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https://www.readbyqxmd.com/read/28813430/reprogramming-human-gallbladder-cells-into-insulin-producing-%C3%AE-like-cells
#1
Feorillo Galivo, Eric Benedetti, Yuhan Wang, Carl Pelz, Jonathan Schug, Klaus H Kaestner, Markus Grompe
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#2
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810165/human-immune-system-mouse-models-of-ebola-virus-infection
#3
REVIEW
Jessica R Spengler, Joseph Prescott, Heinz Feldmann, Christina F Spiropoulou
Human immune system (HIS) mice, immunodeficient mice engrafted with human cells (with or without donor-matched tissue), offer a unique opportunity to study pathogens that cause disease predominantly or exclusively in humans. Several HIS mouse models have recently been used to study Ebola virus (EBOV) infection and disease. The results of these studies are encouraging and support further development and use of these models in Ebola research. HIS mice provide a small animal model to study EBOV isolates, investigate early viral interactions with human immune cells, screen vaccines and therapeutics that modulate the immune system, and investigate sequelae in survivors...
August 11, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28809828/bioengineering-of-humanized-bone-marrow-microenvironments-in-mouse-and-their-visualization-by-live-imaging
#4
Diana Passaro, Ander Abarrategi, Katie Foster, Linda Ariza-McNaughton, Dominique Bonnet
Human hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche, an intricate, multifactorial network of components producing cytokines, growth factors, and extracellular matrix. The ability of HSCs to remain quiescent, self-renew or differentiate, and acquire mutations and become malignant depends upon the complex interactions they establish with different stromal components. To observe the crosstalk between human HSCs and the human BM niche in physiological and pathological conditions, we designed a protocol to ectopically model and image a humanized BM niche in immunodeficient mice...
August 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28807057/inhibitory-effects-of-hnf4%C3%AE-on-migration-maltransformation-of-hepatic-progenitors-hnf4%C3%AE-overexpressing-hepatic-progenitors-for-liver-repopulation
#5
Ping Wang, Min Cong, Tianhui Liu, Hufeng Xu, Lin Wang, Guangyong Sun, Aiting Yang, Dong Zhang, Jian Huang, Yameng Sun, Wenshan Zhao, Hong Ma, Jidong Jia, Hong You
BACKGROUND: Although they are expandable in vitro, hepatic progenitors are immature cells and share many immunomarkers with hepatocellular carcinoma, raising potential concerns regarding maltransformation after transplantation. This study investigated the effects of hepatic nuclear factor (HNF) 4α on the proliferation, migration, and maltransformation of hepatic progenitors and determined the feasibility of using these manipulated cells for transplantation. METHODS: The effects of HNF4α on rat hepatic progenitors (i...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#6
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28806855/functional-stem-cell-integration-into-neural-networks-assessed-by-organotypic-slice-cultures
#7
David Forsberg, Charoensri Thonabulsombat, Johan Jäderstad, Linda Maria Jäderstad, Petri Olivius, Eric Herlenius
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host...
August 14, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28803829/the-vascular-niche-regulates-hematopoietic-stem-and-progenitor-cell-lodgment-and-expansion-via-klf6a-ccl25b
#8
Yuanyuan Xue, Junhua Lv, Chunxia Zhang, Lu Wang, Dongyuan Ma, Feng Liu
In mammals, hematopoietic stem and progenitor cells (HSPCs) rapidly expand in the fetal liver (FL), but the underlying mechanism remains unclear. Here, we characterize zebrafish caudal hematopoietic tissue (CHT) and identify an important cellular and molecular mechanism of HSPC expansion. Time-lapse imaging showed that HSPCs localize adjacent to vascular endothelial cells (ECs), and their migration and expansion display caudal vein-specific orientation in the CHT. RNA sequencing and functional analysis identified that an EC-expressed transcription factor, Krüppel-like factor 6a (Klf6a), is essential for the CHT niche...
August 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28802588/t-cell-costimulation-blockade-promotes-transplantation-tolerance-in-combination-with-sirolimus-and-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-in-children-with-severe-aplastic-anemia
#9
Sarita Rani Jaiswal, Prakash Bhakuni, Shamsuz Zaman, Satish Bansal, Priyanka Bharadwaj, Sneh Bhargava, Suparno Chakrabarti
We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28801972/brief-report-a-differential-transcriptomic-profile-of-ex-vivo-expanded-adult-human-hematopoietic-stem-cells-empowers-them-for-engraftment-better-than-their-surface-phenotype
#10
Nikoletta Psatha, Grigorios Georgolopoulos, Susan Phelps, Thalia Papayannopoulou
Transplantation of small cord blood (CB) units, or of autologous ex vivo-genetically modified adult hematopoietic stem cells (HSC), face the common challenge of suboptimal HSC doses for infusion and impaired engraftment of the transplanted cells. Ex vivo expansion of HSCs, using either cell-based coculture approaches or especially small molecules have been successfully tested mainly in CB and in prolonged cultures. Here, we explored whether innovative combinations of small molecules can sufficiently, after short culture, expand adult HSCs while retaining their functionality in vivo...
August 11, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28801891/monitoring-of-busulphan-concentrations-in-children-undergone-hematopoietic-stem-cell-transplantation-unicentric-experience-over-10%C3%A2-years
#11
Maura Faraci, Carmine Tinelli, Edoardo Lanino, Stefano Giardino, Massimiliano Leoni, Marta Ferretti, Elio Castagnola, Monica Broglia, Annalisa De Silvestri, Daniela Di Martino, Antonella Bartoli
BACKGROUND AND OBJECTIVES: The aim of this report is to describe the experience in the management of busulphan-based conditioning regimen administered before hematopoietic stem cell transplantation (HSCT) in children. METHODS: We report the values of the first dose AUC (area under the concentration-time curve, normal target between 3600 and 4800 ng·h/mL) in children treated with oral and intravenous busulphan, and we analyze the impact of some clinical variables in this cohort of patients...
August 11, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28801449/engraftment-and-in-vivo-proliferation-advantage-of-gene-corrected-mobilized-cd34-cells-from-fanconi-anemia-patients
#12
Paula Río, Susana Navarro, Guillermo Guenechea, Rebeca Sánchez-Domínguez, Maria Luisa Lamana, Rosa Yañez, Jose A Casado, Parinda A Mehta, Maria Roser Pujol, Jordi Surrallés, Sabine Charrier, Anne Galy, José C Segovia, Cristina Díaz de Heredia, Julián Sevilla, Juan Bueren
Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene corrected hematopoietic stem and progenitor cells (HSPC) from FA patients, either after autologous transplantation or infusion into immunodeficient mice. In this study we demonstrate that a validated short transduction protocol of G-CSF plus plerixafor-mobilized CD34(+) cells from FA-A patients with a therapeutic FANCA-lentiviral vector corrects the phenotype of in vitro cultured hematopoietic progenitor cells. Transplantation of transduced FA CD34(+) cells into immunodeficient mice resulted in reproducible engraftment of myeloid, lymphoid and CD34(+) cells...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28800845/assessment-of-stability-of-cd34-cell-products-enriched-by-immunoselection-from-peripheral-blood-mononuclear-cells-during-refrigerated-storage
#13
Metka Krasna, Elvira Malicev, Jasmina Ziva Rozman, Bojan Vrtovec
Durable engraftment of transplanted CD34+ cells largely depends on the quality of the cell product. Limited data are currently available about extended storage of immunoselected CD34+ cells. The aim of our study was to assess the stability of CD34+ cell product with the cells stored in high concentration (80×10(6) in 6mL) in small bags intended for cell implantation. Cell products were prepared by leukapheresis and immunoselection (Clinimacs(plus) procedure) from 13 patients with chronic dilated cardiomyopathy...
July 22, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28800741/erythrocyte-depletion-from-bone-marrow-performance-evaluation-after-50-clinical-scale-depletions-with-spectra-optia-bmc
#14
Soo-Zin Kim-Wanner, Gesine Bug, Juliane Steinmann, Salem Ajib, Nadine Sorg, Carolin Poppe, Milica Bunos, Eva Wingenfeld, Christiane Hümmer, Beate Luxembourg, Erhard Seifried, Halvard Bonig
BACKGROUND: Red blood cell (RBC) depletion is a standard graft manipulation technique for ABO-incompatible bone marrow (BM) transplants. The BM processing module for Spectra Optia, "BMC", was previously introduced. We here report the largest series to date of routine quality data after performing 50 clinical-scale RBC-depletions. METHODS: Fifty successive RBC-depletions from autologous (n = 5) and allogeneic (n = 45) BM transplants were performed with the Spectra Optia BMC apheresis suite...
August 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28798321/crispr-cas9-mediated-deletion-of-foxn1-in-nod-scid-il2rg-mice-results-in-severe-immunodeficiency
#15
Xinru Wei, Yunxin Lai, Baiheng Li, Le Qin, Youdi Xu, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Guohua Huang, Qiuhua Deng, Pentao Liu, Donghai Wu, Liangxue Lai, Yao Yao, Peng Li
Immunodeficient mice engrafted with either normal or cancerous human cells are widely used in basic and translational research. In particular, NOD/SCID/IL2rg(-/-) mice can support the growth of various types of human cancer cells. However, the hairs of these mice interfere with the observation and imaging of engrafted tissues. Therefore, novel hairless strains exhibiting comparable immunodeficiency would be beneficial. Recently, the CRISPR/Cas9 system has been used for efficient multiplexed genome editing. In the present study, we generated a novel strain of nude NOD/SCID/IL2rg(-/-) (NSIN) mice by knocking out Foxn1 from NOD/SCID/IL2rg(-/-) (NSI) mice using the CRISPR/Cas9 system...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797783/results-of-prospective-randomized-open-label-non-inferiority-study-of-tbo-filgrastim-granix-%C3%A2-versus-filgrastim-neupogen-%C3%A2-in-combination-with-plerixafor-for-autologous-stem-cell-mobilization-in-patients-with-multiple-myeloma-or-non-hodgkin-lymphoma
#16
Pavan Kumar Bhamidipati, Mark A Fiala, Brenda J Grossman, John F DiPersio, Keith Stokerl-Goldstein, Feng Gao, Geoffrey L Uy, Peter Westervelt, Mark A Schroeder, Amanda F Cashen, Camille N Abboud, Ravi Vij
Autologous hematopoietic stem cell transplantation (Auto- HSCT) improves survival in multiple myeloma (MM) and Non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen® - recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, recombinant G-CSF biosimilar (Tevagrastim®) is approved for various indications similar to reference filgrastim, including stem cell mobilization for auto-HSCT; However, tbo- Filgrastim (Granix®) is registered under original biologic application and is not approved for stem cell mobilization in the USA...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28795658/double-vs-single-cord-blood-transplantation-in-adolescent-and-adult-hematological-malignancies-with-heavier-body-weight-%C3%A2-50%C3%A2-kg
#17
Chang-Cheng Zheng, Xiao-Yu Zhu, Bao-Lin Tang, Xu-Han Zhang, Lei Zhang, Liang-Quan Geng, Hui-Lan Liu, Zi-Min Sun
BACKGROUND: Double-unit cord blood transplantation (CBT) can be used to overcome the limitation of single-unit CBT with low cell content for adults and larger adolescents. However, whether double-unit CBT is superior to single-unit CBT remains controversial. METHODS: We reviewed the medical records of 228 consecutive hematological malignancies who received CBT between November 2005 and December 2013. Ninety-seven eligible patients met the criteria (age ≥14 years and body weight ≥50kg) and were enrolled in this study...
August 10, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28795138/retransplantation-in-late-hepatic-artery-thrombosis-graft-access-and-transplant-outcome
#18
Bettina M Buchholz, Shakeeb Khan, Miruna D David, Bridget K Gunson, John R Isaac, Keith J Roberts, Paolo Muiesan, Darius F Mirza, Dhiraj Tripathi, M Thamara P R Perera
BACKGROUND: Definitive treatment for late hepatic artery thrombosis (L-HAT) is retransplantation (re-LT); however, the L-HAT-associated disease burden is poorly represented in allocation models. METHODS: Graft access and transplant outcome of the re-LT experience between 2005 and 2016 was reviewed with specific focus on the L-HAT cohort in this single-center retrospective study. RESULTS: Ninety-nine (5.7%) of 1725 liver transplantations were re-LT with HAT as the main indication (n = 43; 43%) distributed into early (n = 25) and late (n = 18) episodes...
August 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28793270/pancreatic-islet-blood-flow-dynamics-in-primates
#19
Juan A Diez, Rafael Arrojo E Drigo, Xiaofeng Zheng, Olga V Stelmashenko, Minni Chua, Rayner Rodriguez-Diaz, Masahiro Fukuda, Martin Köhler, Ingo Leibiger, Sai Bo Bo Tun, Yusuf Ali, George J Augustine, Veluchamy A Barathi, Per-Olof Berggren
Blood flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the pancreas. Blood flow velocity in the engrafted islets was not affected by increasing blood glucose levels and/or the GLP-1R agonist liraglutide...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28793244/rho-associated-kinases-and-non-muscle-myosin-iis-inhibit-the-differentiation-of-human-ipscs-to-pancreatic-endoderm
#20
Taro Toyoda, Azuma Kimura, Hiromi Tanaka, Tomonaga Ameku, Atsushi Mima, Yurie Hirose, Masahiro Nakamura, Akira Watanabe, Kenji Osafune
There has been increasing success with the generation of pancreatic cells from human induced pluripotent stem cells (hiPSCs); however, the molecular mechanisms of the differentiation remain elusive. The purpose of this study was to reveal novel molecular mechanisms for differentiation to PDX1(+)NKX6.1(+) pancreatic endoderm cells, which are pancreatic committed progenitor cells. PDX1(+) posterior foregut cells differentiated from hiPSCs failed to differentiate into pancreatic endoderm cells at low cell density, but Rho-associated kinase (ROCK) or non-muscle myosin II (NM II) inhibitors rescued the differentiation potential...
August 8, 2017: Stem Cell Reports
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