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Xenotransplantation

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https://www.readbyqxmd.com/read/29149987/inhibition-of-porcine-endogenous-retrovirus-by-multi-targeting-micro-rna-against-long-terminal-region
#1
H-C Chung, V-G Nguyen, W-T Oh, T-M-L Huynh, H-J Moon, J-H Lee, H-K Kim, S-J Park, B-K Park
BACKGROUND: There might be much benefit in xenotransplantation, however, the risk of infections across species barriers remains, especially porcine endogenous retrovirus (PERV). To date, many attempts have been made to knock down active PERVs by inhibitory RNA (RNAi) and micro RNA (miRNA), which target different genes of PERV. There are a few studies that have explored whether targeting promoter regions of PERV could exert an inhibition effect. METHODS: miRNAs were automatically selected based on an online program BLOCK-iT RNAi Designer...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149985/acute-rejection-pattern-of-an-outbred-strain-combination-on-mouse-to-rat-heterotopic-heart-xenotransplantation
#2
N Özçay
OBJECTIVES: This study aimed to investigate the acute rejection patterns of outbred mice and rats on a xenotransplantation model. MATERIALS AND METHODS: Thirty male Balb/c mice weighing from 30 to 40 g were used as donors, and 30 male outbred Sprague-Dawley rats weighing from 150 to 200 g were used as recipients for heterotopic heart xenotransplantation models. Animals were allocated into 5 groups according to their killed days, and each group had 6 animals. Animals in group 1 were followed for 1 day and then killed; animals in groups 2, 3, 4, and 5 were followed up 2, 3, 4, and 5 days after transplantation, respectively...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149984/corneal-xenotransplantation-from-pig-to-rhesus-monkey-no-signs-of-transmission-of-endogenous-porcine-retroviruses
#3
A Li, Y Zhang, Y Liu, Z Pan
BACKGROUND: Xenotransplantations of pig corneas have become an attractive alternative to human corneas. Such xenotransplantations carry the danger, however, of transmission of porcine endogenous retroviruses (PERVs). Here, we investigated whether porcine corneas harbor viral DNA and RNA and whether transplantation to a nonhuman primate would lead to host PERV infection. METHODS: Monkey vein endothelial cells (MVECs) were inoculated with porcine aortic endothelial cell (PAEC) supernatants, and DNA and total RNA of MVECs were tested for PERV by polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR) assays...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149983/a-novel-model-of-mouse-to-rat-kidney-xenotransplantation
#4
N Özçay, H Özdemir
Transplantation animal models require 2 animals for each experiment, 1 as a donor and 1 as a recipient. At the present time, developing microsurgical instruments and refining surgical techniques should allow us to reduce the number of animal used for transplantation research. In this study, we aimed to harvest 2 kidneys from 1 donor to be able to minimize the number of animals needed for transplantation studies. For this purpose, we developed a kidney xenotransplantation model from mouse to rat, in which only 1 animal was used as the donor for 2 kidney recipients...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29145696/xenotransplantation-time-to-get-excited
#5
EDITORIAL
Lara C Pullen
No abstract text is available yet for this article.
December 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29143813/ship1-but-not-an-aml-derived-ship1-mutant-suppresses-myeloid-leukemia-growth-in-a-xenotransplantation-mouse-model
#6
M Täger, S Horn, E Latuske, P Ehm, M Schaks, M Nalaskowski, B Fehse, W Fiedler, C Stocking, J Wellbrock, M Jücker
Constitutive activation of the PI3K/AKT signaling pathway is found in ~50-70% of AML patients. The SH2-containing inositol 5-phosphatase 1 (SHIP1) is a negative regulator of PI3K/AKT signaling in hematopoietic cells. SHIP1 knockout mice develop a myeloproliferative syndrome and concomitant deletion of SHIP1 and the tumor suppressor PTEN leads to the development of lethal B-cell lymphomas. In the study presented here, we investigated the role of SHIP1 as a tumor suppressor in myeloid leukemia cells in an in vivo xenograft transplantation model...
November 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29143761/antibody-cross-reactivity-between-porcine-cytomegalovirus-pcmv-and-human-herpesvirus-6-hhv-6
#7
Uwe Fiebig, Angela Holzer, Daniel Ivanusic, Elena Plotzki, Hartmut Hengel, Frank Neipel, Joachim Denner
Porcine cytomegalovirus (PCMV) infection is widely prevalent among pigs, and PCMV is one of the viruses which may be transmitted during xenotransplantation using pig cells, tissues, or organs. While human cytomegalovirus (HCMV) is a major risk factor for allotransplantation, it is still unclear whether PCMV is able to infect human cells or pose a risk for xenotransplantation. Previously, it was shown that transmission of PCMV after pig kidney to non-human primate transplantations resulted in a significantly reduced survival time of the transplanted organ...
October 28, 2017: Viruses
https://www.readbyqxmd.com/read/29135052/enhanced-effect-of-human-mesenchymal-stem-cells-expressing-human-tnf-%C3%AE-r-fc-and-ho-1-gene-on-porcine-islet-xenotransplantation-in-humanized-mice
#8
Han-Sin Lee, Sanghyun Song, Du Yeon Shin, Geun-Soo Kim, Jong-Hyun Lee, Chan Woo Cho, Kyo Won Lee, Hyojun Park, Curie Ahn, Jaeseok Yang, Heung-Mo Yang, Jae Berm Park, Sung-Joo Kim
BACKGROUND: Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood-Mediated Inflammatory Reaction (IBMIR), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor-ɑ receptor type I (sTNF-αR) and heme oxygenase (HO)-1 genes (HO-1/sTNF-αR) have been shown to improve the viability and functionality of porcine islets after transplantation...
November 14, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29133921/metabolomics-identifies-metabolite-biomarkers-associated-with-acute-rejection-after-heart-transplantation-in-rats
#9
Feng Lin, Yi Ou, Chuan-Zhong Huang, Sheng-Zhe Lin, Yun-Bin Ye
The aim of this study was to identify metabolite biomarkers associated with acute rejection after heart transplantation in rats using a LC-MS-based metabolomics approach. A model of heterotopic cardiac xenotransplantation was established in rats, with Wistar rats as donors and SD rats as recipients. Blood and cardiac samples were collected from blank control rats (Group A), rats 5 (Group B) and 7 days (Group C) after heart transplantation, and pretreated rats 5 (Group D) and 7 days (Group E) post-transplantation for pathological and metabolomics analyses...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#10
Xiaoqian Ma, Cejun Yang, Juan Zhang, Jia Wang, Wei Li, Chang Xu, Pengfei Rong, Bin Ye, Minghua Wu, Jianhui Jiang, Shounan Yi, Wei Wang
BACKGROUND: Neonatal pig islet-like cell clusters (NICC) are an attractive source of insulin-producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC after their transplantation due to apoptosis resulted from islet isolation and instant blood-mediated inflammatory reaction remains to be overcome. METHODS: EGM2 medium depleted with hydrocortisone and supplemented with 50 mmol/L isobutylmethylxanthine, 10 mmol/L nicotinamide, and 10 mmol/L glucose was used to culture NICC at day 1, the day after isolation and changed every other day...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29131413/the-effect-of-epitope-based-ligation-of-icam-1-on-survival-and-retransplantation-of-pig-islets-in-nonhuman-primates
#11
Jae-Il Lee, Jiyeon Kim, Yun-Jung Choi, Hi-Jung Park, Hye-Jin Park, Hae Joo Wi, Sunok Yoon, Jun-Seop Shin, Jin Kyun Park, Kyeong Cheon Jung, Eun Bong Lee, Hee Jung Kang, Eung Soo Hwang, Sang-Joon Kim, Chung-Gyu Park, Seong Hoe Park
BACKGROUND: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. MD-3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM-1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD-3 mAb and maintenance with anti-CD154 mAb and sirolimus...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29121878/comparison-of-femtosecond-laser-assisted-corneal-intrastromal-xenotransplantation-and-the-allotransplantation-in-rhesus-monkeys
#12
He Jin, Liangping Liu, Hui Ding, Miao He, Chi Zhang, Xingwu Zhong
BACKGROUND: In our previous study, we showed that both allogeneic and autogeneic small-incision femtosecond laser-assisted corneal intrastromal transplantation are safe and effective surgeries. However, the results of small-incision femtosecond laser-assisted intrastromal xenotransplantation have not yet been explored. Additionally, we suggest that glycerol-dehydrated corneal lamellae might provide a possible alternative for this xenogenic implantation approach. METHODS: Corneal inlay lamellae were produced from rabbits and humans using femtosecond laser-assisted surgeries and were dehydrated in glycerol for 1 week at 4 °C...
November 9, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/29115518/application-of-oligonucleotides-to-construct-a-conditional-targeting-vector-for-porcine-i%C3%AE%C2%BAb%C3%AE
#13
Hegang Li, Xiaona Song, Feng Yang, Hanxun Bao, Xiaolong Lu, Flor M Perez-Campo, Jinshan Zhao
Conditional gene targeting at porcine IκBα may be a solution to delayed xenograft rejection, the main barrier to xenotransplantation. An oligonucleotide‑based method was applied to construct the vector for conditional targeting of porcine IκBα. This method was free from PCR amplification during the assembling of the different vector elements, avoiding introduction of unwanted mutations. With the help of short double‑stranded DNA fragments produced by annealing oligonucleotides, nondirectional cloning has also been avoided...
October 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113556/phospholipase-d-family-member-6-pld6-is-a-surface-marker-for-enrichment-of-undifferentiated-spermatogonia-in-the-pre-pubertal-boars
#14
Pengfei Zhang, Yuwei Qin, Yi Zheng, Wenxian Zeng
Spermatogonial stem cells (SSCs) have a functional ability to maintain self-renewal and sustain production of spermatozoa throughout the reproductive lifespan of a male. Studies on SSCs can thus better understandings of spermatogenesis and unravel the mechanisms for self-renewal and differentiation of male germline stem cells. However, the rarity of SSCs in the testis and the lack of reliable surface markers obstruct the related study and further application of SSCs. This is especially the case in livestock animals...
November 7, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29102562/prostaglandin-e2-increases-lentiviral-vector-transduction-efficiency-of-adult-human-hematopoietic-stem-and-progenitor-cells
#15
Garrett C Heffner, Melissa Bonner, Lauryn Christiansen, Francis J Pierciey, Dakota Campbell, Yegor Smurnyy, Wenliang Zhang, Amanda Hamel, Seema Shaw, Gretchen Lewis, Kendrick A Goss, Olivia Garijo, Bruce E Torbett, Holly Horton, Mitchell H Finer, Philip D Gregory, Gabor Veres
Gene therapy currently in development for hemoglobinopathies utilizes ex vivo lentiviral transduction of CD34(+) hematopoietic stem and progenitor cells (HSPCs). A small-molecule screen identified prostaglandin E2 (PGE2) as a positive mediator of lentiviral transduction of CD34(+) cells. Supplementation with PGE2 increased lentiviral vector (LVV) transduction of CD34(+) cells approximately 2-fold compared to control transduction methods with no effect on cell viability. Transduction efficiency was consistently increased in primary CD34(+) cells from multiple normal human donors and from patients with β-thalassemia or sickle cell disease...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29100399/oxidative-stress-induced-jnk-ap-1-signaling-is-a-major-pathway-involved-in-selective-apoptosis-of-myelodysplastic-syndrome-cells-by-withaferin-a
#16
Karine Z Oben, Sara S Alhakeem, Mary K McKenna, Jason A Brandon, Rajeswaran Mani, Sunil K Noothi, Liu Jinpeng, Shailaja Akunuru, Sanjit K Dhar, Inder P Singh, Ying Liang, Chi Wang, Ahmed Abdel-Latif, Harold F Stills, Daret K St Clair, Hartmut Geiger, Natarajan Muthusamy, Kaoru Tohyama, Ramesh C Gupta, Subbarao Bondada
Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug therapies but a majority of responders relapse within 2-3 years. There is therefore a compelling need to identify potential new therapies for MDS treatment. We utilized the MDS-L cell line to investigate the anticancer potential and mechanisms of action of a plant-derived compound, Withaferin A (WFA), in MDS...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099728/heart-xenotransplantation
#17
Joshua L Chan, Muhammad M Mohiuddin
PURPOSE OF REVIEW: Cardiac xenotransplantation has entered an exciting era, marked by numerous considerable advances in the field, and continues to be of great interest because of its potential ability in ameliorating the current constraints of limited allograft availability. This review aims to examine recent progress in this rapidly changing discipline. RECENT FINDINGS: Although several hurdles remain, the use of rapidly evolving transgenic technology, in combination with novel immunosuppression regimens, has the potential to address current allogenic donor pool constraints and mechanical circulatory system device limitations...
December 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29089643/targeting-acute-myeloid-leukemia-by-drug-induced-c-myb-degradation
#18
V Walf-Vorderwülbecke, K Pearce, T Brooks, M Hubank, M M van den Heuvel-Eibrink, C M Zwaan, S Adams, D Edwards, J Bartram, S Samarasinghe, P Ancliff, A Khwaja, N Goulden, G Williams, J de Boer, O Williams
Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. The transcription factor c-MYB has been shown to play a central role in the development and progression of AML driven by several different oncogenes, including mixed lineage leukemia (MLL)-fusion genes...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29089623/enzalutamide-inhibits-testosterone-induced-growth-of-human-prostate-cancer-xenografts-in-zebrafish-and-can-induce-bradycardia
#19
Nicole Melong, Shelby Steele, Morgan MacDonald, Alice Holly, Colin C Collins, Amina Zoubeidi, Jason N Berman, Graham Dellaire
The zebrafish has become a popular human tumour xenograft model, particularly for solid tumours including prostate cancer (PCa). To date PCa xenotransplantation studies in zebrafish have not been performed in the presence of testosterone, even when employing androgen-dependent cell models, such as the LNCaP cell line. Thus, with the goal of more faithfully modelling the hormonal milieu in which PCa develops in humans, we sought to determine the effects of exogenous testosterone on the growth of LNCaP, or androgen-independent C4-2 cells xenografted into zebrafish embryos...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#20
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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