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Sarita Panula, Ahmed Reda, Jan-Bernd Stukenborg, Cyril Ramathal, Meena Sukhwani, Halima Albalushi, Daniel Edsgärd, Michiko Nakamura, Olle Söder, Kyle E Orwig, Shinya Yamanaka, Renee A Reijo Pera, Outi Hovatta
The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation...
2016: PloS One
J Wu, A Platero Luengo, M A Gil, K Suzuki, C Cuello, M Morales Valencia, I Parrilla, C A Martinez, A Nohalez, J Roca, E A Martinez, J C Izpisua Belmonte
More than eighteen years have passed since the first derivation of human embryonic stem cells (ESCs), but their clinical use is still met with several challenges, such as ethical concerns regarding the need of human embryos, tissue rejection after transplantation and tumour formation. The generation of human induced pluripotent stem cells (iPSCs) enables the access to patient-derived pluripotent stem cells (PSCs) and opens the door for personalized medicine as tissues/organs can potentially be generated from the same genetic background as the patient recipients, thus avoiding immune rejections or complication of immunosuppression strategies...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
M Mikla, A Rios, A Lopez-Navas, D Kilanska, B Gorzkowicz, L Martinez-Alarcón, G Ramis, P Ramirez, M J Lopez Montesinos
BACKGROUND: The shortage of organs has made it necessary to look for new alternatives as xenotransplantation. The objective of this study was to analyze the attitudes of Polish nursing students toward organ donation of nonhuman origin, and to determine the factors that affect them. METHODS: Year 2011-2012. Nursing students of the University of Poland. Sampling points in 5 compulsory-attendance nursing courses with a completion rate of fulfillment of 80%. Validated questionnaire (PCID-XenoTx Rios) filled out anonymously and self-administered...
September 2016: Transplantation Proceedings
Masayuki Shimoda, Shinichi Matsumoto
Allogeneic islet transplantation has become a viable treatment for patients with unstable type 1 diabetes; however, donor shortage and the necessity for immunosuppressive drugs are the major drawbacks of this approach. Microencapsulated porcine islet xenotransplantation could solve these drawbacks. Clinical porcine islet xenotransplantation as well as microencapsulated islet transplantation has been conducted without significant side effects. However, these transplantations are not as efficacious as allogeneic naked islet transplantation...
2017: Methods in Molecular Biology
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Hanchao Gao, Chengjiang Zhao, Xi Xiang, Yong Li, Yanli Zhao, Zesong Li, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Zhiming Cai, Lisha Mou
Gene-knockout pigs hold great promise as a solution to the shortage of organs from donor animals for xenotransplantation. Several groups have generated gene-knockout pigs via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) and somatic cell nuclear transfer (SCNT). Herein, we adopted a simple and micromanipulator-free method, handmade cloning (HMC) instead of SCNT, to generate double gene-knockout pigs. First, we applied the CRISPR/Cas9 system to target α1,3-galactosyltransferase (GGTA1) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes simultaneously in porcine fetal fibroblast cells (PFFs), which were derived from wild-type Chinese domestic miniature Wuzhishan pigs...
October 8, 2016: Journal of Reproduction and Development
L Cavicchioli, S Ferraresso, S Westmoreland, S Kaliyaperumal, H Knight, C Crossan, L Scobie, A Danesi, M Vadori, D Trez, R Aron Badin, P Hantraye, E Cozzi
Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations that occur in the setting of depressed T-cell function due to immunosuppressive therapy used following solid organ transplantation, hematopoietic stem cell transplantation, and also xenotransplantation. In the present study, 28 immunosuppressed parkinsonian Macaca fascicularis were intracerebrally injected with wild-type or CTLA4-Ig transgenic porcine xenografts to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation...
September 30, 2016: Veterinary Pathology
Burcin Ekser, Rita Bottino, David K C Cooper
No abstract text is available yet for this article.
September 24, 2016: EBioMedicine
Jan-Michael Abicht, Ioannis Kourtzelis, Bruno Reichart, Sophia Koutsogiannaki, Alexandra Primikyri, John D Lambris, Triantafyllos Chavakis, Lesca Holdt, Alexander Kind, Sonja Guethoff, Tanja Mayr
BACKGROUND: The complement system plays a crucial role in acute xenogeneic reactions after cardiac transplantation. We used an ex vivo perfusion model to investigate the effect of Cp40, a compstatin analog and potent inhibitor of complement at the level of C3. METHODS: Fifteen wild-type pig hearts were explanted, cardiopleged, and reperfused ex vivo after 150 minutes of cold ischemia. Hearts were challenged in a biventricular working heart mode to evaluate cardiac perfusion and function...
September 27, 2016: Xenotransplantation
Vladimir A Morozov, Shaun Wynyard, Shinichi Matsumoto, Adrian Abalovich, Joachim Denner, Robert Elliott
Xenotransplantation of pig islet cells is a promising alternative for the treatment of diabetes with insulin and may help to prevent numerous late complications such as blindness and amputation. First encouraging results using porcine islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated islet cells from the well-characterised Auckland Island pigs were used...
September 24, 2016: Virus Research
M-O Timsit, J Branchereau, R Thuret, F Kleinclauss
OBJECTIVES: To report major findings that may build the future of kidney transplantation. MATERIAL AND METHODS: Relevant publications were identified through Medline ( and Embase ( database from 1960 to 2016 using the following keywords, in association, "bio-engineering; heterotransplantation; immunomodulation; kidney; regenerative medicine; xenotransplantation". Articles were selected according to methods, language of publication and relevance...
September 21, 2016: Progrès en Urologie
Christopher Burlak
No abstract text is available yet for this article.
September 2016: Xenotransplantation
R K F Fung, I H Kerridge
In Australia, and internationally, the shortage of organ and tissue donors significantly limits the number of patients with critical organ or tissue failure who are able to receive a transplant each year. The rationale for xenotransplantation - the transplantation of living cells, tissues or organs from one species to another - is to meet this shortfall in human donor material. While early clinical trials showed promise, particularly in patients with type I diabetes whose insulin dependence could be temporarily reversed by the transplantation of porcine islet cells, these benefits have been balanced with scientific, clinical and ethical concerns revolving around the risks of immune rejection and the potential transmission of porcine endogenous retroviruses or other infectious agents from porcine grafts to human recipients...
September 2016: Internal Medicine Journal
Vladimir A Morozov, Elena Plotzki, Avi Rotem, Uriel Barkai, Joachim Denner
BACKGROUND: To prevent transmission of zoonotic microorganisms from pig transplants to human recipients when performing xenotransplantation using pig cells, tissues, or organs, donor pigs have to be carefully characterized. Göttingen minipigs (GöMP) are often used for various biomedical investigations and are well characterized concerning the presence of numerous bacteria, fungi, viruses, and parasites. Recently, we studied the prevalence and expression of porcine endogenous retroviruses and the prevalence of hepatitis E virus (HEV) in GöMP...
September 11, 2016: Xenotransplantation
Hyun Ju Yoo, Ji-Eun Kim, Ja Yoon Gu, Sae Bom Lee, Hyun Joo Lee, Ho Young Hwang, Yoohwa Hwang, Young Tae Kim, Hyun Kyung Kim
BACKGROUND: Neutrophils play a role in xenograft rejection. When neutrophils are stimulated, they eject the DNA-histone complex into the extracellular space, called neutrophil extracellular traps (NET). We investigated whether NET formation actively occurs in the xenograft and contributes to coagulation and endothelial activation. METHODS: Human whole blood was incubated with porcine aortic endothelial cells (pEC) from wild-type or α1,3-galactosyltransferase gene-knockout (GTKO) pigs...
September 10, 2016: Xenotransplantation
Bjoern Petersen, Antje Frenzel, Andrea Lucas-Hahn, Doris Herrmann, Petra Hassel, Sabine Klein, Maren Ziegler, Klaus-Gerd Hadeler, Heiner Niemann
BACKGROUND: Xenotransplantation is considered to be a promising solution to the growing demand for suitable donor organs for transplantation. Despite tremendous progress in the generation of pigs with multiple genetic modifications thought to be necessary to overcoming the severe rejection responses after pig-to-non-human primate xenotransplantation, the production of knockout pigs by somatic cell nuclear transfer (SCNT) is still an inefficient process. Producing genetically modified pigs by intracytoplasmic microinjection of porcine zygotes is an alluring alternative...
September 2016: Xenotransplantation
Jeffrey M Gaudet, Amanda M Hamilton, Yuanxin Chen, Matthew S Fox, Paula J Foster
PURPOSE: Cellular MRI) was used to detect implanted human mesenchymal stem cells (hMSCs) and the resulting macrophage infiltration that occurs in response to xenotransplantation. METHODS: Human mesenchymal stem cells were prelabeled with a fluorine-19 ((19) F) agent prior to implantation, allowing for their visualization and quantification over time. Following implantation of 1 × 10(6) (19) F-labeled hMSCs into the mouse hind limb, longitudinal imaging was performed to monitor the stem cell graft...
September 9, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Chiara Tommasino, Lucrezia Gambardella, Maria Buoncervello, Roger J Griffin, Bernard T Golding, Manuela Alberton, Daniele Macchia, Massimo Spada, Bruna Cerbelli, Giulia d'Amati, Walter Malorni, Lucia Gabriele, Anna Maria Giammarioli
BACKGROUND: The antimalarial drug Pyrimethamine has been suggested to exert an antitumor activity by inducing apoptotic cell death in cancer cells, including metastatic melanoma cells. However, the dose of Pyrimethamine to be considered as an anticancer agent appears to be significantly higher than the maximum dose used as an antiprotozoal drug. METHODS: Hence, a series of Pyrimethamine analogs has been synthesized and screened for their apoptosis induction in two cultured metastatic melanoma cell lines...
2016: Journal of Experimental & Clinical Cancer Research: CR
Shinichi Matsumoto, Adrian Abalovich, Carlos Wechsler, Shaun Wynyard, Robert B Elliott
BACKGROUND: Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes. However, the donor shortage and the necessity of the immunosuppressive drugs are two major issues. To solve these issues, we performed islet xenotransplantation using encapsulated neonatal porcine islets without immunosuppressive drugs. METHODS: Two different doses (approximately 5000IEQ/kg and 10,000IEQ/kg) of encapsulated neonatal porcine islets were transplanted twice (total approximately 10,000IEQ/kg and 20,000IEQ/kg) into four type 1 diabetic patients in each group (total 8 patients)...
August 24, 2016: EBioMedicine
Masahiro Sato, Kosuke Maeda, Miyu Koriyama, Emi Inada, Issei Saitoh, Hiromi Miura, Masato Ohtsuka, Shingo Nakamura, Takayuki Sakurai, Satoshi Watanabe, Kazuchika Miyoshi
The introduction of multigene constructs into single cells is important for improving the performance of domestic animals, as well as understanding basic biological processes. In particular, multigene constructs allow the engineering and integration of multiple genes related to xenotransplantation into the porcine genome. The piggyBac (PB) transposon system allows multiple genes to be stably integrated into target genomes through a single transfection event. However, to our knowledge, no attempt to introduce multiple genes into a porcine genome has been made using this system...
2016: International Journal of Molecular Sciences
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