regeneration
#1
REVIEW
Shota Kurotsu, Takeshi Suzuki, Masaki Ieda
The discovery of induced pluripotent stem cells (iPSCs) has revolutionized regenerative medicine. Autologous iPSCs can be generated by introducing 4 stem cell-specific factors (Oct4, Sox2, Klf4, c-Myc) into fibroblasts. iPSCs can propagate indefinitely and differentiate into clinically important cell types including cardiomyocytes, in vitro. The iPSC-derived cardiomyocytes represent a promising source of cells for cell-based therapeutic approaches for cardiac regeneration. However, there are several challenges in the clinical application of iPSCs: tumorigenicity of immature cells, poor survival of the transplanted myocardial cells, and cost and efficacy of this therapeutic approach...
May 18, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28518147/survivin-a-key-player-in-cancer-progression-increases-in-obesity-and-protects-adipose-tissue-stem-cells-from-apoptosis
#2
Miriam Ejarque, Victòria Ceperuelo-Mallafré, Carolina Serena, Gisela Pachón, Yaiza Núñez-Álvarez, Margarida Terrón-Puig, Enrique Calvo, Catalina Núñez-Roa, Wilfredo Oliva-Olivera, Francisco J Tinahones, Miguel Angel Peinado, Joan Vendrell, Sonia Fernández-Veledo
Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28514935/mesenchymal-stem-cell-based-cartilage-regeneration-approach-and-cell-senescence-can-we-manipulate-cell-aging-and-function
#3
Marta Anna Szychlinska, Martin James Stoddart, Ugo D'Amora, Luigi Ambrosio, Mauro Alini, Giuseppe Musumeci
Aging is the most prominent risk factor triggering several degenerative diseases, such as Osteoarthritis (OA). Due to its poor self-healing capacity, once injured cartilage needs to be re-established. This process mighmight be approached bythrough resorting to cell-based therapies and/or tissue engineering. Human mesenchymal stem cells (hMSC) represent a promising approach due to their chondrogenic differentiation potential. Presently, in vitro chondrogenic differentiation of MSCs is limited by two main reasons: Aging aging of MSCs, which determines the loss of cell proliferative and differentiationed capacity and MSC-derived chondrocyte hypertrophic differentiation, which limits the use of these cells in cartilage tissue regeneration approach...
May 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28489652/histone-deacetylase-inhibitors-enhance-cytotoxicity-towards-breast-tumors-while-preserving-the-wound-healing-function-of-adipose-derived-stem-cells
#4
Kiavash R Koko, Shaohua Chang, Ashleigh L Hagaman, Marc W Fromer, Ryan S Nolan, John P Gaughan, Ping Zhang, Jeffrey P Carpenter, Spencer A Brown, Martha Matthews, Dorothy Bird
INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications...
June 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28464769/adult-stem-cell-therapy-for-cardiac-repair-in-patients-after-acute-myocardial-infarction-leading-to-ischemic-heart-failure-an-overview-of-evidence-from-the-recent-clinical-trials
#5
Rygiel Katarzyna
Cardiovascular diseases (CVD) still represent the leading cause of mortality worldwide, despite the remarkable advances in interventional cardiology, cardiac surgery, and modern pharmacotherapy, particularly in the setting of acute myocardial infarction (AMI), chronic ischemic heart failure (HF), cardiomyopathy (CM), and the associated left ventricular (LV) dysfunction. A significant loss of cardiomyocytes that underlies all of these conditions was previously considered irreversible. However, current evidence indicates that the human heart has some potential for repair, and over the past decade, many research studies have been exploring the use of stem cells (SCs) to facilitate restoration of myocardium...
May 1, 2017: Current Cardiology Reviews
https://www.readbyqxmd.com/read/28456748/reprogramming-acute-myeloid-leukemia-into-sensitivity-for-retinoic-acid-driven-differentiation
#6
REVIEW
Noortje van Gils, Han J M P Verhagen, Linda Smit
The success of all-trans retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL) provides a rationale to use retinoic acid-based therapy also for other subtypes of acute myeloid leukemia (AML). Recently, several studies showed that ATRA may efficiently drive leukemic cells into differentiation and/or apoptosis in a subset of AML patients with a NPM1 mutation, a FLT3-ITD, an IDH1 mutation, and patients overexpressing EVI-1. Since not all patients within these molecular subgroups respond to ATRA and clinical trials that tested ATRA response in non-APL AML patients have been very disappointing, the identification of additional biomarkers may help to identify patients that strongly respond to ATRA-based therapy...
April 26, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28453285/pharmacological-reprogramming-of-somatic-cells-for-regenerative-medicine
#7
Min Xie, Shibing Tang, Ke Li, Sheng Ding
Lost or damaged cells in tissues and organs can be replaced by transplanting therapeutically competent cells. This approach requires methods that effectively manipulate cellular identities and properties to generate sufficient numbers of desired cell types for transplantation. These cells can be generated by reprogramming readily available somatic cells, such as fibroblasts, into induced pluripotent stem cells (iPSCs), which can replicate indefinitely and give rise to any somatic cell type. This reprogramming can be achieved with genetic methods, such as forced expression of pluripotency-inducing transcription factors (TFs), which can be further improved, or even avoided, with pharmacological agents...
April 28, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28446316/-prognostic-value-of-recurrent-molecular-genetics-and-epigenetics-abnormity-in-t-lymphoblastic-lymphoma-leukemia-review
#8
Wei Guan, Yu Jing, Li Yu
T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence of various molecular genetic abnormalities. The NOTCH1 / FBXW7 mutation is one of the most common mutations, and related with good prognosis in T-LBL / ALL. PTEN mutation, a poor prognostic factor, could be overcome by NOTCH1 mutations in pediatric patients to some extent. Patients with MLL gene abnormality and loss of heterozygosity 6q have worse prognosis than those with normal karyotype. The incidence of MLL gene abnormality, RUNX1 mutation and DNMT3A mutation in early precursor T-lymphoblastic leukemia was higher than that of other mature subtypes, which could be used as risk stratification factors...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28441730/regulatory-mirnas-in-colorectal-carcinogenesis-and-metastasis
#9
REVIEW
Yongchen Guo, Yonghua Bao, Wancai Yang
Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in carcinogenesis and progression through regulating of oncogenic signaling pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-β, and inflammatory signaling pathways, stemness, and epithelial-mesenchymal transition, for carcinogenesis and metastasis in colorectal cancer...
April 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#10
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28423353/silencing-prdm14-expression-by-an-innovative-rnai-therapy-inhibits-stemness-tumorigenicity-and-metastasis-of-breast-cancer
#11
Hiroaki Taniguchi, Daisuke Hoshino, Chiharu Moriya, Hitoshi Zembutsu, Nobuhiro Nishiyama, Hiroyuki Yamamoto, Kazunori Kataoka, Kohzoh Imai
PR domain zinc finger protein 14 (PRDM14) maintains stemness in embryonic stem cells via epigenetic mechanisms. Although PRDM14 is elevated in several cancers, it is unclear if and how PRDM14 confers stem cell-like properties and epigenetic changes to cancer cells. Here, we examined the phenotypic characteristics and epigenetic and gene expression profiles of cancer cells that differentially express PRDM14, and assessed the potential of PRDM14-targeted cancer therapy. PRDM14 expression was markedly increased in many different cancer types and correlated with poor survival of breast cancer patients...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414326/mesenchymal-stem-cells-in-obesity-insights-for-translational-applications
#12
Kenichi Matsushita, Victor J Dzau
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28410601/the-diagnosis-and-management-of-nk-t-cell-lymphomas
#13
REVIEW
Eric Tse, Yok-Lam Kwong
Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and rarely as disseminated disease with a leukemic phase...
April 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28401192/evasion-of-targeted-cancer-therapy-through-stem-cell-like-reprogramming
#14
Kristine M Wadosky, Leigh Ellis, David W Goodrich
Prostate cancer variants expressing alternative lineage markers appear at relapse from antiandrogen therapy. We show that loss of the retinoblastoma (RB1) and tumor protein 53 (TP53) genes drives expression of stem cell reprogramming factors, lineage plasticity, and antiandrogen resistance. Epigenetic manipulation restores antiandrogen sensitivity-suggesting an approach for treating lethal prostate cancers.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28374184/brain-cancer-stem-cells-in-adults-and-children-cell-biology-and-therapeutic-implications
#15
REVIEW
Tamara J Abou-Antoun, James S Hale, Justin D Lathia, Stephen M Dombrowski
Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes...
April 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28367417/lovastatin-reduces-stemness-via-epigenetic-reprograming-of-bmp2-and-gata2-in-human-endometrium-and-endometriosis
#16
Mahdieh Taghizadeh, Mehrdad Noruzinia
OBJECTIVE: The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers...
April 2017: Cell Journal
https://www.readbyqxmd.com/read/28355380/induced-pluripotent-stem-cells-reprogramming-epigenetics-and-applications-in-the-regenerative-medicine
#17
Kátia Maria Sampaio Gomes, Ismael Cabral Costa, Jeniffer Farias Dos Santos, Paulo Magno Martins Dourado, Maria Fernanda Forni, Julio Cesar Batista Ferreira
Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated...
February 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#18
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28346436/detailed-comparison-of-retroviral-vectors-and-promoter-configurations-for-stable-and-high-transgene-expression-in-human-induced-pluripotent-stem-cells
#19
D Hoffmann, J W Schott, F K Geis, L Lange, F-J Müller, D Lenz, D Zychlinski, D Steinemann, M Morgan, T Moritz, A Schambach
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes...
May 2017: Gene Therapy
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#20
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
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