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Xenotransplantation

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https://www.readbyqxmd.com/read/28798043/inactivation-of-porcine-endogenous-retrovirus-in-pigs-using-crispr-cas9
#1
Dong Niu, Hong-Jiang Wei, Lin Lin, Haydy George, Tao Wang, I-Hsiu Lee, Hong-Ye Zhao, Yong Wang, Yinan Kan, Ellen Shrock, Emal Lesha, Gang Wang, Yonglun Luo, Yubo Qing, Deling Jiao, Heng Zhao, Xiaoyang Zhou, Shouqi Wang, Hong Wei, Marc Güell, George M Church, Luhan Yang
Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concern on pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. Earlier, we demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. Here, we confirmed that PERVs infect human cells, and observed the horizontal transfer of PERVs among human cells...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28771838/human-regulatory-macrophages-are-potent-in-suppression-of-the-xenoimmune-response-via-indoleamine-2-3-dioxygenase-involved-mechanism-s
#2
Fei Guo, Min Hu, Dandan Huang, Yuanfei Zhao, Benjamin Heng, Gilles Guillemin, Chai K Lim, Wayne J Hawthorne, Shounan Yi
BACKGROUND: For xenotransplantation to truly succeed, we must develop immunomodulatory strategies to suppress the xenoimmune response but by minimizing immunosuppression over the long term. Regulatory macrophages (Mreg) have been shown to suppress polyclonal T-cell proliferation in vitro and prolong allograft survival in vivo. However, the question of whether they are capable of suppressing xenoimmune responses remains unknown. This study assessed the potential of human Mreg to be used as an effective immunomodulatory method in xenotransplantation...
August 2, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28767742/basic-fibroblast-growth-factor-improved-angiogenesis-of-vitrified-human-ovarian-tissues-after-in-vitro-culture-and-xenotransplantation
#3
B J Kang, Y Wang, L Zhang, S W Li
BACKGROUND: Basic fibroblast growth factor is a potent angiogenic factor. OBJECTIVE: To study the concentration and in vitro culture time of bFGF that maximize the angiogenesis for transplanted human ovarian tissues. MATERIALS AND METHODS: Vitrified and rewarmed human ovarian tissues were cultured in vitro with bFGF (0, 25, 50, 100, 150 and 200 ng/ml) for different periods (1 h, 2 d, 5 d and 7 d) before transplantation. The effect of bFGF on follicle survival was studied by evaluating the pregraft group, control group (no bFGF) and bFGF-treated group...
May 2017: Cryo Letters
https://www.readbyqxmd.com/read/28766011/rnai-screen-identifies-essential-regulators-of-human-brain-metastasis-initiating-cells
#4
Mohini Singh, Chitra Venugopal, Tomas Tokar, Kevin R Brown, Nicole McFarlane, David Bakhshinyan, Thusyanth Vijayakumar, Branavan Manoranjan, Sujeivan Mahendram, Parvez Vora, Maleeha Qazi, Manvir Dhillon, Amy Tong, Kathrin Durrer, Naresh Murty, Robin Hallet, John A Hassell, David R Kaplan, Jean-Claude Cutz, Igor Jurisica, Jason Moffat, Sheila K Singh
Brain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs)...
August 1, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28764863/cellular-expression-in-vitro-and-in-vivo-confirmation-of-gaec1-oncogenic-properties-in-colon-cancer
#5
Riajul Wahab, Vinod Gopalan, Farhadul Islam, Robert A Smith, Bin Qiao, Alfred K Lam
GAEC1 (Gene amplified in esophageal cancer 1) alterations have oncogenic properties in oesophageal squamous cell carcinomas and frequent amplifications of the gene were noted in colorectal adenocarcinomas. However, the subcellular localization and expression of GAEC1 at the protein level have never been reported in human cancer cells. The present study aimed to investigate whether GAEC1 is differentially expressed in different stages of colon cancer and to elucidate its underlying cellular and molecular mechanism in colon cancer progression...
July 26, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28759462/pig-islet-xenotransplantation
#6
Maheswaran Dhanasekaran, Johnathan J George, Gopalakrishnan Loganathan, Siddharth Narayanan, Michael G Hughes, Stuart K Williams, Appakalai N Balamurugan
PURPOSE OF REVIEW: The current article reviews the rationale, sources and preparation of pig islets for xenotransplantation, and presents current progress in solving the problems associated with establishing pig islet transplant as a clinical treatment for type 1 diabetes. SUMMARY: Islet transplantation is an effective treatment option for type 1 diabetes, but the available supply of human pancreases is insufficient to meet the need and demand for obtaining islets...
July 28, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28756496/cryopreservation-of-human-ovarian-tissue-using-the-silver-closed-vitrification-system
#7
Zhun Xiao, Yaoyao Zhang, Wei Fan
PURPOSE: The aim of this study is to evaluate the feasibility of using a hand-made silver container for the cryopreservation of human ovarian cortex. METHODS: Human ovarian cortex tissues were vitrified using an open vitrification system (OVS) of needle immersed vitrification (NIV) and two closed vitrification systems (CVS) of a plastic vial (plastic CVS) and a silver container (silver CVS). Outcomes of vitrification were evaluated morphologically and histologically by in vitro culture and xenotransplantation...
July 29, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28741700/financial-aspects-of-organ-procurement-from-deceased-donors-in-the-usa-relevance-to-xenotransplantation
#8
REVIEW
Ryan J Saari, David K C Cooper
When clinical xenotransplantation is introduced, the costs associated with acquisition of a genetically engineered pig organ are as yet unknown. How will these costs compare with those currently associated with the acquisition of deceased human organs? An understanding of the financial aspects of deceased organ and tissue procurement in the USA is therefore worthwhile. We have therefore attempted to review certain economic aspects of non-profit and for-profit organizations that provide cadaveric organs and/or tissues for purposes of transplantation into patients with end-stage organ failure, cellular deficiencies, or in need of reconstructive procedures...
July 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28741697/xenotransplantation-literature-update-may-june-2017
#9
Eric M Walters, Karl Kerns, Christopher Burlak
No abstract text is available yet for this article.
July 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28740957/xenotransplantation-of-human-cryopreserved-parathyroid-tissue-isolated-from-parathyroid-adenomas-to-normocalcemic-rabbits
#10
Erhan Ayşan, Yiğit Düzköylü, İsmail Can, Nur Büyükpınarbaşılı
OBJECTIVE: Parathyroid allotransplantation is a new method for the treatment of permanent hypoparathyrodism. Adenoma cells are not used for transplantation because of the potential for functional or histopathologic transformation. In this study, we transplanted human adenomatous parathyroid cells to rabbits. MATERIAL AND METHODS: Parathyroid adenoma tissue taken from a male patient was cryopreserved and transplanted into seven New Zealand white rabbits (mean weight, 3700±220 g; mean age, 4...
2017: Turk J Surg
https://www.readbyqxmd.com/read/28737658/regulation-of-clinical-xenotransplantation-time-for-a-reappraisal
#11
David K C Cooper, Richard N Pierson, Bernhard J Hering, Muhammad M Mohiuddin, Jay A Fishman, Joachim Denner, Curie Ahn, Agnes M Azimzadeh, Leo H Buhler, Peter J Cowan, Wayne J Hawthorne, Takaaki Kobayashi, David H Sachs
The continual critical shortage of organs and cells from deceased human donors has stimulated research in the field of cross-species transplantation (xenotransplantation), with the pig selected as the most suitable potential source of organs. Since the US Food and Drug Administration concluded a comprehensive review of xenotransplantation in 2003, considerable progress has been made in the experimental laboratory to improve cell and organ xenograft survival in several pig-to-nonhuman primate systems that offer the best available models to predict clinical outcomes...
August 2017: Transplantation
https://www.readbyqxmd.com/read/28736027/suppression-of-delayed-xenograft-rejection-by-resveratrol-in-a-hamster-to-rat-cardiac-transplantation-model
#12
Y Lian, C Gao, Y Wu, J Xia, Y Leng, Y Liu, M Zhu, J Chen, Z Qi
BACKGROUND: Delayed xenograft rejection (DXR) is an insurmountable barrier for xenotransplantation. Previous studies reported that hamster hearts transplanted into rats undergo DXR and stop functioning after the cessation of immunosuppression. Herein, we investigated the effects of resveratrol on preventing DXR in a hamster-to-rat vascularized cardiac xenograft model. METHODS: Hamster hearts were engrafted into Lewis rat recipients. Recipient rats received a graft acceptance-inducing treatment of leflunomide and FK506 for 2 weeks to prevent acute xenograft rejection (AXR)...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28730558/transplantation-sites-for-porcine-islets
#13
Rebecca A Stokes, Denbigh M Simond, Heather Burns, Anita T Patel, Philip J O'Connell, Jenny E Gunton, Wayne J Hawthorne
AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28725880/role-of-intrinsic-factors-in-the-growth-of-transplanted-organs-following-transplantation
#14
Jigesh A Shah, Tatsu Tanabe, Kazuhiko Yamada
Shortages in the availability of transplantable organs have forced the transplant community to seek alternative methods to increase the supply of available organs. In our recent study following α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidney xenotransplantation, we found that certain recipients developed increased serum creatinine, possibly due to the rapid growth of orthotopic pig grafts in smaller baboon recipients. To test our hypothesis, we assessed whether the growth of outbred (Yorkshire) organ transplants (kidney and lung) in miniature swine was regulated by intrinsic (graft) factors...
June 2017: Journal of Immunobiology
https://www.readbyqxmd.com/read/28720126/a-small-molecule-cytokine-combination-enhances-hematopoietic-stem-cell-proliferation-via-inhibition-of-cell-differentiation
#15
Lan Wang, Xin Guan, Huihui Wang, Bin Shen, Yu Zhang, Zhihua Ren, Yupo Ma, Xinxin Ding, Yongping Jiang
BACKGROUND: Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. METHODS: Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34(+) cell expansion ex vivo...
July 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28718514/aldehyde-dehydrogenase-1-a1-regulates-energy-metabolism-in-adipocytes-from-different-species
#16
Kefeng Yang, Christopher Adin, Qiwen Shen, Ly James Lee, Lianbo Yu, Paolo Fadda, Arpad Samogyi, Kathleen Ham, Lu Xu, Chen Gilor, Ouliana Ziouzenkova
BACKGROUND: Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for interspecies cross talk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes...
July 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28715486/anti-neu5gc-and-anti-non-neu5gc-antibodies-in-healthy-humans
#17
Bingsi Gao, Cassandra Long, Whayoung Lee, Zhongqiang Zhang, Xiaotian Gao, Doug Landsittel, Mohamed Ezzelarab, David Ayares, Yuliang Huang, David K C Cooper, Yi Wang, Hidetaka Hara
Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28714241/cytokine-profiles-in-tibetan-macaques-following-%C3%AE-1-3-galactosyltransferase-knockout-pig-liver-xenotransplantation
#18
Zhuochao Zhang, Xiao Li, Hong Zhang, Xuan Zhang, Hui Chen, Dengke Pan, Hongchen Ji, Liang Zhou, Juan Ling, Jingshi Zhou, Shuqiang Yue, Desheng Wang, Zhaoxu Yang, Kaishan Tao, Kefeng Dou
BACKGROUND: Pig-to-nonhuman primate orthotopic liver xenotransplantation is often accompanied by thrombocytopenia and coagulation disorders. Furthermore, the release of cytokines can trigger cascade reactions of coagulation and immune attacks within transplant recipients. To better elucidate the process of inflammation in liver xenograft recipients, we utilized a modified heterotopic auxiliary liver xenotransplantation model for xeno-immunological research. We studied the cytokine profiles and the relationship between cytokine levels and xenograft function after liver xenotransplantation...
July 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28711492/species-specific-real-time-rt-pcr-analysis-of-expression-of-stromal-cell-genes-in-a-tumor-xenotransplantation-model-in-mice
#19
Evzen Krepela, Petr Busek, Marek Hilser, Zdislava Vanickova, Aleksi Sedo
Human tumor xenografts in mice together with the species-specific analysis of expressed genes allow to study the molecular processes driving tumor growth and progression in vivo and help to develop and evaluate anticancer therapies. In the present work, we designed and validated species-specific real-time RT-PCR assays for discrimination and quantitation of expression of human and mouse transcripts in cancer and stromal cells including dipeptidyl peptidase (DPP) 4, DPP8, DPP9, fibroblast activation protein (FAP) and CXC chemokine receptor 4 in mixed human-mouse biological samples...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28702183/induction-of-autoimmune-abdominal-aortic-aneurysm-in-pigs-a-novel-large-animal-model
#20
Sara Schødt Riber, Mulham Ali, Sara Hveding Bergseth, Jane Stubbe, Michael Stenger, Carsten Behr-Rasmussen, Jes Sanddal Lindholt
BACKGROUND: Abdominal aortic aneurysm (AAA) is a common disease with a high mortality. Many animal models have been developed to further understand the pathogenesis of the disease, but no large animal model has been developed to investigate the autoimmune aspect of AAA formation. The aim of this study was to develop a large animal model for abdominal aortic aneurysm induction through autoimmunity by performing sheep-to-pig xenotransplantation. METHODS: Six pigs underwent a xenotransplantation procedure where the infrarenal porcine aorta was replaced by a decellularized sheep aorta...
August 2017: Annals of Medicine and Surgery
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