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Bone marrow engraftment

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https://www.readbyqxmd.com/read/28420436/autophagy-mediates-the-beneficial-effect-of-hypoxic-preconditioning-on-bone-marrow-mesenchymal-stem-cells-for-the-therapy-of-myocardial-infarction
#1
Zheng Zhang, Chao Yang, Mingzhi Shen, Ming Yang, Zhitao Jin, Liping Ding, Wei Jiang, Junke Yang, Haixu Chen, Feng Cao, Taohong Hu
BACKGROUND: Stem cell therapy has emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the poor viability of transplanted stem cells hampers their therapeutic efficacy. Hypoxic preconditioning (HPC) can effectively promote the survival of stem cells. The aim of this study was to investigate whether HPC improved the functional survival of bone marrow mesenchymal stem cells (BM-MSCs) and increased their cardiac protective effect. METHODS: BM-MSCs, isolated from Tg(Fluc-egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), were preconditioned with HPC (1% O2) for 12 h, 24 h, 36 h, and 48 h, respectively, followed by 24 h of hypoxia and serum deprivation (H/SD) injury...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28408761/endothelial-and-astrocytic-support-by-human-bone-marrow-stem-cell-grafts-into-symptomatic-als-mice-towards-blood-spinal-cord-barrier-repair
#2
Svitlana Garbuzova-Davis, Crupa Kurien, Avery Thomson, Dimitri Falco, Sohaib Ahmad, Joseph Staffetti, George Steiner, Sophia Abraham, Greeshma James, Ajay Mahendrasah, Paul R Sanberg, Cesario V Borlongan
Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28406754/spheroid-coculture-of-hematopoietic-stem-progenitor-cells-and-monolayer-expanded-mesenchymal-stem-stromal-cells-in-polydimethylsiloxane-microwells-modestly-improves-in-vitro-hematopoietic-stem-progenitor-cell-expansion
#3
Kathryn Futrega, Kerry Atkinson, William B Lott, Michael R Doran
While two-dimensional (2D) monolayers of mesenchymal stem/stromal cells (MSCs) have been shown to enhance hematopoietic stem/progenitor cell (HSPC) expansion in vitro, expanded cells do not engraft long term in human recipients. This outcome is attributed to the failure of 2D culture to recapitulate the bone marrow (BM) niche signal milieu. Herein, we evaluated the capacity of a novel three-dimensional (3D) coculture system to support HSPC expansion in vitro. A high-throughput polydimethylsiloxane (PDMS) microwell platform was used to manufacture thousands of uniform 3D multicellular coculture spheroids...
April 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28401745/hypocellular-acute-myeloid-leukemia-treated-with-bone-marrow-transplantation
#4
Dai Keino, Kensuke Kondoh, Ryo Ohyama, Mizuho Morimoto, Tetsuya Mori, Masafumi Ito, Akitoshi Kinoshita
Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and is extremely rare in childhood. There is still no established treatment for hypocellular AML. We report the case of an 11-year-old boy with hypocellular AML who was treated successfully with allogenic bone marrow transplantation (allo-BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration and biopsy confirmed a diagnosis of hypocellular AML. Although low-dose cytarabine induced reduction of blasts, it did not lead to complete remission...
April 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28395110/murine-models-of-transplantation-tolerance-through-mixed-chimerism-advances-and-roadblocks
#5
REVIEW
Benedikt Mahr, Thomas Wekerle
Organ transplantation is the treatment of choice for patients with end-stage organ failure but chronic immunosuppression is taking its toll in terms of morbidity and poor efficacy in preventing late graft loss. Therefore a drug-free state would be desirable where the recipient permanently accepts a donor organ while remaining otherwise fully immunologically competent. Mouse studies unveiled mixed chimerism as an effective approach to deliberately induce such donor-specific tolerance and laid the foundation for a series of clinical pilot trials...
April 10, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28389253/role-of-genetic-polymorphism-of-aldh2-in-hematopoietic-stem-cell-transplantation
#6
Tomotaka Ugai, Yoshinobu Kanda, Yasuo Morishima, Keitaro Matsuo
Aldehyde dehydrogenase 2 (ALDH2) is involved in critically important biological processes, such as the metabolism of aldehydes and aldehyde-induced genotoxicity in hematopoietic stem cells. Given its role in these biological processes, we hypothesized that a functional ALDH2 polymorphism could affect transplant outcome after hematopoietic stem cell transplantation. Here, we analyzed the Japanese national registry data for 409 patients who underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched unrelated donor...
April 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28375987/hematopoietic-stem-cells-under-pressure
#7
Miguel Ganuza, Shannon McKinney-Freeman
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation...
April 1, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28374977/hypoxic-preconditioning-induced-autophagy-enhances-survival-of-engrafted-endothelial-progenitor-cells-in-ischaemic-limb
#8
Pei Zhou, Yu-Zhen Tan, Hai-Jie Wang, Guo-Dong Wang
Recent clinical studies have suggested that endothelial progenitor cells (EPCs) transplantation provides a modest benefit for treatment of the ischaemic diseases such as limb ischaemia. However, cell-based therapies have been limited by poor survival of the engrafted cells. This investigation was designed to establish optimal hypoxia preconditioning and evaluate effects of hypoxic preconditioning-induced autophagy on survival of the engrafted EPCs. Autophagy of CD34(+) VEGFR-2(+) EPCs isolated from rat bone marrow increased after treatment with 1% O2 ...
April 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28374110/htlv-1-infection-and-neuropathogenesis-in-the-context-of-rag1-%C3%AE-c-rag1-hu-and-blt-mice
#9
Rashida Ginwala, Breanna Caruso, Zafar K Khan, Ajinkya Pattekar, Glen M Chew, Michael J Corley, Ronak Loonawat, Steven Jacobson, Sreesha Sreedhar, Lishomwa C Ndhlovu, Pooja Jain
To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1(-/-)γc(-/-) or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34(+) hematopoietic stem cells...
April 4, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28368374/increase-of-bone-marrow-macrophages-and-cd8-t-lymphocytes-predict-graft-failure-after-allogeneic-bone-marrow-or-cord-blood-transplantation
#10
N Kawashima, S Terakura, S Nishiwaki, D Koyama, Y Ozawa, M Ito, K Miyamura
Graft failure (GF) remains an obstacle to survival after allogeneic hematopoietic stem cell transplantation. However, differentiating GF from delayed engraftment (DE) can be difficult. Host CD8(+) lymphocytes have been reported to mediate graft rejection, but the impact of macrophages on DE or GF is yet to be clarified. Peri-engraftment bone marrow (BM) specimens of 32 adult patients with normal engraftment, DE or GF were retrospectively evaluated to identify the potential associations of CD163(+) macrophage and CD8(+) lymphocyte infiltration into BM...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28362378/combining-intravital-fluorescent-microscopy-ivfm-with-genetic-models-to-study-engraftment-dynamics-of-hematopoietic-cells-to-bone-marrow-niches
#11
Lin Wang, Malgorzata M Kamocka, Amy Zollman, Nadia Carlesso
Increasing evidence indicates that normal hematopoiesis is regulated by distinct microenvironmental cues in the BM, which include specialized cellular niches modulating critical hematopoietic stem cell (HSC) functions(1)(,)(2). Indeed, a more detailed picture of the hematopoietic microenvironment is now emerging, in which the endosteal and the endothelial niches form functional units for the regulation of normal HSC and their progeny(3)(,)(4)(,)(5). New studies have revealed the importance of perivascular cells, adipocytes and neuronal cells in maintaining and regulating HSC function(6)(,)(7)(,)(8)...
March 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28358858/a-preclinical-evaluation-of-alternative-site-for-islet-allotransplantation
#12
Chengshi Wang, Xiaojiong Du, Sirong He, Yujia Yuan, Pengfei Han, Dan Wang, Younan Chen, Jingping Liu, Bole Tian, Guang Yang, Shounan Yi, Fabao Gao, Zhihui Zhong, Hongxia Li, Jingqiu Cheng, Yanrong Lu
The bone marrow cavity (BMC) has recently been identified as an alternative site to the liver for islet transplantation. This study aimed to compare the BMC with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant)...
2017: PloS One
https://www.readbyqxmd.com/read/28358695/induction-of-tgf-%C3%AE-by-irradiation-or-chemotherapy-in-fanconi-anemia-fa-mouse-bone-marrow-is-modulated-by-small-molecule-radiation-mitigators-jp4-039-and-mms350
#13
Michael W Epperly, Byung-Han Rhieu, Darcy Franicola, Tracy Dixon, Shaonan Cao, Xichen Zhang, Donna Shields, Hong Wang, Peter Wipf, Joel S Greenberger
BACKGROUND/AIM: Total-body irradiation and/or administration of chemotherapy drugs in bone marrow transplantation induce cytokines that can suppress engraftment. Fanconi Anemia (FA) patients have a hyperactive responsiveness to the inhibitory cytokine, transforming growth factor-beta (TGF-β). Small molecule radiation mitigator drugs, JP4-039 and MMS350, were evaluated for suppression of irradiation or drug-induced TGF-β. MATERIALS AND METHODS: In vivo induction of TGF-β by total-body ionizing irradiation (TBI), L-phenylalanine mustard (L-PAM), busulfan or fludarabine, was quantified...
March 2017: In Vivo
https://www.readbyqxmd.com/read/28355300/evaluation-of-synthetic-vascular-grafts-in-a-mouse-carotid-grafting-model
#14
Alex H P Chan, Richard P Tan, Praveesuda L Michael, Bob S L Lee, Laura Z Vanags, Martin K C Ng, Christina A Bursill, Steven G Wise
Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses...
2017: PloS One
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-non-myeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#15
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Non-myeloablative conditioning using total lymphoid irradiation (TLI) and rabbit anti-thymocyte serum (ATS) (the murine pre-clinical equivalent of anti-thymocyte globulin/ATG) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for non-malignant disorders. We previously reported that donor effector T cell function and GVHD are regulated via recipient invariant natural killer T cell (iNKT cell) IL-4-driven expansion of donor Foxp3(+) naturally occurring Treg...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28346415/haplo-cord-transplantation-compared-to-haploidentical-transplantation-with-post-transplant-cyclophosphamide-in-patients-with-aml
#16
M Kwon, G Bautista, P Balsalobre, I Sánchez-Ortega, P Montesinos, A Bermúdez, A de Laiglesia, P Herrera, C Martin, K Humala, A Zabalza, M Torres, L Bento, L L Corral, I Heras, D Serrano, I Buño, J Anguita, C Regidor, R Duarte, R Cabrera, J Gayoso, J L Diez-Martin
For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28345002/cxcl12-promotes-stem-cell-recruitment-and-uterine-repair-after-injury-in-asherman-s-syndrome
#17
Gulcin Sahin Ersoy, Masoumeh Majidi Zolbin, Emine Cosar, Irene Moridi, Ramanaiah Mamillapalli, Hugh S Taylor
Asherman's syndrome is an acquired condition of uterine fibrosis and adhesions in response to injury that adversely affects fertility and pregnancy. We have previously demonstrated that bone marrow-derived mesenchymal stem cells (BMDSCs) contribute to uterine repair after injury and that stem cells supplementation improves fertility. Here, we demonstrate that CXCL12 is the chemokine that mediates stem cell engraftment and functional improvement using a murine model of Asherman's syndrome. After uterine injury, we demonstrate that CXCL12 augmentation increased BMDSC engraftment and that the CXCL12 receptor (CXCR4) antagonist, ADM3100, blocked stem cell recruitment...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344999/long-term-engraftment-and-fetal-globin-induction-upon-bcl11a-gene-editing-in-bone-marrow-derived-cd34-hematopoietic-stem-and-progenitor-cells
#18
Kai-Hsin Chang, Sarah E Smith, Timothy Sullivan, Kai Chen, Qianhe Zhou, Jason A West, Mei Liu, Yingchun Liu, Benjamin F Vieira, Chao Sun, Vu P Hong, Mingxuan Zhang, Xiao Yang, Andreas Reik, Fyodor D Urnov, Edward J Rebar, Michael C Holmes, Olivier Danos, Haiyan Jiang, Siyuan Tan
To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the BCL11A gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34(+) hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of BCL11A resulting from bi-allelic frameshift mutations in BCL11A exon 2 adversely affected erythroid enucleation...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344987/safe-and-effective-gene-therapy-for-murine-wiskott-aldrich-syndrome-using-an-insulated-lentiviral-vector
#19
Swati Singh, Iram Khan, Socheath Khim, Brenda Seymour, Karen Sommer, Matthew Wielgosz, Zachary Norgaard, Hans-Peter Kiem, Jennifer Adair, Denny Liggitt, Arthur Nienhuis, David J Rawlings
Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344885/pappalysin-1-t-cell-receptor-transgenic-allo-restricted-t-cells-kill-ewing-sarcoma-in-vitro-and-in-vivo
#20
Andreas Kirschner, Melanie Thiede, Thomas G P Grünewald, Rebeca Alba Rubio, Günther H S Richter, Thomas Kirchner, Dirk H Busch, Stefan Burdach, Uwe Thiel
Pregnancy-associated plasma protein-A (PAPPA), also known as pappalysin, is a member of the insulin-like growth factor (IGF) family. PAPPA acts as a protease, cleaving IGF inhibitors, i.e., IGF binding proteins (IGFBPs), thereby setting free IGFs. The insulin/IGF-axis is involved in cancer in general and in Ewing sarcoma (ES) in particular. ES is a highly malignant bone tumor characterized by early metastatic spread. PAPPA is associated with various cancers. It is overexpressed and required for proliferation in ES...
2017: Oncoimmunology
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