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Xenotransplantation

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'Dirty pigs' and the xenotransplantation paradox.

Gill Haddow,

For almost the last 300 years human beings have sought to use organs from non-human animals to repair or replace their own failing organs. This procedure of intraspecies transplant is called xenotransplantation, and despite the continued attempts by researchers, it is yet to be successful. Experiments in xenotransplantation persist, however, ... Read more >>

Med Humanit (Medical humanities)
[2021, :]

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MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκBα negative feedback loop.

Lili Jiang, Chuyong Lin, Libing Song, Jueheng Wu, Baixue Chen, Zhe Ying, Lishan Fang, Xiao Yan, Mian He, Jun Li, Mengfeng Li,

J Clin Invest (The Journal of clinical investigation)
[2021, 131(22):]

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Immunosuppressive Potential of Activated Human Amniotic Cells in an Experimental Murine Model of Skin Allo- and Xenotransplantation.

Emanuel Kolanko, Aniela Grajoszek, Piotr Czekaj,

Isolated human amniotic cells (hAC) could be used as a source of immunomodulatory factors in regenerative medicine and transplantation. However, in previous experimental studies, native hAC administered to skin graft recipients did not induce graft immunotolerance. To strengthen the immunomodulatory properties of hAC prior to administration to the recipient, we ... Read more >>

Front Med (Lausanne) (Frontiers in medicine)
[2021, 8:715590]

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Updateon xenotransplantation for May/June 2021.

Wayne J Hawthorne, Erin Fuller, Adwin Thomas, Joseph Sushil Rao, Christopher Burlak,

Xenotransplantation (Xenotransplantation)
[2021, 28(5):e12710]

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Addressing Concerns toward Xenotransplantation

Daniel Hurst, Lluz Padilla, Wayne Paris, David Cooper, David Cleveland,

There is increasing attention being given toward social and ethical implications of xenotransplantation that may begin relatively soon. IN a recent commentary by Loebe and Parker, the authors address many of the social and ethical issues in regard to xenotransplantation, but do so only superficially. This letter to the editor ... Read more >>

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Adult Pig Islet Isolation.

Ying Lu, Zuhui Pu, Jiao Chen, Jing Deng, Ying Deng, Shufang Zhu, Chunliang Xu, Fuwen Yao, Zijing Wu, Yong Ni, Yongqiang Zhan, Jun Cheng, Naiyang Zhan, Wenlong Huang, Zhiming Cai, Rita Bottino, Lisha Mou,

Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of pancreatic β cells, which results in little or no insulin production. Islet transplantation plays an important role in the treatment of T1DM, with the improved glycometabolic control, the reduced progression of complications, the reduction of hypoglycemic episodes when compared ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2021, (176):]

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Development and characterization of Gal KO porcine bone marrow-derived mesenchymal stem cells.

Takeshi Kikuchi, Masuhiro Nishimura, Maki Hirata, Fuminori Tanihara, Natsuki Komori, Makoto Tanaka, Osamu Sawamoto, Takeshige Otoi, Shinichi Matsumoto,

<h4>Background</h4>We demonstrated that neonatal porcine bone marrow-derived mesenchymal stem cell (npBM-MSCs) could improve a critical ischemic limb disease in rat model more efficiently compared with human MSCs. However, since porcine MSC presents galactosyl-alpha 1,3-galactose antigen (Gal antigen), MSC could be eliminated by the xenogeneic rejection. Recently, we established Gal knockout ... Read more >>

Xenotransplantation (Xenotransplantation)
[2021, :e12717]

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Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.

Margaret R Connolly, Kasinath Kuravi, Lars Burdorf, Lori Sorrells, Benson Morrill, Arielle Cimeno, Todd Vaught, Amy Dandro, Selin Sendil, Zahra A Habibabady, Jeffery Monahan, Tiezheng Li, John LaMattina, Willard Eyestone, David Ayares, Carol Phelps, Agnes M Azimzadeh, Richard N Pierson,

The transplantation of organs across species offers the potential to solve the shortage of human organs. While activation of human platelets by human von Willebrand factor (vWF) requires vWF activation by shear stress, contact between human platelets and porcine vWF (pvWF) leads to spontaneous platelet adhesion and activation. This non-physiologic ... Read more >>

Xenotransplantation (Xenotransplantation)
[2021, :e12712]

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Minimizing Ischemia Reperfusion Injury in Xenotransplantation.

Parth M Patel, Margaret R Connolly, Taylor M Coe, Anthony Calhoun, Franziska Pollok, James F Markmann, Lars Burdorf, Agnes Azimzadeh, Joren C Madsen, Richard N Pierson,

The recent dramatic advances in preventing "initial xenograft dysfunction" in pig-to-non-human primate heart transplantation achieved by minimizing ischemia suggests that ischemia reperfusion injury (IRI) plays an important role in cardiac xenotransplantation. Here we review the molecular, cellular, and immune mechanisms that characterize IRI and associated "primary graft dysfunction" in allotransplantation ... Read more >>

Front Immunol (Frontiers in immunology)
[2021, 12:681504]

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Early Interferon-Gamma Response in Nonhuman Primate Recipients of Solid-Organ Xenotransplantation.

Eun Mi Park, Haneulnari Lee, Hee Jung Kang, Keon Bong Oh, Jun Seok Kim, Hyun Keun Chee, Jung-Hwan Park, Kyoung Sik Park, Ik-Jin Yun,

To understand changes in biological responses in nonhuman primate (NHP) recipients of xenotransplantation (XTP), we retrospectively investigated chronological changes in cytokine profiles of NHP recipients after solid-organ XTP. Plasma samples were collected from 7 NHP recipients of pig heart or kidney XTP with α-1,3-galactosyltransferase gene knockout (GTKO) under anti-CD154-based immune suppression ... Read more >>

Transplant Proc (Transplantation proceedings)
[2021, :]

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Comparison between slow and rapid freezing for adrenal gland cryopreservation and xenotransplantation.

Li Shasha, Li Zhongjie, Fan Lingling, V D Ustichenko, O V Pakhomov, Bo Deng,

The aim of our study was to examine whether slow or rapid cryopreservation of adrenal xenografts affected xenotransplant outcome. Adrenal xenografts were got from newborn piglets (<24 h after birth). Receptor rats were randomly divided into four groups: a bilateral adrenalectomy group, fresh xenotransplantation group, rapid cryopreservation xenotransplantation group, and a ... Read more >>

Cryobiology (Cryobiology)
[2021, 102:68-75]

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"You cannot stay in the laboratory forever"*: Taking pig kidney xenotransplantation from the laboratory to the clinic.

David K C Cooper, Hidetaka Hara,

Progress in life-supporting kidney transplantation in the genetically-engineered pig-to-nonhuman primate model has been encouraging, with pig kidneys sometimes supporting life for > 1 year. What steps need to be taken by (i) the laboratory team, and (ii) the clinical team to prepare for the first clinical trial? The major topics include ... Read more >>

EBioMedicine (EBioMedicine)
[2021, 71:103562]

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m6A-mediated upregulation of AC008 promotes osteoarthritis progression through the miR-328-3p‒AQP1/ANKH axis.

Jiashu Yang, Ming Zhang, Dawei Yang, Yunfei Ma, Yuting Tang, Mengying Xing, Lingyun Li, Li Chen, Yucui Jin, Changyan Ma,

Long noncoding RNAs (lncRNAs) have emerged as important regulators of osteoarthritis (OA), but the biological roles and clinical significance of most lncRNAs in OA are not fully understood. Microarray analysis was performed to identify differentially expressed lncRNAs, mRNAs, and miRNAs between normal and osteoarthritic cartilage. We found that AC008440.5 (abbreviated ... Read more >>

Exp Mol Med (Experimental & molecular medicine)
[2021, :]

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Organ transplants of the future: planning for innovations including xenotransplantation.

Emanuele Cozzi, Stefan Schneeberger, Maria Irene Bellini, Erik Berglund, Georg Böhmig, Kevin Fowler, Martin Hoogduijn, Ina Jochmans, Georg Marckmann, Lorna Marson, James Neuberger, Rainer Oberbauer, Richard N Pierson, Bruno Reichart, Linda Scobie, Colin White, Maarten Naesens, ,

The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to cell, tissue and solid organ xenotransplants have been obtained from many animal models utilizing genetic engineering and protocols of pathogen-free husbandry. Findings have reached a tipping point, and xenotransplantation ... Read more >>

Transpl Int (Transplant international : official journal of the European Society for Organ Transplantation)
[2021, :]

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Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig-to-baboon xenotransplantation.

Kazuhiro Takeuchi, Yuichi Ariyoshi, Akira Shimizu, Yuichiro Okumura, Gabriel Cara-Fuentes, Gabriela E Garcia, Thomas Pomposelli, Hironosuke Watanabe, Lennan Boyd, Dilrukshi K Ekanayake-Alper, Dasari Amarnath, Megan Sykes, David H Sachs, Richard J Johnson, Kazuhiko Yamada,

<h4>Background</h4>Nephrotic syndrome is a common complication of pig-to-baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down-regulation of SMPDL-3b in glomeruli have an important role in the development of proteinuria following pig-to-baboon KXTx. Recently we found induced expression of human CD47 (hCD47) on ... Read more >>

Xenotransplantation (Xenotransplantation)
[2021, :]

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Correction to: Cardiac xenotransplantation: a promising way to treat advanced heart failure.

Songren Shu, Jie Ren, Jiangping Song,

Heart Fail Rev (Heart failure reviews)
[2021, 26(6):1527]

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Pathways to Clinical Cardiac Xenotransplantation.

Bruno Reichart, Matthias Längin, Joachim Denner, Reinhard Schwinzer, Peter J Cowan, Eckhard Wolf,

Heart transplantation is the only long-lasting lifesaving option for patients with terminal cardiac failure. The number of available human organs is however far below the actual need, resulting in substantial mortality of patients while waiting for a human heart. Mechanical assist devices are used to support cardiac function but are ... Read more >>

Transplantation (Transplantation)
[2021, 105(9):1930-1943]

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Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation.

Andrew B Adams, Brendan P Lovasik, David A Faber, Christopher Burlak, Cynthia Breeden, Jose L Estrada, Luz M Reyes, Rodrigo M Vianna, Matthew F Tector, Alfred J Tector,

<h4>Objective</h4>Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression.<h4>Methods</h4>Double (Gal and Sda) and triple ... Read more >>

Ann Surg (Annals of surgery)
[2021, 274(3):473-480]

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Suggested Patient Selection Criteria for Initial Clinical Trials of Pig Kidney Xenotransplantation in the United States.

Abhijit Jagdale, Vineeta Kumar, Douglas J Anderson, Jayme E Locke, Michael J Hanaway, Devin E Eckhoff, Hayato Iwase, David K C Cooper,

Transplantation (Transplantation)
[2021, 105(9):1904-1908]

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Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons.

Jeremy B Foote, Abhijit Jagdale, Takayuki Yamamoto, Hidetaka Hara, Mohamed H Bikhet, Henk-Jan Schuurman, Huy Q Nguyen, Mohamed Ezzelarab, David Ayares, Douglas J Anderson, Huma Fatima, Devin E Eckhoff, David K C Cooper, Hayato Iwase,

<h4>Introduction</h4>Pigs deficient in three glycosyltransferase enzymes (triple-knockout [TKO] pigs, that is, not expressing the three known carbohydrate xenoantigens) and expressing 'protective' human transgenes are considered a likely source of organs for transplantation into human recipients. Some human sera have no or minimal natural antibody binding to red blood cells (RBCs) ... Read more >>

Xenotransplantation (Xenotransplantation)
[2021, :]

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Macroautophagy supports Sonic Hedgehog signaling by promoting Patched1 degradation.

Xin Yang, Nan Jin, Yu Wang, Yixing Yao, Yue Wang, Tianyuan Li, Chen Liu, Tingting Yu, Hao Yin, Ziyu Zhang, Steven Y Cheng, Shen Yue,

Autophagy is a highly conservative self-digestion process to maintain intracellular homeostasis and to ensure the survival of cells under stress. Activation of Sonic Hedgehog (Shh) signaling depends on the normal endocytic degradation of pathway receptor Patched1 (Ptch1). It is unclear whether autophagy participates in the receptor endocytosis and modulates Shh ... Read more >>

Biochim Biophys Acta Mol Cell Res (Biochimica et biophysica acta. Molecular cell research)
[2021, 1868(12):119124]

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Addressing concerns toward xenotransplantation.

Daniel J Hurst, Luz Padilla, Wayne Paris, David K C Cooper, David C Cleveland,

J Card Surg (Journal of cardiac surgery)
[2021, 36(12):4821]

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ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.

María Victoria Castro, Gastón Alexis Barbero, María Belén Villanueva, Luca Grumolato, Jérémie Nsengimana, Julia Newton-Bishop, Edith Illescas, María Josefina Quezada, Pablo Lopez-Bergami,

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Gain and loss-of-function strategies were applied to study the biological function ... Read more >>

J Biomed Sci (Journal of biomedical science)
[2021, 28(1):76]

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Porcine-derived medical therapies for SARS-CoV-2: Traversing Muslim bioethical concerns and assuring equity.

Aasim I Padela,

Xenotransplantation (Xenotransplantation)
[2021, :e12714]

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New rat to mouse xenograft transplantation of endometrium as a model of human endometriosis.

Amir Abdolmaleki, Cyrus Jalili, Kamran Mansouri, Mitra Bakhtiari,

<h4>Background</h4>Endometriosis can lead to infertility. Since there is no definitive treatment for endometriosis, animal modelling seems necessary to examine the possible treatments. Mouse endometrium cannot be separated for endometriosis induction. In addition, transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage. In this study, we defined ... Read more >>

Animal Model Exp Med (Animal models and experimental medicine)
[2021, 4(3):268-277]

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