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stem cell expansion

Parisa Tajer, Karin Pike-Overzet, Sagrario Arias, Menzo Havenga, Frank J T Staal
Expansion of hematopoietic stem cells (HSCs) for therapeutic purposes has been a "holy grail" in the field for many years. Ex vivo expansion of HSCs can help to overcome material shortage for transplantation purposes and genetic modification protocols. In this review, we summarize improved understanding in blood development, the effect of niche and conservative signaling pathways on HSCs in mice and humans, and also advances in ex vivo culturing protocols of human HSCs with cytokines or small molecule compounds...
February 18, 2019: Cells
Maojia Xu, Georgina Shaw, Mary Murphy, Frank Barry
There has been considerable interest in the generation of functional mesenchymal stromal cell (MSC) preparations from induced pluripotent stem cells (iMSCs) and this is now regarded as a potential source of unlimited, standardized, high-quality cells for therapeutic applications in regenerative medicine. While iMSCs meet minimal criteria for defining MSCs in terms of marker expression there are substantial differences in terms of trilineage potential, specifically a marked reduction in chondrogenic and adipogenic propensity in iMSCs compared to bone marrow-derived (BM) MSCs...
February 19, 2019: Stem Cells
Germán Wies, Anita Ida Mantese, Jorge José Casal, Gustavo Ángel Maddonni
BACKGROUND AND AIMS: Phytochrome B (phyB) is a photosensory receptor important for the control of plant plasticity and resource partitioning. Whether phyB is required to optimize plant biomass accumulation in agricultural crops exposed to full sunlight is unknown. Here we investigated the impact of mutations in the genes that encode either phyB1 or phyB2 on plant growth and grain yield in field crops of Zea mays sown at contrasting population densities. METHODS: Plants of maize inbred line France 2 wild type (WT) and the isogenic mutants lacking either phyB1 or phyB2 (phyB1 and phyB2) were cultivated in the field during two seasons...
February 19, 2019: Annals of Botany
Sriram Bandi, Tatyana Tchaikovskaya, Sanjeev Gupta
Endogenous cell signals regulate tissue homeostasis and are significant for directing the fate of stem cells. During liver development, cytokines released from various cell types are critical for stem/progenitor cell differentiation and lineage expansions. To determine mechanisms in these stage-specific lineage interactions, we modeled potential effects of soluble signals derived from immortalized human fetal liver parenchymal cells on stem cells, including embryonic and induced pluripotent stem cells. For identifying lineage conversion and maturation, we utilized conventional assays of cell morphology, gene expression analysis and lineage markers...
January 28, 2019: Differentiation; Research in Biological Diversity
Fang Wei, Tong Zhang, Shu-Chou Deng, Jian-Chang Wei, Ping Yang, Qiang Wang, Zhuan-Peng Chen, Wang-Lin Li, Hua-Cui Chen, He Hu, Jie Cao
PD-L1 is critical for tumor cell escape from immune surveillance by inhibiting T cell function via the PD-1 receptor. Accumulating evidence demonstrates that anti-PD-L1 monoclonal antibodies might potently enhance antitumor effects in various tumors, but the effect of PD-L1 on colorectal cancer stem cells (CSCs) remains unclear. We observed high PD-L1 expression in CD133+ CD44+ colorectal CSCs and CSC-enriched tumorspheres. Altering PD-L1 expression promoted colorectal CSC self-renewal by increasing the expression of stemness genes, the CD133+ CD44+ cell population sizes and the ability to form tumorspheres...
February 15, 2019: Cancer Letters
Florent Campo-Paysaa, Jonathan Dw Clarke, Richard Jt Wingate
We use the transparency of zebrafish embryos to reveal the de novo generation of a simple squamous epithelium and identify the cellular architecture in the epithelial transition zone that ties this squamous epithelium to the columnar neuroepithelium within the embryo's brain. The simple squamous epithelium of the rhombencephalic roof plate is pioneered by distinct mesenchymal cells at the dorsal midline of the neural tube. Subsequently, a progenitor zone is established at the interface between columnar epithelium of the rhombic lip and the expanding squamous epithelium of the roof plate...
February 18, 2019: ELife
Anouk R Killaars, Joseph C Grim, Cierra J Walker, Ella A Hushka, Tobin E Brown, Kristi S Anseth
Bone marrow derived human mesenchymal stem cells (hMSCs) are a promising cell source for regenerative therapies; however, ex vivo expansion is often required to achieve clinically useful cells numbers. Recent results reveal that when MSCs are cultured in stiff microenvironments, their regenerative capacity can be altered in a manner that is dependent on time (e.g., a mechanical dosing analogous to a chemical one). It is hypothesized that epigenomic modifications are involved in storing these mechanical cues, regulating gene expression, and ultimately leading to a mechanical memory...
February 6, 2019: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Hongshuang Yu, Yuanyuan Tian, Ying Wang, Shin Mineishi, Yi Zhang
Graft-vs.-host disease (GVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Significant progresses have been made in defining the dichotomous role of dendritic cells (DCs) in the development of GVHD. Host-derived DCs are important to elicit allogeneic T cell responses, whereas certain donor-types of DCs derived from newly engrafted hematopoietic stem/progenitor cells (HSPCs) can amply this graft-vs.-host reaction. In contrast, some DCs also play non-redundant roles in mediating immune tolerance...
2019: Frontiers in Immunology
Nazmul Haque, Darius Widera, Noor Hayaty Abu Kasim
BACKGROUND: The response of stem cells to paracrine factors within the host's body plays an important role in the regeneration process after transplantation. The aim of this study was to determine the viability and paracrine factor profile of stem cells from human extracted deciduous teeth (SHED) pre-cultivated in media supplemented with either foetal bovine serum (FBS) or pooled human serum (pHS) in the presence of individual human sera (iHS). METHODS: SHED (n = 3) from passage 4 were expanded in FBS (FBS-SHED) or pHS (pHS-SHED) supplemented media until passage 7...
February 16, 2019: Advances in Experimental Medicine and Biology
Manar Abu Diab, Rachel Eiges
Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5'-UTR of the X-linked FMR1 gene. When CGGs expand beyond 200 copies, they lead to epigenetic gene silencing of the gene. In addition, the greater the allele size, the more likely it will become unstable and exhibit mosaicism for expansion size between and within tissues in affected individuals. The timing and mechanisms of FMR1 epigenetic gene silencing and repeat instability are far from being understood given the lack of appropriate cellular and animal models that can fully recapitulate the molecular features characteristic of the disease pathogenesis in humans...
February 15, 2019: Brain Sciences
Jarel K Gandhi, Travis Knudsen, Matthew Hill, Bhaskar Roy, Lori Bachman, Cynthia Pfannkoch-Andrews, Karina N Schmidt, Muriel M Metko, Michael J Ackerman, Zachary Resch, Jose S Pulido, Alan D Marmorstein
Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture...
February 15, 2019: Stem Cells Translational Medicine
Eduardo Anitua, Mar Zalduendo, María Troya
AIM: This study investigated the use of the autologous technology of plasma rich in growth factors (PRGF) as a human-based substitute to fetal bovine serum (FBS) in the culture of human dental pulp stem cells. MATERIALS & METHODS: Stem cell characterization was performed. Analysis of isolation, proliferation, migration, trilineage differentiation, senescence and cryopreservation were compared between FBS and PRGF. RESULTS: Human dental pulp stem cell cultures isolated and maintained with PRGF showed a significantly higher number of cells per explant than FBS cultures...
February 15, 2019: Regenerative Medicine
Ping Zhang, Jyothy Raju, Md Ashik Ullah, Raymond Au, Antiopi Varelias, Kate H Gartlan, Stuart D Olver, Luke D Samson, Elise Sturgeon, Nienke Zomerdijk, Judy Avery, Tessa Gargett, Michael P Brown, Lachlan J Coin, Devika Ganesamoorthy, Cheryl Hutchins, Gary R Pratt, Glen A Kennedy, A James Morton, Cameron I Curley, Geoffrey R Hill, Siok-Keen Tey
Purpose: Inducible caspase 9 ( iCasp9 ) is a cellular safety switch that can make T-cell therapy safer. The purpose of this phase I trial was to investigate the use of iCasp9 -transduced T-cell addback in adult patients undergoing haploidentical stem cell transplantation for high-risk hematologic malignancies. Patients and Methods: Patients undergoing myeloablative, CD34-selected haploidentical stem cell transplantation were treated with 0.5-1.0 × 106 /kg donor-derived iCasp9 -transduced T cells on day +25 or 26 post-transplant, with additional doses allowed for disease relapse, infection, or mixed chimerism...
February 14, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sadhna O Piryani, Yiqun Jiao, Angel Y F Kam, Yang Liu, Tuan Vo-Dinh, Benny J Chen, Nelson J Chao, Phuong L Doan
PURPOSE: Extracellular vesicles (EVs) are shed vesicles that bear a combination of nucleic acids and proteins. EVs are becoming recognized as a mode of cell-to-cell communication. Since hematopoietic stem cells (HSCs) reside in proximity to endothelial cells (ECs), we investigated whether EC-derived EVs could regulate HSC regeneration following ionizing radiation. METHODS AND MATERIALS: We generated EVs derived from primary murine marrow ECs. We sought to determine the response of irradiated hematopoietic stem and progenitor cells to syngeneic or allogeneic EVs in culture assays...
February 11, 2019: International Journal of Radiation Oncology, Biology, Physics
Mariana I Giassetti, Michela Ciccarelli, Jon M Oatley
The demand for food will increase to an unprecedented level over the next 30 years owing to human population expansion, thus necessitating an evolution that improves the efficiency of livestock production. Genetic gain to improve production traits of domestic animal populations is most effectively achieved via selective use of gametes from animals deemed to be elite, and this principle has been the basis of selective breeding strategies employed by humans for thousands of years. In modern-day animal agriculture, artificial insemination (AI) has been the staple of selective breeding programs, but it has inherent limitations for applications in beef cattle and pig production systems...
February 15, 2019: Annual Review of Animal Biosciences
Jie Gu, Yuxia Wang, Juan Gao, Shengnan Yuan, Yajing Chu, Yanhan Li, Weiping Yuan, Xiaomin Wang
Tet2 (member 2 of the Tet family) plays an important role in DNA demethylation modification, epigenetic regulation, and hematopoiesis. In our previous study, we found that Tet2 knockout mice progressively developed lymphocytic leukemia and myeloid leukemia with aging. However,the role of Tet2 in bone marrow microenvironment is unclear. Here in this study, we found that more Tet2-/- mesenchymal stem cells (MSCs) from bone marrow were in the G2/M cell cycle stages. The division time of Tet2-/- MSCs was shorter than that of the control cells...
January 25, 2019: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Ryan Donaghy, Xu Han, Krasimira Rozenova, Kaosheng Lv, Qinqin Jiang, Miriam Doepner, Roger A Greenberg, Wei Tong
Hematopoietic stem cell (HSC) homeostasis is controlled by cytokine receptor-mediated JAK2 signaling. We previously found that JAK2 is promptly ubiquitinated upon cytokine stimulation. Whether a competing JAK2 de-ubiquitination activity exists is unknown. LNK is an essential adaptor protein that constrains HSC expansion through dampening thrombopoietin (TPO)- induced JAK2 signaling. We show here that a LNK-associated lysine63 - (K63-) deubiquitinating (DUB) complex, BRISC attenuates HSC expansion through control of JAK2 signaling...
February 12, 2019: Blood
Deborah Stanco, Christian Caprara, Gianluca Ciardelli, Luca Mariotta, Mauro Gola, Greta Minonzio, Gianni Soldati
Adipose-derived stem cells (ASCs) are multipotent and immune-privileged mesenchymal cells, making them ideal candidates for therapeutic purposes to manage tendon disorders. Providing safe and regulated cell therapy products to patients requires adherence to good manufacturing practices. To this aim we investigated the in vitro tenogenic differentiation potential of ASCs using a chemically defined serum-free medium (SF) or a xenogenic-free human pooled platelet lysate medium (hPL) suitable for cell therapy and both supplemented with CTGF, TGFβ-3, BMP-12 and ascorbic acid (AA) soluble factors...
2019: PloS One
Kenneth A Fowler, Viktoria Vasilieva, Ekaterina Ivanova, Olga Rimkevich, Andrey Sokolov, Svetlana Abbasova, Eldar Kim, James M Coghill
Acute graft-versus-host disease (aGVHD) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation (HSCT). Previously, we demonstrated that CC-Chemokine Receptor 7 (CCR7) is critical for aGVHD pathogenesis but dispensable for beneficial graft-versus-leukemia (GVL) responses. As a result, we evaluated a fully human anti-CCR7 blocking antibody as a new approach to prevent aGVHD in preclinical models. Here we report that antibody R707 is able to block human CCR7 signaling and function in vitro in response to its two natural ligands...
February 12, 2019: American Journal of Transplantation
Hirotoshi Miyoshi, Chiaki Sato, Yuichiro Shimizu, Misa Morita
With the aim of establishing an effective method to expand hematopoietic stem/progenitor cells for application in hematopoietic stem cell transplantation, we performed ex vivo expansion of hematopoietic stem/progenitor cells derived from mouse fetal liver cells in three-dimensional cocultures with stromal cells. In these cocultures, stromal cells were first cultured within three-dimensional scaffolds to form stromal layers and then fetal liver cells containing hematopoietic cells were seeded on these scaffolds to expand the hematopoietic cells over the 2 weeks of coculture in a serum-containing medium without the addition of cytokines...
February 12, 2019: International Journal of Artificial Organs
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