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Xenotransplantation

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https://www.readbyqxmd.com/read/28730558/transplantation-sites-for-porcine-islets
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28699384/preclinical-safety-evaluation-of-allogeneic-ips-cell-based-therapy-in-a-swine-model-of-myocardial-infarction
#9
Carolina Gálvez-Montón, Carolina Soler-Botija, Oriol Iborra-Egea, Idoia Diaz-Guemes, Mercè Martí, Olalla Iglesias-Garcia, Cristina Prat-Vidal, Verónica Crisóstomo, Aida Llucià-Valldeperas, Isaac Perea-Gil, Santiago Roura, Francisco Miguel Sanchez Margallo, Ángel Raya, Antoni Bayés-Genís
The combination of biomatrices and induced pluripotent stem cell (iPSC) derivatives to aid repair and myocardial scar formation may soon become a reality for cardiac regenerative medicine. However, the tumor risk associated to residual undifferentiated cells remains an important safety concern of iPSC-based therapies. This concern is not satisfactorily addressed in xenotransplantation, which require immune suppression of the transplanted animal. Here, we assessed the safety of transplanting undifferentiated iPSC in an allogeneic setting...
July 12, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28698981/genetically-modified-pigs-as-organ-donors-for-xenotransplantation
#10
REVIEW
Magdalena Hryhorowicz, Joanna Zeyland, Ryszard Słomski, Daniel Lipiński
The growing shortage of available organs is a major problem in transplantology. Thus, new and alternative sources of organs need to be found. One promising solution could be xenotransplantation, i.e., the use of animal cells, tissues and organs. The domestic pig is the optimum donor for such transplants. However, xenogeneic transplantation from pigs to humans involves high immune incompatibility and a complex rejection process. The rapid development of genetic engineering techniques enables genome modifications in pigs that reduce the cross-species immune barrier...
July 11, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28693365/behavior-of-xeno-transplanted-undifferentiated-human-induced-pluripotent-stem-cells-is-impacted-by-microenvironment-without-evidence-of-tumors
#11
Veronica Martinez-Cerdeno, Bonnie Barrilleaux, Ashley McDonough, Jeanelle Ariza, Benjamin Yuen, Priyanka Somanath, Catherine Le, Craig Steward, Kayla Horton, Paul Knoepfler
Human pluripotent stem cells (hPSC) have great clinical potential via the use of their differentiated progeny, a population in which there is some concern over risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC. Preclinical studies using human stem cells are most often performed within a xenotransplant context. Here, we sought to measure how undifferentiated hPSC behave following xenotransplant. We directly transplanted undifferentiated human induced pluripotent and embryonic stem cells (hIPSC; hESC) into the adult mouse brain ventricle and analyzed their fates...
July 10, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28687929/periostin-promotes-ectopic-osteogenesis-of-ctla4-modified-bone-marrow-mesenchymal-stem-cells
#12
Fei Zhang, Zhigang Rong, Zhengdong Wang, Zehua Zhang, Dong Sun, Shiwu Dong, Jianzhong Xu, Fei Dai
The improved ectopic osteogenesis of cytotoxic T-lymphocyte-associated antigen 4-Ig-modified bone marrow mesenchymal stem cells (MSCs-CTLA4) has been demonstrated but the mechanisms involved remain to be determined. The extracellular matrix (ECM) has recently been reported to play a vital role in bone formation and periostin (POSTN) has been suggested as a key member in constructing the ECM in bone tissue. We found that POSTN expression in the MSCs-CTLA4 group is significantly enhanced compared with that in the MSCs group, not only in tissue-engineered bone (TEB) with femur heterotopic transplantation in vivo but also under the immune activation condition in vitro...
July 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28683478/-emergency-keratoplasty-with-porcine-xenografts-in-necrotizing-keratitis
#13
Galyna I Drozhzhyna, Tetiana B Gaidamaka, Claus Cursiefen, Björn O Bachmann, Olena V Ivanovska, Viktor L Ostashevsky, Boris M Kogan, Volodymyr J Usov, Natalija V Pasyechnikova
Background The great shortage of donor material in Ukraine makes it necessary to find additional sources of transplant material. A possible suitable material are the porcine corneas, as they are similar in structure and biomechanical parameters to the human cornea. The purpose of our study was to analyze the results of therapeutic keratoplasty (KP) with keratoxenotransplants from cryolyophilized porcine corneas in patients with severe necrotizing keratitis. Methods A retrospective analysis of 32 xenotransplantations patients with severe necrotizing keratitis (17 lamellar, 6 stepped perforating, 4 perforating, 5 "biological coverage" according to Puchkovskaya) was completed...
July 6, 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28679969/incidence-of-spontaneous-lymphomas-in-non-experimental-nod-shi-scid-il-2r%C3%AE-null-nog-mice
#14
Masahiko Yasuda, Tomoyuki Ogura, Takayuki Goto, Mika Yagoto, Yoko Kamai, Chie Shimomura, Nobuhito Hayashimoto, Yukito Kiyokawa, Hideki Shinohara, Riichi Takahashi, Kenji Kawai
Severely immunodeficient NOD/Shi-scid, IL-2Rγ(null) (NOG) mice provide an in vivo model for human cell/tissue transplantation studies. NOG mice were established by combining interleukin-2 receptor-γ chain knockout mice and NOD/Shi-scid mice. They exhibit a high incidence of thymic lymphomas and immunoglobulin (Ig) leakiness. In this study, we assessed the incidence of malignant lymphomas and the occurrence of leakiness in 2,184 non-experimental NOG retired breeder mice aged 16-40 weeks. We established that the total incidence of lymphomas was only 0...
July 6, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28677740/isoform-switch-of-cd44-induces-different-chemotactic-and-tumorigenic-ability-in-gallbladder-cancer
#15
Takeshi Miwa, Takuya Nagata, Hirofumi Kojima, Shinichi Sekine, Tomoyuki Okumura
Gallbladder cancer (GBC) is one of the most unfavorable prognostic tumor, and immediate growth and distant metastasis are important factors associated with the poor prognosis of patients with this disease. Standard and variant isoforms of CD44 are associated with tumor growth, metastasis, and epithelial-mesenchymal transition (EMT), although their roles in GBC are unclear. We investigated the relationship between the CD44 isoforms with EMT, chemotaxis, and tumorigenicity. We analyzed CD44 expression in the GBC cell line NOZ and found that it comprises a major population that expressed CD44std+/CD44v9- (CD44s) and the minor population that expressed CD44std-/CD44v9+ (CD44v)...
July 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28674022/fsip1-binds-her2-directly-to-regulate-breast-cancer-growth-and-invasiveness
#16
Tong Liu, Hao Zhang, Li Sun, Danyu Zhao, Peng Liu, Meisi Yan, Neeha Zaidi, Sudeh Izadmehr, Animesh Gupta, Wahid Abu-Amer, Minna Luo, Jie Yang, Xunyan Ou, Yining Wang, Xuefeng Bai, Yan Wang, Maria I New, Mone Zaidi, Tony Yuen, Caigang Liu
Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesis-related testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28670373/zeb2-promotes-tumor-metastasis-and-correlates-with-poor-prognosis-of-human-colorectal-cancer
#17
Ming-Zhe Li, Jing-Jing Wang, Shi-Bin Yang, Wen-Feng Li, Long-Bin Xiao, Yu-Long He, Xin-Ming Song
Colorectal cancer remains the most common cause of cancer-related deaths worldwide and it continues to lack an effective treatment. Here, we found that zinc finger E-box binding homeobox 2 (ZEB2) was overexpressed in several colorectal cancer cell lines and colorectal cancer specimens relative to adjacent non-cancerous tissues. Although ZEB2 has been reported to be associated with several tumors, its involvement in colorectal cancer progression remains unclear. In this study, we investigated the biological functions and molecular mechanisms of ZEB2 underlying colorectal carcinoma metastasis and angiogenesis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28667310/surface-modification-of-pig-endothelial-cells-with-a-branched-heparin-conjugate-improves-their-compatibility-with-human-blood
#18
Anjan K Bongoni, Evelyn Salvaris, Sofia Nordling, Nikolai Klymiuk, Eckhard Wolf, David L Ayares, Robert Rieben, Peetra U Magnusson, Peter J Cowan
Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with a glycocalyx-like layer and may inhibit (xeno)transplant-associated activation of the plasma cascade systems. Here, we investigated the use of CHC to protect WT and genetically modified (GTKO.hCD46.hTBM) pig aortic endothelial cells (PAEC) in two pig-to-human in vitro xenotransplantation settings. Model 1: incubation of untreated or hTNFα-treated PAEC with 10% human plasma induced complement C3b/c and C5b-9 deposition, cellular activation and coagulation activation in WT and GTKO...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28647700/molecular-proteomic-characterization-of-a-pediatric-medulloblastoma-xenograft
#19
George T Tsangaris, Konstantinos Dimas, Angeliki Malamou, Angeliki Katsafadou, Chrissa Papathanasiou, Dimitrios J Stravopodis, Constantinos E Vorgias, Maria Gazouli, Athanasios K Anagnostopoulos
BACKGROUND/AIM: Medulloblastoma (MBL), an archetypal primitive neuroectodermal tumor of the cerebellum, is the most common pediatric central nervous system malignancy representing approximately 20% of all childhood brain tumors. Herein, we report on a new xenotransplantable tumor cell line, derived from a 6-year-old female patient with cerebellar medulloblastoma, and the completele proteome molecular characterization of subsequent tumors from MBL xenotrasplanted mice. MATERIALS AND METHODS: Tumors were grown in nude mice as subcutaneous xenografts (MBLX) composed of small round cells with hyperchromatic nuclei and scant cytoplasm...
July 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#20
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
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