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Stem cell

Pablo Baquero, Amy Dawson, G Vignir Helgason
Despite the development of selective BCR-ABL-targeting tyrosine kinase inhibitors (TKIs) transforming the management of chronic myeloid leukaemia (CML), therapy-resistant leukaemic stem cells (LSCs) persist after TKI treatment and present an obstacle to a CML cure. Recently, we and others have made significant contributions to the field by unravelling survival dependencies in LSCs to work towards the goal of eradicating LSCs in CML patients. In this review, we describe these findings focusing on autophagy and mitochondrial metabolism, which have recently been uncovered as two essential processes for LSCs quiescence and survival, respectively...
September 17, 2018: FEBS Journal
Brandt C Huddle, Edward Grimley, Cameron D Buchman, Mikhail Chtcherbinine, Bikash Debnath, Pooja Mehta, Kun Yang, Cynthia A Morgan, Siwei Li, Jeremy Antonio Felton, Duxin Sun, Geeta Metha, Nouri Neamati, Ronald J Buckanovich, Thomas D Hurley, Scott D Larsen
Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore the structural determinants of ALDH1A isoform selectivity in a series of small molecule inhibitors in support of research into the role of ALDH1A in cancer stem cells. An SAR campaign guided by a co-crystal structure of the HTS hit CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily with excellent selectivity over the homologous ALDH2 isoform...
September 17, 2018: Journal of Medicinal Chemistry
Junko Ikemoto, Satoshi Yoshihara, Tamami Kobayashi, Shunro Kai, Yoshihiro Fujimori
In umbilical cord blood transplantation (UCBT), the number of cluster of differentiation (CD)34+ cells and colony‑forming units (CFUs) in the cord blood (CB) graft positively correlate with patient survival. Therefore, these parameters are currently used for quality assessment of the cryopreserved CB cells in the attached segment that is considered representative of the CB in the main bag prior to UCBT. Since aldehyde dehydrogenase (ALDH) activity is high in hematopoietic stem cells, the number of ALDH‑bright (ALDHbr) cells was examined in comparison with the number of CD34+ cells and CFUs for the quality assessment of CB units...
September 13, 2018: Molecular Medicine Reports
Yang Liu, Wanting Cao, Xiangbo Kong, Jie Li, Xueying Chen, Yaping Ge, Wanzhen Zhong, Silian Fang
Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial malignancy that arises following radiotherapy; progressive jaw necrosis severely decreases the quality of life of patients. Human bone marrow mesenchymal stem cells (hBMMSCs) are a cell type with self‑renewal and pluripotent differentiation potential in the bone marrow stroma. These cells are associated with bone tissue regeneration and are one of the primary cell types affected by bone tissue radiation injury. α‑2‑macroglobulin (α2M) is a glycoprotein‑rich macromolecule that interacts with cytokines, growth factors and hormones to serve a variety of biological roles...
September 4, 2018: Molecular Medicine Reports
Joana Marinho-Dias, João Lobo, Rui Henrique, Inês Baldaque, Carlos Pinho-Vaz, Luísa Regadas, Rosa Branca, Fernando Campilho, António Campos Jr, Rui Medeiros, Hugo Sousa
Post‑transplant lymphoproliferative disorder (PTLD), despite its rarity, is an important mortality/morbidity event in transplant patients. The purpose of the present study was to retrospectively examine the clinical and pathologic characteristics, and outcomes of PTLD at the Portuguese Oncology Institute of Porto. A retrospective review of patient information was performed for patients that developed PTLD following allogeneic hematopoietic stem cell transplant (aHSCT) and were diagnosed between 2005 and 2012...
September 3, 2018: Molecular Medicine Reports
Paul L Kaufman, Mary E Mohr, Scott P Riccomini, Carol A Rasmussen
Glaucoma is a chronic disease that can be challenging to treat for both patients and physicians. Most patients will require more than 1 medication over time to maintain their intraocular pressure (IOP) at a physiologically benign level. Patients may become refractory to existing compounds and many struggle with adherence to multiple topical drop regimens. The field of glaucoma therapeutics has been advancing rapidly with an emphasis on compounds comprising multiple molecules/mechanisms of action that offer additivity and are complementary to current therapeutics...
September 17, 2018: Asia-Pacific Journal of Ophthalmology
Sangho Kim, Kenji Hosoya, Ayumi Kobayashi, Masahiro Okumura
Peripheral blood stem cell (PBSC) transplantation following consolidation therapy is a feasible treatment option for canine hematological malignancies. In veterinary medicine, hematopoietic stem cells are generally mobilized into peripheral circulation using a granulocyte colony stimulating factor (G-CSF). This pilot study aimed to evaluate the hematopoietic stem cell mobilization effect of three different regimens for PBSC apheresis with Spectra Optia continuous mononuclear cell (CMNC) protocol in healthy dogs...
September 17, 2018: Veterinary and Comparative Oncology
Omid Emadian Saravi, Farshad Naghshvar, Zhila Torabizadeh, Somayeh Sheidaei
Background: Cancer stem cells (CSCs) are a group of tumor cells with self-renewal property and differentiation potential. CSCs play a crucial role in malignant progression of several types of tumors. However, what is still controversial is the clinicopathological relationship between Nanog marker and its prognostic value in the patients with breast cancer. The expression of Nanog in the patients with breast cancer and its correlation with clinicopathological prognostic factors was explored in the present study...
September 17, 2018: Iranian Biomedical Journal
Y L Lu, X M Zhang
Autoimmune uveitis is a major cause of visual disability. Treatment of chronic and recurrent uveitis can be extremely difficult, as various complications of it could impede the long-term usage of corticosteroids and immunosuppressants. Mesenchymal stem cells are of both immunosuppressive and neurotrophic effect, and can enhance the antimicrobial ability of the body, thereby hold great promise in clinical application for treating uveitis. (Chin J Ophthalmol, 2018, 54: 712-715) .
September 11, 2018: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
Rolla F Abu-Arja, Jamie L Dargart, Rajinder P S Bajwa, Samir B Kahwash, Jeffery J Auletta, Hemalatha G Rangarajan
AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant...
September 15, 2018: Pediatric Transplantation
Yasuo Takashima, Kenichi Horisawa, Miyako Udono, Yasuyuki Ohkawa, Atsushi Suzuki
Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer cases and has an extremely poor prognosis. Therefore, novel innovative therapies for HCC are strongly desired. As gene therapy tools for HCC, two hepatic transcription factors (TFs), HNF4A and HNF1A, have been employed to suppress proliferation and extinguish cancer-specific characteristics of target cells. However, our present data demonstrated that single transduction of HNF4A or HNF1A had only a limited effect on suppression of HCC cell proliferation...
September 16, 2018: Cancer Science
Lei Zhou, Dandan Sheng, Dong Wang, Wei Ma, Qiaodan Deng, Lu Deng, Suling Liu
Aldehyde dehydrogenases (ALDHs) defend intracellular homeostasis by catalyzing the conversion of toxic aldehydes into non-toxic carboxylic acids, which is of particular importance to the self-renewal of stem cells and cancer stem cells. The widely used ALDEFLUOR assay was initially designed to indicate the activity of ALDH1A1 in leukemia and has been demonstrated to detect the enzyme activity of several other ALDH isoforms in various cancer types in recent years. However, it is still elusive which isoforms, among the 19 ALDH isoforms in human genome, are the potential contributors in catalyzing ALDEFLUOR assay in different cancers...
September 15, 2018: Cell Biology and Toxicology
Kyoko Ito, Massimo Bonora, Keisuke Ito
HSCs have a fate choice when they divide; they can self-renew, producing new HSCs, or produce daughter cells that will mature to become committed cells. Technical challenges, however, have long obscured the mechanics of these choices. Advances in flow-sorting have made possible the purification of HSC populations, but available HSC-enriched fractions still include substantial heterogeneity, and single HSCs have proven extremely difficult to track and observe. Advances in single-cell approaches, however, have led to the identification of a highly purified population of hematopoietic stem cells (HSCs) that make a critical contribution to hematopoietic homeostasis through a preference for self-renewing division...
September 15, 2018: International Journal of Hematology
Natnita Mattawanon, Jessica B Spencer, David A Schirmer, Vin Tangpricha
Gender affirming procedures adversely affect the reproductive potential of transgender people. Thus, fertility preservation options should be discussed with all transpeople before medical and surgical transition. In transwomen, semen cryopreservation is typically straightforward and widely available at fertility centers. The optimal number of vials frozen depends on their reproductive goals and treatment options, therefore a consultation with a fertility specialist is optimal. Experimental techniques including spermatogonium stem cells (SSC) and testicular tissue preservation are technologies currently under development in prepubertal individuals but are not yet clinically available...
September 15, 2018: Reviews in Endocrine & Metabolic Disorders
Shayna Sharma, Mona Alharbi, Miharu Kobayashi, Andrew Lai, Dominic Guanzon, Felipe Zuñiga, Valeska Ormazabal, Carlos Palma, Katherin Scholz-Romero, Gregory E Rice, John D Hooper, Carlos Salomon
Ovarian cancer has resulted in over 140,000 deaths reported annually, worldwide. This is often attributed to cellular changes in the microenvironment, including increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs) to facilitate metastasis. Recently, the ability of exosomes to communicate signals between cells (and promote cancer progression) has been established. In this study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high=SKOV-3 and low=OVCAR-3) by differential and buoyant density centrifugation and characterized using nanoparticle tracking analysis, western blot and electron microscopy...
August 17, 2018: Clinical Science (1979-)
Benedetta Ermon, Claudia B Volpato, Giada Cattelan, Rosamaria Silipigni, Marina Di Segni, Chiara Cantaloni, Michela Casella, Peter P Pramstaller, Giulio Pompilio, Elena Sommariva, Viviana Meraviglia, Alessandra Rossini
Arrhythmogenic Cardiomyopathy (ACM) is an inherited cardiac disease characterized by arrhythmias and fibro-fatty replacement in the ventricular myocardium. Causative mutations are mainly reported in desmosomal genes, especially in plakophilin2 (PKP2). Here, using a virus-free reprogramming approach, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of one ACM patient carrying the frameshift heterozygous PKP2 mutation c.2569_3018del50. The iPSC line (EURACi004-A) showed the typical morphology of pluripotent cells, possessed normal karyotype and exhibited pluripotency markers and trilineage differentiation potential, including cardiomyogenic capability...
September 6, 2018: Stem Cell Research
Laura Montes-Medina, Alberto Hernández-Fernández, Araika Gutiérrez-Rivera, Purificación Ripalda-Cemboráin, Nerea Bitarte, Virginia Pérez-López, Froilán Granero-Moltó, Felipe Prosper, Ander Izeta
Acceleration of the consolidation of the distracted bone is a relevant medical need. As a platform to improve in vivo bone engineering, we developed a novel distraction osteogenesis (DO) model in a rabbit large bone (femur) and tested if the application of cultured bone marrow stromal cells (BMSCs) immediately after the osteotomy promotes the formation of bone. This report consists of two components, an animal study to evaluate the quality of the regenerate following different treatments and an in vitro study to evaluate osteogenic potential of BMSC cultures...
September 6, 2018: Injury
Hung Nguyen, Sydney Zarriello, Alexandreya Coats, Cannon Nelson, Chase Kingsbury, Anna Gorsky, Mira Rajani, Elliot G Neal, Cesar V Borlongan
Age-related neurological disorders continue to pose a significant societal and economic burden. Aging is a complex phenomenon that affects many aspects of the human body. Specifically, aging can have detrimental effects on the progression of brain diseases and endogenous stem cells. Stem cell therapies possess promising potential to mitigate the neurological symptoms of such diseases. However, aging presents a major obstacle for maximum efficacy of these treatments. In this review, we discuss current preclinical and clinical literature to highlight the interactions between aging, stem cell therapy, and the progression of major neurological disease states such as Parkinson's disease, Huntington's disease, stroke, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis, and multiple system atrophy...
September 13, 2018: Neurobiology of Disease
Zhi-Meng Xu, Feng Huang, Wei-Qiang Huang
Long noncoding RNAs (LncRNAs) are involved in biological processes and the pathology of diseases and represent an important biomarker or therapeutic target for disease. Emerging evidence has suggested that lncRNAs modulate angiogenesis by regulating the angiogenic cell process-including vascular endothelial cells (VECs); stem cells, particularly bone marrow-derived stem cells, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs); and vascular smooth muscle cells (VSMCs)-and participating in ischaemic heart disease (IHD)...
September 13, 2018: Life Sciences
Benjamin Fischer, Anna Meier, Annika Dehne, Aseem Salhotra, Thao Anh Tran, Sascha Neumann, Katharina Schmidt, Ina Meiser, Julia C Neubauer, Heiko Zimmermann, Luca Gentile
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase...
August 24, 2018: Stem Cell Research
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