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Xenotransplantation

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https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#1
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625053/annotation-of-the-domestic-pig-genome-by-quantitative-proteogenomics
#2
Harald Marx, Hannes Hahne, Susanne E Ulbrich, Angelika Schnieke, Oswald Rottmann, Dimitrij Frishman, Bernhard Kuster
The pig is one of the earliest domesticated animals in the history of human civilization and represents one of the most important livestock animals. The recent sequencing of the Sus scrofa genome was a major step towards the comprehensive understanding of porcine biology, evolution and its utility as a promising large animal model for biomedical and xenotransplantation research. However, the functional and structural annotation of the Sus scrofa genome is far from complete. Here, we present mass spectrometry-based quantitative proteomics data of nine juvenile organs and six embryonic stages between 18 to 39 days after gestation...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28623861/level-of-acceptance-of-islet-cell-and-kidney-xenotransplants-by-personnel-of-hospitals-with-and-without-experience-in-clinical-xenotransplantation
#3
Adrian Abalovich, Shinichi Matsumoto, Carlos J Wechsler, Mariana E Carulla, Martín E Siciliano, Daniel Sznaider, Joachim Denner, Robert B Elliott
BACKGROUND: Recently, significant progress in both safety and efficacy has been achieved in the field of xenotransplantation, as exemplified by results from the first clinical trials of porcine islet transplantation. It would be of interest to learn whether the attitude of the clinical staff involved in such trials changes as the trials are carried out in their own hospital. METHODS: One hundred and four clinical staff members from the Eva Peron Hospital of San Martin (Buenos Aires, Argentina) where clinical trials of islet xenotransplantation have been performed and 92 similar staff members from the Diego Thompson Hospital (Buenos Aires, Argentina) where no such xenotransplantation has been carried out participated in the study...
June 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28618139/large-scale-ex-vivo-generation-of-human-red-blood-cells-from-cord-blood-cd34-cells
#4
Yu Zhang, Chen Wang, Lan Wang, Bin Shen, Xin Guan, Jing Tian, Zhihua Ren, Xinxin Ding, Yupo Ma, Wei Dai, Yongping Jiang
The ex vivo generation of human red blood cells on a large scale from hematopoietic stem and progenitor cells has been considered as a potential method to overcome blood supply shortages. Here, we report that functional human erythrocytes can be efficiently produced from cord blood (CB) CD34(+) cells using a bottle turning device culture system. Safety and efficiency studies were performed in murine and nonhuman primate (NHP) models. With the selected optimized culture conditions, one human CB CD34(+) cell could be induced ex vivo to produce up to 200 million erythrocytes with a purity of 90...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28616498/xenotransplantation-a-special-case-of-one-health
#5
REVIEW
Joachim Denner
The chronic shortage of human transplants to treat tissue and organ failure has led to the development of xenotransplantation, the transplantation of cells, tissues and organs from another species to human recipients. For a number of reasons, pigs are best suited as donor animals. Successful, routine xenotransplantation would have an enormous impact on the health of the human population, including the young, who sometimes require a replacement organ or islet cells, but especially the elderly, who more often suffer the consequences of organ failure...
June 2017: One Health
https://www.readbyqxmd.com/read/28603745/lentivector-iterations-and-pre-clinical-scale-up-toxicity-testing-targeting-mobilized-cd34-cells-for-correction-of-fabry-disease
#6
Ju Huang, Aneal Khan, Bryan C Au, Dwayne L Barber, Lucía López-Vásquez, Nicole L Prokopishyn, Michel Boutin, Michael Rothe, Jack W Rip, Mona Abaoui, Murtaza S Nagree, Shaalee Dworski, Axel Schambach, Armand Keating, Michael L West, John Klassen, Patricia V Turner, Sandra Sirrs, C Anthony Rupar, Christiane Auray-Blais, Ronan Foley, Jeffrey A Medin
Fabry disease is a rare lysosomal storage disorder (LSD). We designed multiple recombinant lentivirus vectors (LVs) and tested their ability to engineer expression of human α-galactosidase A (α-gal A) in transduced Fabry patient CD34(+) hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28593725/xenotransplantation-literature-update-march-april-2017
#7
Eric M Walters, Sheida Etehad Asnaf, Christopher Burlak
No abstract text is available yet for this article.
May 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28591750/mir-346-suppresses-cell-proliferation-through-smyd3-dependent-approach-in-hepatocellular-carcinoma
#8
Weiyou Zhu, Jing Qian, Ling Ma, Pei Ma, Fengming Yang, Yongqian Shu
BACKGROUND & AIMS: The miRNAs are demonstrated to be involved in the carcinogenesis of hepatocellular carcinoma (HCC) and some exhibit potential value for oncotherapy. This study was designed to explore the role of miR-346 in the pathogenesis of hepatocellular carcinoma. METHODS: High throughput screening was employed following with Real time-PCR to investigate the candidate miRNAs. 5-ethynyl-2-deoxyuridine (EdU) assay, CCK-8, transwell assay, cell cycle assay, luciferase reporter assay, western blot and mice xenotransplantation model were performed in the present study...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28579394/primate-primordial-germ-cells-acquire-transplantation-potential-by-carnegie-stage-23
#9
Amander T Clark, Sofia Gkountela, Di Chen, Wanlu Liu, Enrique Sosa, Meena Sukhwani, Jon D Hennebold, Kyle E Orwig
Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice...
May 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28576879/robust-patient-derived-xenografts-of-mds-mpn-overlap-syndromes-capture-the-unique-characteristics-of-cmml-and-jmml
#10
Akihide Yoshimi, Maria E Balasis, Alexis Vedder, Kira Feldman, Yan Ma, Hailing Zhang, Stanley Chun-Wei Lee, Christopher Letson, Sandrine Niyongere, Sydney X Lu, Markus Ball, Justin Taylor, Qing Zhang, Yulong Zhao, Salma Youssef, Young Rock Chung, Xiao Jing Zhang, Benjamin H Durham, Wendy Yang, Alan F List, Mignon L Loh, Virginia Klimek, Michael F Berger, Elliot Stieglitz, Eric Padron, Omar Abdel-Wahab
Chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) are characterized by monocytosis, myelodysplasia, and a characteristic hypersensitivity to GM-CSF. Currently, there are no available disease-modifying therapies for CMML, nor are there preclinical models that fully recapitulate the unique features of CMML. Through use of immunocompromised mice with transgenic expression of human GM-CSF, IL-3, and SCF in a NOD/SCID-IL2Rγ(null) background (NSGS mice), we demonstrate remarkable engraftment of CMML and JMML providing the first examples of serially transplantable and genetically accurate models of CMML...
June 2, 2017: Blood
https://www.readbyqxmd.com/read/28574813/an-immunocompetent-mouse-model-of-human-glioblastoma
#11
Samantha Semenkow, Shen Li, Ulf D Kahlert, Eric H Raabe, Jiadi Xu, Antje Arnold, Miroslaw Janowski, Byoung Chol Oh, Gerald Brandacher, Jeff W M Bulte, Charles G Eberhart, Piotr Walczak
Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant drawback. We present a method of efficient human glioblastoma (GBM) cell engraftment in adult mice with intact immune systems, mediated by a transient blockade of T-cell co-stimulation. Compared to transplants grown in immunodeficient hosts, the resulting tumors more accurately resemble the clinical pathophysiology of patient GBMs, which are characterized by blood-brain-barrier leakage and strong neo-vascularization...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566492/functional-evidence-for-derivation-of-systemic-histiocytic-neoplasms-from-hematopoietic-stem-progenitor-cells
#12
Benjamin H Durham, Damien Roos-Weil, Claude Baillou, Fleur Cohen-Aubart, Akihide Yoshimi, Makoto Miyara, Matthias Papo, Zofia Hélias-Rodzewicz, Nathalie Terrones, Neval Ozkaya, Ahmet Dogan, Raajit Rampal, Fanny Urbain, Lucie Le Fèvre, Eli L Diamond, Christopher Y Park, Thomas Papo, Frédéric Charlotte, Guy Gorochov, Valérie Taly, Olivier A Bernard, Zahir Amoura, Omar Abdel-Wahab, François M Lemoine, Julien Haroche, Jean-Francois Emile
Langerhans Cell Histiocytosis (LCH) and the non-LCH neoplasm Erdheim-Chester Disease (ECD) are heterogeneous neoplastic disorders marked by infiltration of pathologic macrophage-, dendritic cell-, or monocyte-derived cells in tissues driven by recurrent mutations activating MAP kinase signaling. Although recent data indicate that at least a proportion of LCH and ECD patients have detectable activating kinase mutations in circulating hematopoietic cells and bone marrow-based hematopoietic progenitors, functional evidence of the cell-of-origin of histiocytosis from actual patient materials has long been elusive...
May 31, 2017: Blood
https://www.readbyqxmd.com/read/28562356/suppression-of-mir-16-promotes-tumor-growth-and-metastasis-through-reversely-regulating-yap1-in-human-cholangiocarcinoma
#13
Sheng Han, Dong Wang, Guohua Tang, Xinxiang Yang, Chenyu Jiao, Renjie Yang, Yaodong Zhang, Liqun Huo, Zicheng Shao, Zefa Lu, Jiawei Zhang, Xiangcheng Li
BACKGROUND & AIMS: Aberrant expression of microRNAs is associated with many cancers progression. Many studies have shown that miR-16 is down-regulated in many cancers. However, its role in cholangiocarcinoma (CCA) is unknown. METHODS: Quantitative real-time PCR (qRT-PCR) was developed to measure miR-16 expression in CCA tissues and cell lines. CCK-8, colony formation and transwell assays were used to reveal the role of miR-16 in CCA cell proliferation and malignant transformation in vitro...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28553699/generation-of-cmahko-gtko-shtnfri-fc-ho-1-quadruple-gene-modified-pigs
#14
Geon A Kim, Eun Mi Lee, Jun-Xue Jin, Sanghoon Lee, Anukul Taweechaipaisankul, Jong Ik Hwang, Zahid Alam, Curie Ahn, Byeong Chun Lee
As an alternative source of organs for transplantation into humans, attention has been directed to pigs due to their similarities in biological features and organ size. However, severe immune rejection has prevented successful xenotransplantation using pig organs and tissues. To overcome immune rejection, recently developed genetic engineering systems such as TALEN coupled with somatic cell nuclear transfer (SCNT) to make embryos could be used to produce pigs compatible with xenotransplantation. We used the TALEN system to target the non-Gal antigen cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene in pigs that is naturally deleted in humans...
May 28, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28550913/efficient-generation-of-targeted-and-controlled-mutational-events-in-porcine-cells-using-nuclease-directed-homologous-recombination
#15
James R Butler, Rafael M N Santos, Gregory R Martens, Joseph M Ladowski, Zheng-Yu Wang, Ping Li, Matthew Tector, A Joseph Tector
BACKGROUND: Nuclease-based genome editing has rapidly sped the creation of new models of human disease. These techniques also hold great promise for the future of clinical xenotransplantation and cell-based therapies for cancer or immunodeficient pathology. However, to fully realize the potential of nuclease editing tools, the efficiency and precision of their application must be optimized. The object of this study was to use nonintegrating selection and nuclease-directed homologous recombination to efficiently control the genetic modification of the porcine genome...
May 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28536458/epigenetic-priming-restores-the-hla-class-i-antigen-processing-machinery-expression-in-merkel-cell-carcinoma
#16
Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, Jürgen C Becker
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526679/succession-of-transiently-active-tumor-initiating-cell-clones-in-human-pancreatic-cancer-xenografts
#17
Claudia R Ball, Felix Oppel, Karl Roland Ehrenberg, Taronish D Dubash, Sebastian M Dieter, Christopher M Hoffmann, Ulrich Abel, Friederike Herbst, Moritz Koch, Jens Werner, Frank Bergmann, Naveed Ishaque, Manfred Schmidt, Christof von Kalle, Claudia Scholl, Stefan Fröhling, Benedikt Brors, Wilko Weichert, Jürgen Weitz, Hanno Glimm
Although tumor-initiating cell (TIC) self-renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long-term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations...
May 19, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28503733/long-term-safety-from-transmission-of-porcine-endogenous-retrovirus-after-pig-to-non-human-primate-corneal-transplantation
#18
Hyuk Jin Choi, Jiyeon Kim, Jae Young Kim, Hyun Ju Lee, Won Ryang Wee, Mee Kum Kim, Eung Soo Hwang
BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. Accordingly, an investigation was performed to analyze the infectivity of PERVs from porcine keratocytes to human cells, and the long-term risk of transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal transplantation models...
May 14, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28503569/postneonatal-mortality-and-liver-changes-in-cloned-pigs-associated-with-human-tumor-necrosis-factor-receptor-i-fc-and-human-heme-oxygenase-1-overexpression
#19
Geon A Kim, Jun-Xue Jin, Sanghoon Lee, Anukul Taweechaipaisankul, Hyun Ju Oh, Joing-Ik Hwang, Curie Ahn, Islam M Saadeldin, Byeong Chun Lee
Soluble human tumor necrosis factor (shTNFRI-Fc) and human heme oxygenase 1 (hHO-1) are key regulators for protection against oxidative and inflammatory injury for xenotransplantation. Somatic cells with more than 10 copy numbers of shTNFRI-Fc and hHO-1 were employed in somatic cell nuclear transfer to generate cloned pigs, thereby resulting in seven cloned piglets. However, produced piglets were all dead within 24 hours after birth. Obviously, postnatal death with liver apoptosis was reported in the higher copy number of shTNFRI-Fc and hHO-1 piglets...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28492724/human-islet-xenotransplantation-in-rodents-a-literature-review-of-experimental-model-trends
#20
Leandro Ryuchi Iuamoto, André Silva Franco, Fábio Yuji Suguita, Felipe Futema Essu, Lucas Torres Oliveira, Juliana Mika Kato, Matheus Belloni Torsani, Alberto Meyer, Wellington Andraus, Eleazar Chaib, Luiz Augusto Carneiro D'Albuquerque
Among the innovations for the treatment of type 1 diabetes, islet transplantation is a less invasive method of treatment, although it is still in development. One of the greatest barriers to this technique is the low number of pancreas donors and the low number of pancreases that are available for transplantation. Rodent models have been chosen in most studies of islet rejection and type 1 diabetes prevention to evaluate the quality and function of isolated human islets and to identify alternative solutions to the problem of islet scarcity...
April 2017: Clinics
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