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Xenotransplantation

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https://www.readbyqxmd.com/read/28526679/succession-of-transiently-active-tumor-initiating-cell-clones-in-human-pancreatic-cancer-xenografts
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28489305/prolonged-survival-following-pig-to-primate-liver-xenotransplantation-utilizing-exogenous-coagulation-factors-and-co-stimulation-blockade
#5
J A Shah, M S Patel, N Elias, N Navarro-Alvarez, I Rosales, R A Wilkinson, N J Louras, M Hertl, J A Fishman, R B Colvin, A B Cosimi, J F Markmann, D H Sachs, P A Vagefi
Since the first attempt in 1968, survival following pig-to-primate liver xenotransplantation (LXT) has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous post-transplant infusion of human prothrombin concentrate complex and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone and co-stimulation blockade (belatacept, n=3 or anti-CD40mAb, n=1) to extend survival. Baboon #1 remained well until POD25 when euthanasia was required due to cholestasis and plantar ulcers...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28484448/anti-cd47-antibody-as-a-targeted-therapeutic-agent-for-human-lung-cancer-and-cancer-stem-cells
#6
Liang Liu, Lin Zhang, Lin Yang, Hui Li, Runmei Li, Jinpu Yu, Lili Yang, Feng Wei, Cihui Yan, Qian Sun, Hua Zhao, Fan Yang, Hao Jin, Jian Wang, Shizhen Emily Wang, Xiubao Ren
Accumulating evidence indicates that a small subset of cancer cells, termed the tumor-initiating cells or cancer stem cells (CSCs), construct a reservoir of self-sustaining cancer cells with the characteristic ability to self-renew and maintain the tumor mass. The CSCs play an important role in the tumor initiation, development, relapse, metastasis, and the ineffectiveness of conventional cancer therapies. CD47 is a ligand for signal-regulatory protein-α expressed on phagocytic cells and functions to inhibit phagocytosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28474535/long-term-propagation-of-porcine-undifferentiated-spermatogonia
#7
Pengfei Zhang, Xiaoxu Chen, Yi Zheng, Jinsheng Zhu, Yuwei Qin, Yinghua Lv, Wenxian Zeng
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis and fertility throughout the adult life of a male. Genetic manipulations of SSCs combined with germ cell transplantation present a novel approach for gene therapy and production of genetically modified animals. However, the rarity of SSCs within mammalian testes remains an impediment to related applications that require sufficient numbers of SSCs, making in vitro expansion of SSCs a prerequisite. Nevertheless, long-term culture systems of SSCs from large animals have not been established yet...
May 5, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28474373/angiopoietin-1-and-angiopoietin-2-protect-porcine-iliac-endothelial-cells-from-human-antibody-mediated-complement-dependent-cytotoxicity-through-phosphatidylinositide-3-kinase-akt-pathway-activation
#8
Hanchao Gao, Pengfei Chen, Ling Wei, Jia Xu, Lu Liu, Yanli Zhao, Hidetaka Hara, Dengke Pan, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou
Cytokines play crucial roles in inflammation, but their role in xenotransplantation remains elusive. We assessed the role of several cytokines using an in vitro model of human antibody-mediated complement-dependent cytotoxicity (CDC). Recombinant human angiopoietin-1 (Ang-1) protected porcine iliac endothelial cells (PIECs) from human antibody-mediated CDC. Interestingly, human angiopoietin-2 (Ang-2) had a similar protective effect on PIECs. By flow cytometry analysis, the extent of human IgM and IgG binding to PIECs did not decrease when PIECs were exposed to Ang-1/Ang-2...
May 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28468778/modeling-of-patient-derived-xenografts-in-colorectal-cancer
#9
Anastasia Katsiampoura, Kanwal Raghav, Zhi-Qin Jiang, David G Menter, Andreas Varkaris, Maria P Morelli, Shanequa Manuel, Ji Wu, Alexey V Sorokin, Bahar Salimian Rizi, Cristopher Bristow, Feng Tian, Susan Airhart, Mingshan Cheng, Bradley M Broom, Jeffrey Morris, Michael J Overman, Garth Powis, Scott Kopetz
Developing realistic preclinical models using clinical samples that mirror complex tumor biology and behavior are vital to advancing cancer research. While cell-line cultures have been helpful in generating preclinical data, the genetic divergence between these and corresponding primary tumors has limited clinical translation. Conversely, patient derived xenografts (PDXs) in colorectal cancer (CRC) are highly representative of the genetic and phenotypic heterogeneity in the original tumor. Coupled with high-throughput analyses and bioinformatics, these PDXs represent robust preclinical tools for biomarkers, therapeutic target and drug discovery...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28468777/the-multi-kinase-inhibitor-debio-0617b-reduces-maintenance-and-self-renewal-of-primary-human-aml-cd34-stem-progenitor-cells
#10
Maximilien Murone, Ramin Radpour, Antoine Attinger, Anne Vaslin Chessex, Anne-Laure Huguenin, Christian M Schürch, Yara Banz, Saumitra Sengupta, Michel Aguet, Stefania Rigotti, Yogeshwar Bachhav, Frederic Massiere, Murali Ramachandra, Andres McAllister, Carsten Riether
Acute myelogenous leukemia (AML) is initiated and maintained by leukemia stem cells (LSCs). LSCs are therapy-resistant, cause relapse and represent a major obstacle for the cure of AML. Resistance to therapy is often mediated by aberrant tyrosine kinase (TK) activation. These TKs primarily activate downstream signaling via STAT3/STAT5. In this study, we analyzed the potential to therapeutically target aberrant TK signaling and to eliminate LSCs via the multi-TK inhibitor Debio 0617B. Debio 0617B has a unique profile targeting key kinases upstream of STAT3/STAT5 signaling such as JAK, SRC, ABL and class III/V receptor TKs...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28462511/altered-expression-of-enos-prostacyclin-synthase-prostaglandin-g-h-synthase-and-thromboxane-synthase-in-porcine-aortic-endothelial-cells-after-exposure-to-human-serum-relevance-to-xenotransplantation
#11
Pengfei Chen, Hanchao Gao, Ying Lu, Huirong Nie, Zhaoming Liu, Yu Zhao, Nana Fan, Qingjian Zou, Yifan Dai, Aifa Tang, Hidetaka Hara, Zhiming Cai, David K C Cooper, Liangxue Lai, Lisha Mou
Under normal conditions, the activity of platelets is stringently and precisely balanced between activation and quiescent state. This guarantees rapid hemostasis and avoids uncontrolled thrombosis. However, excessive platelet activation and resulting thrombotic microangiopathy are frequently observed in pig-to-primate xenotransplantation models. Endothelium-derived inhibitory mechanisms play an important role in regulation of platelet activation. These mainly include nitric oxide (NO), prostacyclin PGI2 and adenosine, which are synthesized by endothelial nitric oxide synthases (eNOS), prostacyclin synthase, and CD39/CD73, respectively...
April 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28457422/co-transplantation-of-xenogeneic-bone-marrow-derived-mesenchymal-stem-cells-alleviates-rejection-of-pancreatic-islets-in-non-obese-diabetic-mice
#12
C Corradi-Perini, T M Santos, N O S Camara, M C Riella, C A M Aita
Bone marrow-mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28456796/alpha1-act-functions-as-a-tumour-suppressor-in-hepatocellular-carcinoma-by-inhibiting-the-pi3k-akt-mtor-signalling-pathway-via-activation-of-pten
#13
Hanzhang Zhu, Qiaoyu Liu, Junwei Tang, Yu Xie, Xiaoliang Xu, Ruyi Huang, Yuanguangyan Zhang, Kangpeng Jin, Beicheng Sun
BACKGROUND & AIMS: To investigate the expression and prognostic value of α1-ACT (Alpha1-antichymotrypsin) in patients with HCC (hepatocellular carcinoma) and identify the mechanism by which α1-ACT inhibits proliferation and promotes apoptosis of HCC. METHODS: We first measured α1-ACT expression levels and determined their relationship with the clinicopathological characteristics and prognosis of patients with HCC.We then established stable HCC cell lines with both α1-ACT overexpression and knockdown and performed a functional analysis in vitro...
April 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28448818/pegylated-bilirubin-nanoparticle-as-an-anti-oxidative-and-anti-inflammatory-demulcent-in-pancreatic-islet-xenotransplantation
#14
Min Jun Kim, Yonghyun Lee, Sangyong Jon, Dong Yun Lee
Transplanted islets suffer hypoxic stress, which leads to nonspecific inflammation. This is the major cause of islet graft failure during the early stage of intrahepatic islet transplantation. Although bilirubin has shown potent anti-oxidative and anti-inflammatory functions, its clinical applications have been limited due to its insolubility and short half-life. To overcome this problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28447930/a-novel-and-simple-method-for-tracheal-intubation-in-a-swine-model-preparing-for-the-era-of-xenotransplantation
#15
Hyub Huh, Hyong Hwan Lim, Ji Yeong Kim, Hye Won Shin, Hae Ja Lim, Suk Min Yoon, Seung Zhoo Yoon, Hye Won Lee
OBJECTIVES: Organ transplant in humans is an established therapy for a variety of end-stage organ diseases. However, due to organ shortages and lack of donors, the need for xenotransplant has gradually increased. Xenotransplantation has great potential to solve many of the problems facing organ transplantation. Pigs are being developed as xenogeneic organ donors for use in humans. In this study, we propose a novel and simple method for tracheal intubation in a swine model using neuromuscular blocking agents and laryngeal mask airway...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28446226/xenotransplantation-of-interferon-gamma-pretreated-clumps-of-a-human-mesenchymal-stem-cell-extracellular-matrix-complex-induces-mouse-calvarial-bone-regeneration
#16
Kei Takeshita, Souta Motoike, Mikihito Kajiya, Nao Komatsu, Manabu Takewaki, Kazuhisa Ouhara, Tomoyuki Iwata, Katsuhiro Takeda, Noriyoshi Mizuno, Tsuyoshi Fujita, Hidemi Kurihara
BACKGROUND: Three-dimensional cultured clumps of a mesenchymal stem cell (MSC)/extracellular matrix (ECM) complex (C-MSC) consists of cells and self-produced ECM. C-MSC can regulate the cellular function in vitro and induce successful bone regeneration using ECM as a cell scaffold. Potentiating the immunomodulatory capacity of C-MSCs, which can ameliorate the allo-specific immune response, may be helpful in developing beneficial "off-the-shelf" cell therapy for tissue regeneration. It is well reported that interferon (IFN)-γ stimulates the immunosuppressive properties of MSC via upregulation of the immunomodulatory enzyme IDO...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#17
Nizar I Mourad, Claire Crossan, Victoria Cruikshank, Linda Scobie, Pierre Gianello
BACKGROUND: Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression levels can vary considerably between individuals and within different tissues of a single animal. In general, expression levels have been found to be particularly low in the pancreas compared to other porcine tissues suggesting a reduced risk associated with the use of this tissue...
April 26, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28437635/three-cysteine-residues-of-slc52a1-a-receptor-for-the-porcine-endogenous-retrovirus-a-perv-a-play-a-critical-role-in-cell-surface-expression-and-infectivity
#18
Winston Colon-Moran, Takele Argaw, Carolyn A Wilson
Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression...
April 20, 2017: Virology
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#19
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28433740/xenotransplantation-of-layer-by-layer-encapsulated-non-human-primate-islets-with-a-specified-immunosuppressive-drug-protocol
#20
Muhammad R Haque, Jiwoong Kim, Hyojun Park, Han Sin Lee, Kyo Won Lee, Taslim A Al-Hilal, Jee-Heon Jeong, Cheol-Hee Ahn, Doo Sung Lee, Sung Joo Kim, Youngro Byun
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with humans...
April 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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