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https://www.readbyqxmd.com/read/28718622/graphene-sheet-induced-global-maturation-of-cardiomyocytes-derived-from-human-induced-pluripotent-stem-cells
#1
Jiaxian Wang, Chang Cui, Haiyan Nan, Yuanfang Yu, Yini Xiao, Ellen Poon, Gang Yang, Xijie Wang, Chenchen Wang, Lingsong Li, Kenneth Richard Boheler, Xu Ma, Xin Cheng, Zhenhua Ni, Minglong Chen
Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, and physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate which is a biocompatible and superconductive material...
July 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#2
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28714970/bone-marrow-adipocytes-promote-the-regeneration-of-stem-cells-and-haematopoiesis-by-secreting-scf
#3
Bo O Zhou, Hua Yu, Rui Yue, Zhiyu Zhao, Jonathan J Rios, Olaia Naveiras, Sean J Morrison
Endothelial cells and leptin receptor(+) (LepR(+)) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER(+) progenitors, which represent ∼5% of LepR(+) cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28714470/essential-role-of-fbxl5-mediated-cellular-iron-homeostasis-in-maintenance-of-hematopoietic-stem-cells
#4
Yoshiharu Muto, Masaaki Nishiyama, Akihiro Nita, Toshiro Moroishi, Keiichi I Nakayama
Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#5
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#6
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28688581/persistent-and-inducible-neogenesis-repopulates-progenitor-renin-lineage-cells-in-the-kidney
#7
Linda Hickmann, Anne Steglich, Michael Gerlach, Moath Al-Mekhlafi, Jan Sradnick, Peter Lachmann, Maria Luisa S Sequeira-Lopez, R Ariel Gomez, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
Renin lineage cells (RLCs) serve as a progenitor cell reservoir during nephrogenesis and after renal injury. The maintenance mechanisms of the RLC pool are still poorly understood. Since RLCs were also identified as a progenitor cell population in bone marrow we first considered that these may be their source in the kidney. However, transplantation experiments in adult mice demonstrated that bone marrow-derived cells do not give rise to RLCs in the kidney indicating their non-hematopoietic origin. Therefore we tested whether RLCs develop in the kidney through neogenesis (de novo differentiation) from cells that have never expressed renin before...
July 6, 2017: Kidney International
https://www.readbyqxmd.com/read/28687990/cd34-negative-hematopoietic-stem-cells-show-distinct-expression-profiles-of-homing-molecules-that-limit-engraftment-in-mice-and-sheep
#8
Tomoyuki Abe, Yoshikazu Matsuoka, Yoshikazu Nagao, Yoshiaki Sonoda, Yutaka Hanazono
We and others have reported that human hematopoietic stem cells (HSCs) are also present in the CD34-negative (CD34(-)) fraction of human cord blood (CB). Here, we examined the hematopoietic engraftment potential of 13 or 18 lineage-negative (13Lin(-) or 18Lin(-)) CD34(+/-) cells from human CB in mice and sheep. Both 13Lin(-) and 18Lin(-) CD34(+) cells efficiently engrafted in mice irrespective of transplantation route, be it by tail-vein injection (TVI) or by intra-bone marrow injection (IBMI). These cells also engrafted in sheep after in utero fetal intra-hepatic injection (IHI)...
July 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28681151/three-dimensional-spatiotemporal-modeling-of-colon-cancer-organoids-reveals-that-multimodal-control-of-stem-cell-self-renewal-is-a-critical-determinant-of-size-and-shape-in-early-stages-of-tumor-growth
#9
Huaming Yan, Anna Konstorum, John S Lowengrub
We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal...
July 5, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28679949/aml-induced-osteogenic-differentiation-in-mesenchymal-stromal-cells-supports-leukemia-growth
#10
V Lokesh Battula, Phuong M Le, Jeffrey C Sun, Khoa Nguyen, Bin Yuan, Ximin Zhou, Sonali Sonnylal, Teresa McQueen, Vivian Ruvolo, Keith A Michel, Xiaoyang Ling, Rodrigo Jacamo, Elizabeth Shpall, Zhiqiang Wang, Arvind Rao, Gheath Al-Atrash, Marina Konopleva, R Eric Davis, Melvyn A Harrington, Catherine W Cahill, Carlos Bueso-Ramos, Michael Andreeff
Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, in particular in osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter the BM microenvironment to create a hospitable niche. Here, we report that acute myeloid leukemia (AML) cells, but not normal CD34+ or CD33+ cells, induce osteogenic differentiation in mesenchymal stromal cells (MSCs). In addition, AML cells inhibited adipogenic differentiation of MSCs. Mechanistic studies identified that AML-derived BMPs activate Smad1/5 signaling to induce osteogenic differentiation in MSCs...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28676663/3d-models-of-the-hematopoietic-stem-cell-niche-under-steady-state-and-active-conditions
#11
Lisa Rödling, Ivo Schwedhelm, Saskia Kraus, Karen Bieback, Jan Hansmann, Cornelia Lee-Thedieck
Hematopoietic stem cells (HSCs) in the bone marrow are able to differentiate into all types of blood cells and supply the organism each day with billions of fresh cells. They are applied to cure hematological diseases such as leukemia. The clinical need for HSCs is high and there is a demand for being able to control and multiply HSCs in vitro. The hematopoietic system is highly proliferative and thus sensitive to anti-proliferative drugs such as chemotherapeutics. For many of these drugs suppression of the hematopoietic system is the dose-limiting toxicity...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673932/integrin-%C3%AE-v%C3%AE-3-enhances-the-suppressive-effect-of-interferon-%C3%AE-on-hematopoietic-stem-cells
#12
Terumasa Umemoto, Yu Matsuzaki, Yoshiko Shiratsuchi, Michihiro Hashimoto, Takayuki Yoshimoto, Ayako Nakamura-Ishizu, Brian Petrich, Masayuki Yamato, Toshio Suda
Hematopoietic homeostasis depends on the maintenance of hematopoietic stem cells (HSCs), which are regulated within a specialized bone marrow (BM) niche. When HSC sense external stimuli, their adhesion status may be critical for determining HSC cell fate. The cell surface molecule, integrin αvβ3, is activated through HSC adhesion to extracellular matrix and niche cells. Integrin β3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-γ (IFNγ) and β3 integrin signaling in murine HSC function by a novel definitive phenotyping of HSCs...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28669446/inflammation-and-myeloproliferative-neoplasms
#13
REVIEW
Federico Lussana, Alessandro Rambaldi
Myeloproliferative neoplasms (MPN) include three main entities: Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Myelofibrosis (MF). MPN represent a unique model of the relationship between the clonal development of a hematologic malignancy and chronic inflammation. The neoplastic clone is the main driver of this inflammatory reaction as demonstrated by the curative effect of allogeneic stem cell transplantation which leads not only to a complete restore of the hematopoiesis, but also to regression of bone marrow fibrosis...
June 29, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28669077/lung-as-a-niche-for-hematopoietic-progenitors
#14
Isabella Borges, Isadora Sena, Patrick Azevedo, Julia Andreotti, Viviani Almeida, Ana Paiva, Gabryella Santos, Daniel Guerra, Pedro Prazeres, Luiza Lousado Mesquita, Luanny Souto de Barros Silva, Caroline Leonel, Akiva Mintz, Alexander Birbrair
Platelets are released from megakaryocytes. The bone marrow has been proposed to be the major site where this process occurs. Lefrançais et al. (2017) using state-of-the-art techniques including two-photon microscopy, in vivo lineage-tracing technologies, and sophisticated lung transplants reveal that the lung is also a primary site for platelet biogenesis. Strikingly, lung megakaryocytes can completely reconstitute platelet counts in the blood in mice with thrombocytopenia. This study also shows that hematopoietic progenitors, with capacity to repopulate the bone marrow after irradiation, are present in the lungs...
July 1, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28665863/the-role-of-skeletal-stem-cells-in-the-reconstruction-of-bone-defects
#15
Matthew P Murphy, Dre Irizarry, Michael Lopez, Alessandra L Moore, Ryan C Ransom, Michael T Longaker, Derek C Wan, Charles K F Chan
Craniofacial surgery, since its inauguration, has been the culmination of collaborative efforts to solve complex congenital, dysplastic, oncological, and traumatic cranial bone defects. Now, 50 years on from the first craniofacial meeting, the collaborative efforts between surgeons, scientists, and bioengineers are further advancing craniofacial surgery with new discoveries in tissue regeneration. Recent advances in regenerative medicine and stem cell biology have transformed the authors' understanding of bone healing, the role of stem cells governing bone healing, and the effects of the niche environment and extracellular matrix on stem cell fate...
June 29, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28662672/fibroblast-growth-factor-2-supports-osteoblastic-niche-cells-during-hematopoietic-homeostasis-recovery-after-bone-marrow-suppression
#16
Kyung-Ae Yoon, YeonSung Son, Young-Jin Choi, Joo-Hyun Kim, Je-Yoel Cho
BACKGROUND: Hematopoietic stem cell (HSC) maintenance requires a specific microenvironment. HSC niches can be activated by tissue damaging chemotherapeutic drugs and various cell signaling molecules such as SDF-1 and FGF, which might also result in bone marrow stress. Recent research has insufficiently shown that endosteal osteolineage cells and other niche constituents recover after marrow injury. METHODS: We investigated the role of FGF2 in the osteoblastic niche cells during hematopoietic homeostasis recovery after bone marrow injury...
June 29, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28660376/bone-metabolism-markers-and-angiogenic-cytokines-as-regulators-of-human-hematopoietic-stem-cell-mobilization
#17
Pantelis Tsirkinidis, Evangelos Terpos, Georgios Boutsikas, Athanasios Papatheodorou, Konstantinos Anargyrou, Eleni Lalou, Aglaia Dimitrakopoulou, Christina Kalpadakis, Konstantinos Konstantopoulos, Marina Siakantaris, Panayiotis Panayiotidis, Gerassimos Pangalis, Marie-Christine Kyrtsonis, Theodoros Vassilakopoulos, Maria K Angelopoulou
Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients' sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization...
June 28, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28660186/use-of-imaging-techniques-to-illuminate-dynamics-of-hematopoietic-stem-cells-and-their-niches
#18
REVIEW
Takayuki Morikawa, Keiyo Takubo
Continuous generation of blood cells over an organism's lifetime is supported by hematopoietic stem/progenitor cells (HSPCs) capable of producing all hematopoietic cell subtypes. Adult mammalian HSPCs are localized to bone marrow and regulated by their neighboring microenvironment, or "niche." Because interactions of HSPCs with their niches are highly dynamic and complex, the recent development of imaging technologies provides a powerful new tool to understand stem cell/niche biology. In this review, we discuss recent advances in our understanding of dynamic HSPC/niche interactions during development, homeostasis, disease states or aging with a focus on studies advanced by imaging analysis...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28658717/bone-marrow-on-a-chip-long-term-culture-of-human-hematopoietic-stem-cells-in-a-3d-microfluidic-environment
#19
Stefan Sieber, Lorenz Wirth, Nino Cavak, Marielle Koenigsmark, Uwe Marx, Roland Lauster, Mark Rosowski
Multipotent hematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to this date no in vitro model exists that truthfully mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, we present a novel 3D co-culture model, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic Multi-Organ-Chip (MOC)...
June 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28644814/learning-multimodal-parameters-a-bare-bones-niching-differential-evolution-approach
#20
Yue-Jiao Gong, Jun Zhang, Yicong Zhou
Most learning methods contain optimization as a substep, where the nondifferentiability and multimodality of objectives push forward the interplay of evolutionary optimization algorithms and machine learning models. The recently emerged evolutionary multimodal optimization (MMOP) technique enables the learning of diverse sets of effective parameters for the models simultaneously, providing new opportunities to the applications requiring both accuracy and diversity, such as ensemble, interactive, and interpretive learning...
June 20, 2017: IEEE Transactions on Neural Networks and Learning Systems
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