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Xenotransplantation

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https://www.readbyqxmd.com/read/28322428/xenotransplantation-where-do-we-stand-in-2016
#1
Gisella L Puga Yung, Robert Rieben, Leo Bühler, Henk-Jan Schuurman, Jörg Seebach
Worldwide, there is a constant rise in the number of patients with end-stage organ failure in critical need for transplants, but the number of organs/cells available from deceased or living human donors is limited. Xenotransplantation using pig organs/tissues repre-sents a potential solution for this shortage; however, it has been hampered by a number of mainly immuno-logical hurdles. Remarkable progress was presented at the latest biennial (13th) international congress of the International Xenotransplantation Association, November 2015 in Melbourne, Australia, and the American Transplant Congress, May 2016 in Boston, USA...
March 21, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28315433/increased-semaphorin-3c-expression-promotes-tumor-growth-and-metastasis-in-pancreatic-ductal-adenocarcinoma-by-activating-the-erk1-2-signaling-pathway
#2
Xuejun Xu, Zhiping Zhao, Sixiang Guo, Jian Li, Songsong Liu, Yu You, Bing Ni, Huaizhi Wang, Ping Bie
Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28303603/human-il-6-il-17-il-1%C3%AE-and-tnf-%C3%AE-differently-regulate-the-expression-of-pro-inflammatory-related-genes-tissue-factor-and-swine-leukocyte-antigen-class-i-in-porcine-aortic-endothelial-cells
#3
Hanchao Gao, Lu Liu, Yanli Zhao, Hidetaka Hara, Pengfei Chen, Jia Xu, Jia Tang, Ling Wei, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou
BACKGROUND: Pro-inflammatory cytokines play important pathological effects in various diseases and allotransplantation; however, their pathological role in xenotransplantation remains elusive. In pig-to-human cell or organ transplantation, whether porcine cells or organs are activated by human cytokines or not as an important question needs to be investigated. METHODS: We investigated the effect of human IL-6, IFN-γ, IL-17, IL-1β, and TNF-α in xenotransplantation using several in vitro models and porcine aortic endothelial cells (PAECs) as target cells...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28297572/safety-and-efficacy-of-megakaryocytes-induced-from-hematopoietic-stem-cells-in-murine-and-nonhuman-primate-models
#4
Xin Guan, Meng Qin, Yu Zhang, Yanan Wang, Bin Shen, Zhihua Ren, Xinxin Ding, Wei Dai, Yongping Jiang
Because of a lack of platelet supply and a U.S. Food and Drug Administration-approved platelet growth factor, megakaryocytes have emerged as an effective substitute for alleviating thrombocytopenia. Here, we report the development of an efficient two-stage culture system that is free of stroma, animal components, and genetic manipulations for the production of functional megakaryocytes from hematopoietic stem cells. Safety and functional studies were performed in murine and nonhuman primate models. One human cryopreserved cord blood CD34(+) cell could be induced ex vivo to produce up to 1...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#5
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28283480/leveraging-increased-cytoplasmic-nucleoside-kinase-activity-to-target-mtdna-and-oxidative-phosphorylation-in-aml
#6
Sanduni U Liyanage, Rose Hurren, Veronique Voisin, Gaëlle Bridon, Xiaoming Wang, ChangJiang Xu, Neil MacLean, Thirushi P Siriwardena, Marcela Gronda, Dana Yehudai, Shrivani Sriskanthadevan, Daina Avizonis, Aisha Shamas-Din, Mark D Minden, Gary D Bader, Rebecca Laposa, Aaron D Schimmer
Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human AML samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared to normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared to normal hematopoietic samples...
March 10, 2017: Blood
https://www.readbyqxmd.com/read/28270130/mir-124-targets-gata6-to-suppress-cholangiocarcinoma-cell-invasion-and-metastasis
#7
Feng Tian, Jian Chen, Shuguo Zheng, Dajiang Li, Xin Zhao, Peng Jiang, Jianwei Li, Shuguang Wang
BACKGROUND: Our previous study showed that GATA6 plays important roles in cholangiocarcinoma (CCA) cell invasion and metastasis. However, the regulation mechanism of GATA6 in CCA is not clear. In this study, we studied the potential function of miR-124 in CCA and the mechanism of GATA6 regulation. METHODS: The expression levels of miR-124 and GATA6 in cancerous tissues from 57 CCA patients was detected by RT-PCR and IHC. The impact of miR-124 on GATA6 expression in CCA cells was evaluated using cell transfection, xenotransplantation into nude mice and a luciferase reporter assay...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28261878/hemodynamic-and-perioperative-management-in-two-different-preclinical-pig-to-baboon-cardiac-xenotransplantation-models
#8
Tanja Mayr, Andreas Bauer, Bruno Reichart, Sonja Guethoff, Uwe Schoenmann, Matthias Längin, Alessandro Panelli, Alexander Kind, Paolo Brenner, Jan-Michael Abicht
BACKGROUND: The perioperative phase of preclinical cardiac xenotransplantations significantly affects the experimental outcome. Moderate or even severe hemodynamic and respiratory impairment occurs frequently in baboons after receiving a cardiac transplant. The perioperative management of such postoperative instability is very demanding, especially in the experimental setting. We compared perioperative changes of hemodynamic and laboratory findings during orthotopic and heterotopic thoracic cardiac xenotransplantations and describe our monitoring, treatment and intensive care...
March 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28247929/steady-state-peripheral-blood-provides-cells-with-functional-and-metabolic-characteristics-of-real-hematopoietic-stem-cells
#9
A Bourdieu, M Avalon, V Lapostolle, S Ismail, M Mombled, C Debeissat, M Guérinet, P Duchez, J Chevaleyre, M Vlaski-Lafarge, A Villacreces, V Praloran, Z Ivanovic, P Brunet de la Grange
Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood...
March 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28247507/development-of-retrocorneal-membrane-following-pig-to-monkey-penetrating-keratoplasty
#10
Whayoung Lee, Alex Mammen, Deepinder K Dhaliwal, Cassandra Long, Yuko Miyagawa, David Ayares, David K C Cooper, Hidetaka Hara
Recent reports of long-term survival after wild-type (WT) pig-to-monkey corneal xenotransplantation are encouraging. We experienced the rapid development of retrocorneal membranes, a rare complication after corneal allotransplantation (although seen in infants and young children). The original specific aim of the study was to determine the factors associated with successful (young) pig corneal transplantation in monkeys. However, when it was obvious that retrocorneal membranes rapidly developed, our aims became to determine the factors involved in its development after both WT and Genetically engineered (GE ) pig corneal xenotransplantation and to investigate the characteristics of the retrocorneal membrane...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28237390/clinical-xenotransplantation-a-closer-reality-literature-review
#11
Ana María Aristizabal, Luis Armando Caicedo, Juan Manuel Martínez, Manuel Moreno, Gabriel J Echeverri
Xenotransplantation could provide an unlimited supply of organs and solve the current shortage of organs for transplantation. To become a reality in clinical practice, the immunological and physiological barriers and the risk of xenozoonosis that they possess should be resolved. From the immunological point of view, in the last 30 years a significant progress in the production of transgenic pigs has prevented the hyperacute rejection. About xenozoonosis, attention has been focused on the risk of transmission of porcine endogenous retroviruses; however, today, it is considered that the risk is very low and the inevitable transmission should not prevent the clinical xenotransplantation...
February 22, 2017: Cirugía Española
https://www.readbyqxmd.com/read/28225193/human-neural-progenitor-transplantation-rescues-behavior-and-reduces-%C3%AE-synuclein-in-a-transgenic-model-of-dementia-with-lewy-bodies
#12
Natalie R S Goldberg, Samuel E Marsh, Joseph Ochaba, Brandon C Shelley, Hayk Davtyan, Leslie M Thompson, Joan S Steffan, Clive N Svendsen, Mathew Blurton-Jones
Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205459/effects-of-an-antagonistic-analog-of-growth-hormone-releasing-hormone-on-endometriosis-in-a-mouse-model-and-in-vitro
#13
Frank Köster, Li Jin, Yuanming Shen, Andrew V Schally, Ren-Zhi Cai, Norman L Block, Daniela Hornung, Gabriele Marschner, Achim Rody, Jörg B Engel, Dominique Finas
Endometriosis is a benign gynecologic disorder causing dysmenorrhea, pelvic pain, and subfertility. Receptors for the growth hormone-releasing hormone (GHRH) were found in endometriotic tissues. Antagonists of GHRH have been used to inhibit the growth of endometriotic endometrial stromal cells. In this study, the GHRH receptor splice variant (SV) 1 was detected in human endometrial tissue samples by Western blots and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The highest messenger RNA (mRNA) and protein levels of SV1 were found in eutopic endometrium from patients with endometriosis compared to ectopic endometriotic tissues and endometrium from normal patients...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28190795/progress-in-understanding-the-molecular-functions-of-ddx3y-dby-in-male-germ-cell-development-and-maintenance
#14
Alexei A Kotov, Oxana M Olenkina, Baira K Godneeva, Vladimir E Adashev, Ludmila V Olenina
Human DDX3 paralogs are housed on the X chromosome (DDX3X) as well as in the non- recombining region Yq11 of the Y-chromosome (DDX3Y or DBY). A gene encoding RNA helicase DDX3Y is located in the AZoospermia Factor a (AZFa) region of the Y-chromosome and expressed only in male germ cells. Deletions encompassing the DDX3Y gene lead to azoospermia and cause Sertoli Cell-Only Syndrome (SCOS) in humans. SCOS is characterized by a complete germ cell lack with preservation of somatic Sertoli cells. This review summarizes current advances in the study of DDX3Y functions in maintenance and development of early male germ cells...
February 12, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28174392/-heart-transplantation-allograft-and-xenograft
#15
Norihide Fukushima
Prior to starting clinical cardiac allotransplantation, cardiac xenotransplantation was performed in human in 1960s. In 1964, Hardy performed cardiac transplantation using a chimpanzee heart and Bailey performed cardiac transplantation using a baboon heart to an infant with hypoplastic left heart. The use of cyclosporine has greatly improved the outcome of clinical cardiac transplantation and cardiac allotransplantation became an established treatment strategy for the patients with end-stage heart failure. Although concordant cardiac xenotransplantation from a primate to a human may be successfully performed using current immunosuppressive regimen, a primate heart is not a good candidate for cardiac xenograft due to animal light issues and its size...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28164571/establishment-of-a-novel-myelodysplastic-syndrome-mds-xenotransplantation-model
#16
Ling Ma, Xia Zhang, Zhiqiong Wang, Yan Chen, Jia Wei, Lihua Hu
BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disease of the elderly characterized by chronic cytopenia, dysplasia, and a high risk of progression to acute myeloid leukemia (AML). Up until now, few animal models that fully recapitulate clinical features of this disease have been available. METHODS: This study aimed to establish a new MDS xenograft model utilizing a human MDS-derived cell line with heterozygous Y641C mutation of EZH2 (SKM-1). 1 x 107 SKM-1 cells were inoculated into anti-mouse CD122 monoantibody conditioned nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice by intravenous injection...
September 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28160553/small-g-protein-rac-gtpases-regulate-the-maintenance-of-glioblastoma-stem-like-cells-in-vitro-and-in-vivo
#17
Yun-Ju Lai, Jui-Cheng Tsai, Ying-Ting Tseng, Meng-Shih Wu, Wen-Shan Liu, Hoi-Ian Lam, Jei-Hwa Yu, Susan E Nozell, Etty N Benveniste
Glioblastoma is the most common and aggressive malignant brain tumor in adults. The existence of glioblastoma stem cells (GSCs) or stem-like cells (stemloids) may account for its invasiveness and high recurrence. Rac proteins belong to the Rho small GTPase subfamily which regulates cell movement, proliferation, and survival. To investigate whether Rac proteins can serve as therapeutic targets for glioblastoma, especially for GSCs or stemloids, we examined the potential roles of Rac1, Rac2 and Rac3 on the properties of tumorspheres derived from glioblastoma cell lines...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28160329/xenotransplantation-literature-update-november-december-2016
#18
Magie Steinhoff, Raza Naqvi, Christopher Burlak
No abstract text is available yet for this article.
February 4, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28159741/biology-and-relevance-of-human-acute-myeloid-leukemia-stem-cells
#19
Daniel Thomas, Ravindra Majeti
Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly two decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse, and implies that approaches to treatment must eradicate LSCs for cure...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28157735/an-investigation-of-extracellular-histones-in-pig-to-baboon-organ-xenotransplantation
#20
Tao Li, Whayoung Lee, Hidetaka Hara, Cassandra Long, Mohamed Ezzelarab, David Ayares, Hai Huang, Yi Wang, David K C Cooper, Hayato Iwase
BACKGROUND: Serum (extracellular) histone levels are increased in inflammatory states and in the presence of coagulation dysfunction, eg, trauma, chemical/ischemic injury, infection. There is increasing evidence of a systemic inflammatory response associated with the presence of a pig xenograft in a nonhuman primate. We evaluated extracellular histone levels in baboons with various pig xenografts. METHODS: We measured serum histones in baboons with pig heterotopic heart (n=8), life-supporting kidney (n=5), orthotopic liver (n=4), and artery patch (n=9) grafts by ELISA...
February 3, 2017: Transplantation
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