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hematopoietic stem

Michael C Gundry, Lorenzo Brunetti, Angelique Lin, Allison E Mayle, Ayumi Kitano, Dimitrios Wagner, Joanne I Hsu, Kevin A Hoegenauer, Cliona M Rooney, Margaret A Goodell, Daisuke Nakada
Our understanding of the mechanisms that regulate hematopoietic stem/progenitor cells (HSPCs) has been advanced by the ability to genetically manipulate mice; however, germline modification is time consuming and expensive. Here, we describe fast, efficient, and cost-effective methods to directly modify the genomes of mouse and human HSPCs using the CRISPR/Cas9 system. Using plasmid and virus-free delivery of guide RNAs alone into Cas9-expressing HSPCs or Cas9-guide RNA ribonucleoprotein (RNP) complexes into wild-type cells, we have achieved extremely efficient gene disruption in primary HSPCs from mouse (>60%) and human (∼75%)...
October 25, 2016: Cell Reports
Ja Min Byun, Hea-Lim Kim, Dong-Yeop Shin, Youngil Koh, Sung-Soo Yoon, Moon-Woo Seong, Sung Sup Park, Jin Hee Kim, Yun-Gyoo Lee, Inho Kim
Pharmacogenomics can explain the inter-individual differences in response to drugs, including methotrexate (MTX) used for acute graft-versus-host disease (aGVHD) prophylaxis during hematopoietic stem cell transplantation (HSCT). In real-world practice, preplanned MTX dose is arbitrarily modified according to observed toxicity which can lead to unexpected and severe aGVHD development. We aimed to validate the influence of MTHFR C677T polymorphism on the outcomes of allogenic HSCT in a relatively under-represented homogenous Asian population...
2016: PloS One
Nidhi Sharma Dey, Parvathy Ramesh, Mayank Chugh, Sudip Mandal, Lolitika Mandal
Drosophila hematopoiesis bears striking resemblance with that of vertebrates, both in the context of distinct phases and the signaling molecules. Even though, there has been no evidence of Hematopoietic stem cells (HSCs) in Drosophila, the larval lymph gland with its Hedgehog dependent progenitors served as an invertebrate model of progenitor biology. Employing lineage-tracing analyses, we have now identified Notch expressing HSCs in the first instar larval lymph gland. Our studies clearly establish the hierarchical relationship between Notch expressing HSCs and the previously described Domeless expressing progenitors...
October 26, 2016: ELife
Casina Kan, Geoffrey Vargas, François Le Pape, Philippe Clézardin
Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts...
October 4, 2016: International Journal of Molecular Sciences
Hideki Sano, Kazuhiro Mochizuki, Mitsuko Akaihata, Shogo Kobayashi, Hitoshi Ohto, Atsushi Kikuta
Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT...
October 26, 2016: Pediatric Blood & Cancer
Emily S Tonorezos, Dana Barnea, Ghassan K Abou-Alfa, Jacqueline Bromberg, Michael D'Angelica, Charles A Sklar, Jinru Shia, Kevin C Oeffinger
Hepatocellular adenoma (HCA) is a rare benign epithelial neoplasm with potential for hemorrhage, rupture, or malignant transformation. Reported annual incidence of HCA is approximately 1/1,000,000. We identified 12 cases of HCA among adults with a history of childhood or young adult cancer. The most common cancer diagnosis was leukemia (N = 4). Five had undergone allogeneic hematopoietic stem cell transplant with total body irradiation. All 11 females had prior estrogen therapy; the male case was hypogonadal...
October 26, 2016: Pediatric Blood & Cancer
Yoko Miyoshi, Kie Yasuda, Makiko Tachibana, Hisao Yoshida, Emiko Miyashita, Takako Miyamura, Yoshiko Hashii, Kae Hashimoto, Tadashi Kimura, Keiichi Ozono
Gonadal dysfunction and infertility are major endocrinological late effects among childhood cancer survivors. Chemotherapy and radiation have gonadotoxic effects and diminish the ovarian reserve. The serum concentration of anti-Müllerian hormone (AMH) is a useful marker of ovarian reserve in survivors. We conducted a longitudinal study to investigate the variations of AMH in evaluating the acute and chronic effects of cancer therapy on the ovary. Three young female patients with different hematological diseases were registered, and their medical records were reviewed...
October 2016: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
F Barabé, L Gil, M Celton, A Bergeron, V Lamontagne, É Roques, K Lagacé, A Forest, R Johnson, L Pécheux, J Simard, J Pelloux, A Bellemare-Pelletier, E Gagnon, J Hebert, S Cellot, B T Wilhelm
Acute myeloid leukemias (AML) result from a series of genetic events occurring in a stem or progenitor hematopoietic cell which gives rise to their clonal expansion and an impaired capacity to differentiate. To circumvent the genetic heterogeneity of AML patient cohorts, we have developed a model system, driven by the MLL-AF9 (MA9) oncogene, to generate multiple human leukemias using progenitor cells from a single healthy donor. Through stepwise RNA-sequencing data generated using this model and AML patients, we have identified consistent changes associated with MA9-driven leukemogenesis and demonstrate that no recurrent secondary mutations are required...
October 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nathália Azevedo Portilho, Priscila Tavares Guedes, B Anne Croy, Marcelo Pelajo-Machado
Previous studies have shown that human and mouse placentas have hematopoietic potential during mid-gestation. In this investigation, we used histological and immunohistological approaches to visualize hematopoietic cells in mouse placenta between 9.5 and 12.5 days of gestation (gd), identifying their topography and niche. Putative hematopoietic foci were present on 10.5 and 11.5 gd but not 9.5 or 12.5 gd and was restricted to the placental labyrinth. Two major niches each with distinctive hematopoietic cell clusters were present...
November 2016: Placenta
Wojciech Marlicz, Katarzyna Sielatycka, Karol Serwin, Ewa Kubis, Marta Tkacz, Rafał Głuszko, Andrzej Białek, Teresa Starzyńska, Mariusz Z Ratajczak
Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblast‑like stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma...
October 18, 2016: Oncology Reports
P Huezo-Diaz Curtis, C R S Uppugunduri, J Muthukumaran, M A Rezgui, C Peters, P Bader, M Duval, H Bittencourt, Maja Krajinovic, Marc Ansari
Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.1364 G>T (ORTT=10.6, 95% confidence interval (CI)=2.16, 51.54) and SOS risk, which was sex dependent (female patients, ORTT=21...
October 25, 2016: Pharmacogenomics Journal
M V Barbado, M Medrano, T Caballero-Velázquez, I Álvarez-Laderas, L I Sánchez-Abarca, E García-Guerrero, J Martín-Sánchez, I V Rosado, J I Piruat, P Gonzalez-Naranjo, N E Campillo, J A Páez, J A Pérez-Simón
Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined. Here we have investigated their anti-tumor effect in multiple myeloma (MM). We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells. This effect was mediated by caspase activation, mainly caspase-2, and was partially prevented by a pan-caspase inhibitor...
October 25, 2016: International Journal of Cancer. Journal International du Cancer
Wei Wei, Chao Xu, Zhi-Yong Ye, Xiao-Jun Huang, Jia-En Yuan, Tian-Bao Ma, Han-Biao Lin, Xiu-Qiong Chen
The aim of the present study was to obtain the qualified hematopoietic stem/progenitor cells (HSC/HPC) and human umbilical cord-mesenchymal stem cells (MSC) in vitro in the co-culture system. Cord blood mononuclear cells were separated from umbilical cord blood by Ficoll lymphocyte separation medium, and then CD34(+) HSC was collected by MACS immunomagnetic beads. The selected CD34(+) HSC/HPC and MSC were transferred into culture flask. IMDM culture medium with 15% AB-type cord plasma supplemented with interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), stem cell factor (SCF) and FMS-like tyrosine kinase 3 ligand (Flt-3L) factors were used as the co-culture system for the amplification of HSC/HPC and MSC...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Karin Gustafsson, Michael Welsh
No abstract text is available yet for this article.
2016: Stem Cell Investigation
Takeru Asano, Ken-Ichi Matsuoka, Satoshi Iyama, Kazuteru Ohashi, Yoshihiro Inamoto, Chikako Ohwada, Makoto Murata, Atsushi Satake, Chikamasa Yoshida, Koichi Nakase, Yasuo Mori, Mitsune Yamamoto
Chronic graft versus host disease (cGVHD) remains a major problem for long survivors after allogeneic hematopoietic stem cell transplantation (HSCT). Currently, corticosteroid therapy is effective for cGVHD as the first line therapy. However, prolonged therapy with corticosteroids causes various severe adverse events. To develop the new therapeutic strategy of cGVHD, we have launched a multicenter phase I/IIa clinical trial of low dose subcutaneous interleukin-2 (IL-2) for treatment of steroid refractory cGVHD, which is constituted of 2 sequential phases (induction phase and maitanance phase)...
October 2016: Acta Medica Okayama
Ioannis Politikos, Haesook Kim, Theodoros Karantanos, Julia Brown, Sean McDonough, Lequn Li, Corey Cutler, Joseph H Antin, Karen K Ballen, Jerome Ritz, Vassiliki A Boussiotis
Umbilical cord blood (UCB) is a valuable graft source for allogeneic hematopoietic stem cell transplantation (HSCT) in patients who lack adult donors. UCB transplantation (UCBT) in adults results in delayed immune reconstitution leading to high infection-related morbidity and mortality. Angiogenic factors and markers of endothelial dysfunction have biologic and prognostic significance in conventional HSCT, but their role in UCBT has not been investigated. Furthermore, the interplay between angiogenesis and immune reconstitution has not been studied...
October 21, 2016: Biology of Blood and Marrow Transplantation
Annalisa Ruggeri, Fernanda Volt, Franco Locatelli, Gerard Michel, Cristina Diaz de Heredia, Manuel Abecasis, Marco Zecca, Ajay Vora, Karima Yakouben, Tracey A O'Brien, Stefano Giardino, Jacqueline Cornish, Vanderson Rocha, Christina Peters, Peter Bader, Eliane Gluckman, Jean Hugues Dalle
Infant acute leukemia still has poor prognosis and allogeneic hematopoietic stem cell transplantation is indicated in selected patients. Umbilical cord blood (UCB) is an attractive cell source for this population due to the low risk of chronic graft-versus-host disease (GVHD), the strong graft-versus-leukemia (GVL) effect and prompt donor availability. This is a retrospective, registry-based study reporting umbilical cord blood transplantation (UCBT) outcomes in 252 children with ALL (n=157) or AML (n=95) diagnosed before 1 year of age who received a single-unit UCBT after myeloablative conditioning between 1996 and 2012 in EBMT centers...
October 21, 2016: Biology of Blood and Marrow Transplantation
Takaaki Konuma, Yasushi Miyazaki, Naoyuki Uchida, Kazuteru Ohashi, Tadakazu Kondo, Hirohisa Nakamae, Satoshi Takahashi, Takehiko Mori, Yukiyasu Ozawa, Chiaki Kato, Koji Iwato, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Ken Ishiyama
Trisomy 8 (+8) is one of the most common cytogenetic abnormalities in adult patients with myelodysplastic syndrome (MDS). However, the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients with MDS harboring +8 remains unclear. To evaluate the outcome and prognostic factors in patients with MDS harboring +8 as the sole cytogenetic abnormality or in association with other abnormalities, we retrospectively analyzed the Japanese registration data of 381 adult patients with MDS harboring +8 treated with allogeneic HSCT between 1990 and 2013...
October 21, 2016: Biology of Blood and Marrow Transplantation
Eva de Berranger, Sandie Balcaen, Malika Ainaoui, Caroline Bompoint, Cécile Borel, Nathalie Chevallier, Natacha de Bentzmann, Virginie Denis, Karine Kerautret, Sandrine Godin, Marie-Laure Labat, Maïna Letort-Bertrand, Sophie Porcheron, Leonardo Magro, Ibrahim Yakoub-Agha, Myriam Guiraud
In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. Our article discusses the updates and modifications for the 2016 version of the national patient follow-up care logbook.
October 21, 2016: Bulletin du Cancer
I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
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