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stem cell expansion

Hossein Tavassoli, Sanaz Naghavi Alhosseini, Andy Tay, Peggy P Y Chan, Steve Kah Weng Oh, Majid Ebrahimi Warkiani
Human stem cells, including pluripotent, embryonic and mesenchymal, stem cells play pivotal roles in cell-based therapies. Over the past decades, various methods for expansion and differentiation of stem cells have been developed to satisfy the burgeoning clinical demands. One of the most widely endorsed technologies for producing large cell quantities is using microcarriers (MCs) in bioreactor culture systems. In this review, we focus on microcarriers properties that can manipulate the expansion and fate of stem cells...
July 11, 2018: Biomaterials
Sherwin Ting, Alan Lam, Gerine Tong, Allen Chen, Heming Wei, JianJun Wu, Yue Ning Lam, Shaul Reuveny, Steve Oh
Human pluripotent stem cells (hPSCs) can be a renewable source for generating cardiomyocyte (CM) for treating myocardial infraction. In our previous publication, we described an integrated microcarrier-based wave reactor process for the expansion and differentiation of hPSCs to CMs on a rocker based platform. However, this platform is limited in terms of linear scalability and CMs purity. The present study describes ways to overcome these limitations by the use of a stirred scalable platform and incorporation of an additional lactate based purification step which increases CM purity...
August 1, 2018: Stem Cell Research
L Fouillet, E Daguenet, F Schein, E Tavernier, P Flandrin-Gresta, J Cornillon
Deciphering the mutational patterns and/or the biomarkers that might predict clinical response in patients with myelofibrosis is primordial to make treatment decisions. In this report, we discuss the clinical history, pathological evaluation, and genomics findings in a patient with JAK2-positive myelofibrosis who developed a secondary myelodysplasia after hematopoietic stem cell transplantation and JAK1/2 inhibitor treatment. Using next-generation sequencing, a paired comparison of relapse-specific versus primary tumour mutations highlighted the dynamic clonal evolution at relapse, showing concurrently the complete eradication of the JAK2-positive clone and the expansion of a second JAK2-negative clone with additional mutations...
August 7, 2018: Current Research in Translational Medicine
C Elabd, T E Ichim, K Miller, A Anneling, V Grinstein, V Vargas, F J Silva
BACKGROUND: Mesenchymal stem cells (MSCs) represent an attractive avenue for cellular therapies targeting degenerative diseases. MSC in vitro expansion is required in order to obtain therapeutic numbers during the manufacturing process. It is known that culture conditions impact cellular properties and behavior after in vivo transplantation. In this study, we aimed at evaluating the benefit of hypoxic culturing of human bone marrow derived mesenchymal stem cells on cell fitness and whole genome expression and discussed its implication on cellular therapies targeting orthopedic diseases such as chronic lower back pain...
August 10, 2018: Journal of Translational Medicine
Aaron B Bogutz, Rosemary Oh-McGinnis, Karen J Jacob, Rita Ho-Lau, Ting Gu, Marina Gertsenstein, Andras Nagy, Louis Lefebvre
The basic helix-loop-helix (bHLH) transcription factor ASCL2 plays essential roles in diploid multipotent trophoblast progenitors, intestinal stem cells, follicular T-helper cells, as well as during epidermal development and myogenesis. During early development, Ascl2 expression is regulated by genomic imprinting and only the maternally inherited allele is transcriptionally active in trophoblast. The paternal allele-specific silencing of Ascl2 requires expression of the long non-coding RNA Kcnq1ot1 in cis and the deposition of repressive histone marks...
August 10, 2018: PLoS Genetics
Alexandra E Butler, David Kirakossian, Tatyana Gurlo, Fuying Gao, Giovanni Coppola, Peter C Butler
The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche based on its coiled tubular structure embedded in mesenchyme, its proliferation and expansion in response to pancreatic injury, and the fact that it contains endocrine and exocrine epithelial cells. Little is known of the molecular signature of the PDG compartment in either a quiescent state or the potentially activated state during beta cell stress characteristic of diabetes. To address this, we performed RNA sequencing on RNA obtained from PDGs of wild type versus pre-diabetic HIP rats, a model of type 2 diabetes...
August 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Paola Bonetti, Montserrat Climent, Fabiana Panebianco, Chiara Tordonato, Angela Santoro, Matteo Jacopo Marzi, Pier Giuseppe Pelicci, Andrea Ventura, Francesco Nicassio
The role of the tumour-suppressor miR-34 family in breast physiology and in mammary stem cells (MaSCs) is largely unknown. Here, we revealed that miR-34 family, and miR-34a in particular, is implicated in mammary epithelium homoeostasis. Expression of miR-34a occurs upon luminal commitment and differentiation and serves to inhibit the expansion of the pool of MaSCs and early progenitor cells, likely in a p53-independent fashion. Mutant mice (miR34-KO) and loss-of-function approaches revealed two separate functions of miR-34a, controlling both proliferation and fate commitment in mammary progenitors by modulating several pathways involved in epithelial cell plasticity and luminal-to-basal conversion...
August 9, 2018: Oncogene
Dandan Li, Hui Li, Ying Wang, Ahmed Eldomany, Jing Wu, Chao Yuan, Jing Xue, Juan Shi, Yuanyuan Jia, Chunfang Ha, Shuxia Han, Xiaoming Liu, Jiali Yang, Dan Liu
Human endometrial epithelia undergo injury repair and regeneration with the menstrual cycle; however, mechanisms underpinning the roles of endometrial epithelial cells in endometrial lesions and regeneration remain incompletely understood, mainly owing to the difficulty in the isolation and expansion of primary endometrial epithelial cells and the lack of reliable models for in vitro and in vivo studies. In this report, we sought to improve methods for the isolation and expansion of human endometrial epithelial cells with a Rho-associated protein kinase (ROCK) inhibitor-modified medium and subsequently characterize endometrial epithelium generated with primary cells cultured in an air-liquid interface (ALI) state...
August 9, 2018: Stem Cell Research & Therapy
Melanie Gentil, Patricia Hugues, Christophe Desterke, Gladys Telliam, Ivan Sloma, Lucas E B Souza, Seda Baykal, Jerome Artus, Frank Griscelli, Agnes Guerci, Hyacinthe Johnson-Ansah, Adlen Foudi, Annelise Bennaceur-Griscelli, Ali G Turhan
Aryl Hydrocarbon Receptor (AHR) is an ubiquitous basic helix-loop-helix transcription factor, which is ligand-activated and involved in numerous biological processes including cell division, cell quiescence and inflammation. It has been shown that AHR is involved in normal hematopoietic progenitor proliferation in human cells. In addition, loss of AHR in knockout mice is accompanied by a myeloproliferative syndrome-like disease, suggesting a role of AHR in hematopoietic stem cell (HSC) maintenance. To study the potential role of AHR pathway in CML progenitors and stem cells, we have first evaluated the expression of AHR in UT-7 cell line expressing BCR-ABL...
2018: PloS One
Oshrat Attar-Schneider, Liat Drucker, Maya Gottfried
The fatality of non-small-cell lung cancer (NSCLC) and the role of the cancer microenvironment in its resistance to therapy are long recognized. Accumulating data allocate a significant role for mesenchymal stem cells (MSCs) in the malignant environment. Previously, we have demonstrated that MSCs from NSCLC metastatic bone marrow (BM) niche deleteriously affected NSCLC cells. Here, we have decided to examine the effect of MSCs from the primary niche of the lung (healthy or adjacent to tumor) on NSCLC phenotype...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kazuya Kobayashi, Ken Suzuki
Transplantation of stem/progenitor cells is a promising, emerging treatment for heart failure (HF) in the modern era. Mesenchymal stem/stromal cells (MSCs) are considered as one of the most promising cell sources for this purpose, because of their powerful secretion of reparative factors and immunomodulatory ability. To date, various sources of MSCs have been examined for the treatment of HF in preclinical or clinical studies, including adult tissues (bone marrow and adipose tissue), perinatal tissues (umbilical cord and amnion), and pluripotent stem cells (induced pluripotent stem cells and embryonic stem cells)...
August 9, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
Banaja P Dash, Tina M Schnöder, Carolin Kathner, Juliane Mohr, Sönke Weinert, Carolin Herzog, Parimala Sonika Godavarthy, Costanza Zanetti, Florian Perner, Rüdiger Braun-Dullaeus, Björn Hartleben, Tobias B Huber, Gerd Walz, Michael Naumann, Sarah Ellis, Valera Vasioukhin, Thilo Kähne, Daniela S Krause, Florian H Heidel
PURPOSE: Cell fate determinants Scrib and Llgl1 influence self-renewal capacity of hematopoietic stem cells (HSCs). Scrib-deficient HSCs are functionally impaired and lack sufficient repopulation capacity during serial transplantation and stress. In contrast, loss of Llgl1 leads to increased HSC fitness, gain of self-renewal capacity and expansion of the stem cell pool. Here, we sought to assess for shared and unique molecular functions of Llgl1 and Scrib by analyzing their interactome in hematopoietic cells...
August 6, 2018: Journal of Cancer Research and Clinical Oncology
Anahid Jewett, Janko Kos, Yuman Fong, Meng-Wei Ko, Tahmineh Safaei, Milica Perišić Nanut, Kawaljit Kaur
We have recently shown that natural killer (NK) cells select and differentiate cancer stem cells (CSCs)/undifferentiated tumors via secreted and membrane bound IFN-gamma (IFN-γ) and TNF-alpha (TNF-α), preventing tumor growth and inducing remodeling of the tumor microenvironment. Since many conventional therapeutic strategies, including chemotherapy and radiotherapy remain fairly unsuccessful in treating CSCs/poorly differentiated tumors, there has been an increasing interest in NK cell-targeted immunotherapy for the treatment of aggressive tumors...
August 3, 2018: Seminars in Cancer Biology
David P Steensma
Clonal hematopoiesis (CH)-an expansion of blood cells derived from a single hematopoietic stem cell-is a defining feature of hematologic cancers, but recently CH was also found to be a frequent consequence of aging. When aging-associated CH results from acquisition of a somatic mutation in a driver gene associated with leukemia, and this mutation is present at a variant allele frequency of at least 0.02 (2%) yet the patient does not meet World Health Organization diagnostic criteria for a hematologic neoplasm, this state is termed clonal hematopoiesis of indeterminate potential (CHIP)...
August 2018: Mayo Clinic Proceedings
David T Ewart, Erik J Peterson, Clifford J Steer
Technology for precise and efficient genetic editing is constantly evolving and is now capable of human clinical applications. Autoimmune and inflammatory diseases are chronic, disabling, sometimes life-threatening, conditions that feature heritable components. Both primary genetic lesions and the inflammatory pathobiology underlying these diseases represent fertile soil for new therapies based on the capabilities of gene editing. The ability to orchestrate precise targeted modifications to the genome will likely enable cell-based therapies for inflammatory diseases such as monogenic autoinflammatory disease, acquired autoimmune disease and for regenerative medicine in the setting of an inflammatory environment...
August 4, 2018: Annals of the Rheumatic Diseases
Carolin Göbel, Roman Goetzke, Thomas Eggermann, Wolfgang Wagner
Replicative senescence hampers application of mesenchymal stromal cells (MSCs) because it limits culture expansion, impairs differentiation potential, and hinders reliable standardization of cell products. MSCs can be rejuvenated by reprogramming into induced pluripotent stem cells (iPSCs), which is associated with complete erasure of age- and senescence-associated DNA methylation (DNAm) patterns. However, this process is also associated with erasure of cell-type and tissue-specific epigenetic characteristics that are not recapitulated upon re-differentiation towards MSCs...
August 3, 2018: Scientific Reports
Fatma Keklik, Ezzideen Barjes Alrawi, Qing Cao, Nelli Bejanyan, Armin Rashidi, Aleksandr Lazaryan, Patrick Arndt, Erhan H Dincer, Veronika Bachanova, Erica D Warlick, Margaret L MacMillan, Mukta Arora, Jeffrey Miller, Claudio G Brunstein, Daniel J Weisdorf, Celalettin Ustun
Diffuse alveolar hemorrhage after hematopoietic stem cell transplantation is a frequently fatal complication with no standard therapy. Although significant changes in supportive and intensive care measures for hematopoietic stem cell transplantation patients have been made over the past decades, the impact of these changes on the incidence and outcome of patients with diffuse alveolar hemorrhage has not been examined. We analyzed 1228 patients who underwent allogeneic hematopoietic stem cell transplantation between 2008-2015 at the University of Minnesota to study the incidence, risk factors, and outcomes of diffuse alveolar hemorrhage...
August 3, 2018: Haematologica
Abel Trujillo-Ocampo, Hyun-Woo Cho, Amanda C Herrmann, Wilfredo Ruiz-Vazquez, Andrew B Thornton, Hong He, Dan Li, Mariam A Qazilbash, Qing Ma, Steven A Porcelli, Elizabeth J Shpall, Jeffrey Molldrem, Jin S Im
BACKGROUND AIMS: CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT. METHODS: Human iNK T cells were first enriched from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting separation, then co-cultured with dendritic cells in the presence of agonist glycolipids, alpha-galactosylceramide, for 2 weeks...
July 31, 2018: Cytotherapy
Liani Devito, Matthew Donne, Nikola Kolundzic, Preeti Khurana, Carl Hobbs, Gabriel Kaddour, Sandrine Dubrac, Robert Gruber, Matthias Schmuth, Thea Mauro, Dusko Ilic
We have generated an induced pluripotent stem cell (iPSC) line KCLi001-A (iOP118) from a female atopic dermatitis (AD) patient, heterozygous for the loss-of-function mutation c.2282del4 in the filaggrin gene (FLG). Epidermal keratinocytes were reprogrammed using non-integrating Sendai virus vectors. The entire process of derivation and expansion of AD-iPSCs were performed under xeno-free culture conditions. Characterization of KCLi001-A line included molecular karyotyping, mutation screening using restriction enzyme digestion and Sanger sequencing, while pluripotency and differentiation potential were confirmed by expression of associated markers in vitro and by in vivo teratoma assay...
July 25, 2018: Stem Cell Research
Andrew Sinclair, Mary Beth O'Kelly, Tao Bai, Hsiang-Chieh Hung, Priyesh Jain, Shaoyi Jiang
Injectable and malleable hydrogels that combine excellent biocompatibility, physiological stability, and ease of use are highly desirable for biomedical applications. Here, a simple and scalable strategy is reported to make injectable and malleable zwitterionic polycarboxybetaine hydrogels, which are superhydrophilic, nonimmunogenic, and completely devoid of nonspecific interactions. When zwitterionic microgels are reconstructed, the combination of covalent crosslinking inside each microgel and supramolecular interactions between them gives the resulting zwitterionic injectable pellet (ZIP) constructs supportive moduli and tunable viscoelasticity...
July 31, 2018: Advanced Materials
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