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Bone marrow engraftment

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
Serdar Sivgin, Sinan Nazlim, Gokmen Zararsiz, Osman Baspinar, Leylagul Kaynar, Kemal Deniz, Mustafa Cetin, Ali Unal, Bulent Eser
BACKGROUND: Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS: In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n = 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
L Faivre, M Chaussard, L Vercellino, V Vanneaux, B Hosten, K Teixera, V Parietti, P Merlet, L Sarda-Mantel, N Rizzo-Padoin, J Larghero
PURPOSE OF THE STUDY: After transplantation, cord blood (CB) hematopoietic stem and progenitor cells (HSPCs) are able to home to the bone marrow niche and to reconstitute the hematopoietic system. PET-CT imaging may be a useful method to monitor this parameter in different conditions. The aim of our study was to set up an efficient method for HSPC radiolabelling with [(18)F] fluorodeoxyglucose ((18)F-FDG) and to follow early HSPC homing through PET-CT in mice. MATERIALS AND METHODS: Purified CB HSPCs were radiolabelled with (18)F-FDG at 37° C with various conditions of cell concentration, incubation time and radioactivity concentration in order to define the in vitro condition that allows both sufficient (18)F-FDG uptake to get high quality PET imaging, and preservation of HSPC viability and functional properties during 3h after radiolabelling...
July 2016: Current Research in Translational Medicine
Florent Elefteriou
The bone marrow microenvironment is characterized by its multicellular nature, and perhaps less obviously by the high mobility of multiple transient and stationary cell lineages present in this environment. The trafficking of hematopoietic and mesenchymal cells between the bone marrow and blood compartments is regulated by a number of bone marrow-derived factors. It is suspected that transformed metastatic cells "hijack" these processes to engraft into the skeleton and eventually cause the skeletal complications associated with metastatic disease...
September 2016: Journal of Bone Oncology
Omar S Aljitawi, Soumen Paul, Avishek Ganguly, Tara L Lin, Sid Ganguly, George Vielhauer, Maegan L Capitano, Amy Cantelina, Brea Lipe, Jonathan D Mahnken, Amanda Wise, Abigale Berry, Anurag K Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P McGuirk, Hal E Broxmeyer
Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed in order to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34(+) cells...
October 19, 2016: Blood
Ashley I Beyer, Marcus O Muench
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen and liver was evaluated by flow cytometry 12 weeks after transplant...
October 19, 2016: Stem Cells and Development
Takashi Ishida, Sachie Suzuki, Chen-Yi Lai, Satoshi Yamazaki, Shigeru Kakuta, Yoichiro Iwakura, Masanori Nojima, Yasuo Takeuchi, Masaaki Higashihara, Hiromitsu Nakauchi, Makoto Otsu
Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs)...
October 18, 2016: Stem Cells
Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Joseph B Moore, J Zhao, Ahmed Abdel-Latif, Marcin Wysoczynski, Mariusz Z Ratajczak
Nitric oxide (NO) is a gaseous free radical molecule involved in several biological processes related to inflammation, tissue damage, and infections. Based on reports that NO inhibits migration of granulocytes and monocytes, we became interested in the role of inducible NO synthetase (iNOS) in pharmacological mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). To address the role of NO in HSPC trafficking, we upregulated or downregulated iNOS expression in hematopoietic cell lines...
October 17, 2016: Stem Cell Reviews
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
: : Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
October 14, 2016: Stem Cells Translational Medicine
Antonella Antonelli, Willy A Noort, Jenny Jaques, Bauke de Boer, Regina de Jong-Korlaar, Annet Z Brouwers-Vos, Linda Lubbers-Aalders, Jeroen F van Velzen, Andries C Bloem, Huipin Yuan, Joost D de Bruijn, Gert J Ossenkoppele, Anton C M Martens, Edo Vellenga, Richard W J Groen, Jan Jacob Schuringa
In order to begin to understand mechanisms that regulate self-renewal, differentiation and transformation of human hematopoietic stem cells, or to evaluate the efficacy of novel treatment modalities, stem cells need to be studied in their own species-specific microenvironment. By implanting ceramic scaffolds coated with human mesenchymal stromal cells (MSCs) into immune deficient mice we mimic the human bone marrow niche. Thus, we have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted covering all important genetic and risk subgroups...
October 12, 2016: Blood
Oh Young Bang, Eun Hee Kim, Jae Min Cha, Gyeong Joon Moon
Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation...
September 2016: Journal of Stroke
Benedetta Mazzanti, Serena Urbani, Simone Dal Pozzo, Paola Bufano, Lara Ballerini, Alessia Gelli, Irene Sodi, Irene Donnini, Massimo Di Gioia, Stefano Guidi, Julien Camisani, Riccardo Saccardi
BACKGROUND: Clinical grade processing of harvested bone marrow is required in various clinical situations, particularly in the management of ABO mismatching in allogeneic haematopoietic stem cell transplantation (HSCT) and in regenerative medicine. MATERIAL AND METHODS: We report a single-centre experience using a fully automated, clinical grade, closed system (Sepax, Biosafe, Switzerland). From 2003 to 2015, 125 procedures were performed in our laboratory, including buffy-coat production for HSCT (n=58), regenerative medicine in an orthopaedic setting (n=54) and density-gradient separation in a trial for treatment of critical limb ischaemia (n=13)...
September 27, 2016: Blood Transfusion, Trasfusione del Sangue
Hang Zhao, Zhiying He, Dandan Huang, Jun Gao, Yanfang Gong, Hongyu Wu, Aifang Xu, Xiangjun Meng, Zhaoshen Li
Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection...
2016: Stem Cells International
William Nigel Patton, Ian Nivison-Smith, Peter Bardy, Anthony Dodds, David Ma, Peter John Shaw, John Kwan, Leonie Wilcox, Andrew Butler, John M Carter, Hilary Blacklock, Jeffrey Szer
A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and NZ analysed transplant outcomes according to graft transit times. Of evaluable cases (n=233), 76 (33%) grafts were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and NZ (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total)...
October 4, 2016: Biology of Blood and Marrow Transplantation
Marco Saia, Alberto Termanini, Nicoletta Rizzi, Massimiliano Mazza, Elisa Barbieri, Debora Valli, Paolo Ciana, Alicja M Gruszka, Myriam Alcalay
The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice...
October 7, 2016: Scientific Reports
Ibrahim Sammour, Santhosh Somashekar, Jian Huang, Sunil Batlahally, Matthew Breton, Krystalenia Valasaki, Aisha Khan, Shu Wu, Karen C Young
BACKGROUND: Mesenchymal stem cells (MSC) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC. Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown. Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males...
2016: PloS One
Ting Yang, Qiaoxian Lin, Jinhua Ren, Ping Chen, Xiaohong Yuan, Xiaofeng Luo, Tingbo Liu, Jing Zheng, Zhihong Zheng, Xiaoyun Zheng, Xinji Chen, Langhui Zhang, Hao Zheng, Zaisheng Chen, Xueling Hua, Shaohua Le, Jian Li, Zhizhe Chen, Jianda Hu
Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not...
October 1, 2016: Oncotarget
Mateusz Adamiak, Malwina Suszynska, Ahmed Abdel-Latif, Ahmed Abdelbaset-Ismail, Janina Ratajczak, Mariusz Z Ratajczak
Migration and bone marrow (BM) homing of hematopoietic stem progenitor cells (HSPCs) is regulated by several signaling pathways, and here we provide evidence for the involvement in this process of hematopoietic-specific phospholipase C-β2 (PLC-β2). This enzyme is involved in release of intracellular calcium and activation of protein kinase C (PKC). Recently we reported that PLC-β2 promotes mobilization of HSPCs from BM into peripheral blood (PB), and this effect is mediated by the involvement of PLC-β2 in the release of proteolytic enzymes from granulocytes and its role in disintegration of membrane lipid rafts...
October 4, 2016: Stem Cell Reviews
João Paulo M C M Cunha, Gunter Leuckx, Peter Sterkendries, Hannelie Korf, Gabriela Bomfim-Ferreira, Lutgart Overbergh, Bart Vaes, Harry Heimberg, Conny Gysemans, Chantal Mathieu
AIMS/HYPOTHESIS: Hypoxia in the initial days after islet transplantation leads to considerable loss of islet mass and contributes to disappointing outcomes in the clinical setting. The aim of the present study was to investigate whether co-transplantation of human non-endothelial bone marrow-derived multipotent adult progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic growth factors during the initial days after implantation, could improve islet engraftment and survival...
October 4, 2016: Diabetologia
Xiaohu Zheng, Xiaolei Fan, Binqing Fu, Meijuan Zheng, Aimei Zhang, Kai Zhong, Jialai Yan, Rui Sun, Zhigang Tian, Haiming Wei
The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling...
October 3, 2016: Cancer Research
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