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Abhijit Jagdale, David K C Cooper, Hayato Iwase, Robert S Gaston
Renal allotransplantation clearly offers better survival and quality of life for end-stage renal disease (ESRD) patients than chronic dialysis. The median waiting time for a deceased donor kidney in a suitable ESRD patient is 3.9 years. The initial candidates for pig kidney xenotransplantation will be those with ESRD unlikely to receive an allograft within a reasonable period of time. It is thus reasonable to ascertain whether clinical trials of xenotransplantation might likewise offer superior outcomes. Chronic dialysis in patients with ESRD is associated with poor quality of life, significant morbidity, and relatively high mortality, with only 56% surviving 3 years and 42% at 5 years...
November 20, 2018: Xenotransplantation
Jigesh A Shah, Madhukar S Patel, Nathan Louras, David H Sachs, Parsia A Vagefi
As outcomes in clinical liver transplantation steadily improve, demand continues to exceed supply, leading to a substantial disparity in organ availability. The translation of porcine liver xenotransplantation (LXT) into a clinical reality aims to address this dilemma. Our laboratory has previously established an applicable model of α-1,3-galactosyltransferase knockout (GalT-KO) pig-to-primate LXT with continuous human coagulation factor infusion and costimulation blockade. This report aims to further investigate the post-LXT lipid and amino acid metabolism profile in our longest surviving recipients (25 and 29 days)...
November 16, 2018: Xenotransplantation
Mengyu Gao, Yujia Wang, Yuting He, Yi Li, Qiong Wu, Guang Yang, Yanyan Zhou, Diwei Wu, Ji Bao, Hong Bu
The natural liver extracellular matrix (ECM) achieved by decellularization holds great potential in the fields of tissue engineering and regenerative medicine. Additionally, the use of crosslinking agents on the ECM to stabilize its ultrastructure and enhance scaffold durability is gaining interest in tissue engineering. The objective of this study was to compare the scaffold properties of porcine liver ECM crosslinked with different agents (glutaraldehyde, genipin, and quercetin) to find the best strategy for producing a decellularized matrix with optimal and stable characteristics for transplantation and regeneration...
November 10, 2018: Xenotransplantation
Abhijit Jagdale, Hayato Iwase, Edwin Klein, David K C Cooper
There is an increased incidence of certain tumors and other neoplastic disease in organ allotransplant recipients receiving immunosuppressive therapy. Following clinical pig organ xenotransplantation, will there be a risk of the development of neoplasia in the pig graft or in other tissues transplanted with it, eg, lymph nodes? The incidence of neoplasia in young slaughterhouse pigs is very low (<0.005%), but in older pigs is largely unknown (as most pigs are killed within the first six months of life). However, lymphosarcoma, nephroblastoma, and melanoma have been reported in pigs...
November 9, 2018: Xenotransplantation
Hiroki Okumura, Anna Nakanishi, Satoshi Toyama, Mai Yamanoue, Kana Yamada, Akane Ukai, Tadahiro Hashita, Takahiro Iwao, Tomomi Miyamoto, Yoh-Ichi Tagawa, Masumi Hirabayashi, Ichiro Miyoshi, Tamihide Matsunaga
The ultimate goal of regenerative medicine is the transplantation of a target organ generated by the patient's own cells. Recently, a method of organ generation using pluripotent stem cells (PSCs) and blastocyst complementation was reported. This approach is based on chimeric animal generation using an early embryo and PSCs, and the contribution of PSCs to the target organ is key to the method's success. However, the contribution rate of PSCs in target organs generated by different chimeric animal generation methods remains unknown...
October 30, 2018: Xenotransplantation
Adeline N Boettcher, Joan E Cunnick, Ellis J Powell, Timothy K Egner, Sara E Charley, Crystal L Loving, Christopher K Tuggle
BACKGROUND: Severe combined immunodeficient (SCID) pigs are an emerging animal model being developed for biomedical and regenerative medicine research. SCID pigs can successfully engraft human-induced pluripotent stem cells and cancer cell lines. The development of a humanized SCID pig through xenotransplantation of human hematopoietic stem cells (HSCs) would be a further demonstration of the value of such a large animal SCID model. Xenotransplantation success with HSCs into non-obese diabetic (NOD)-derived SCID mice is dependent on the ability of NOD mouse signal regulatory protein alpha (SIRPA) to bind human CD47, inducing higher phagocytic tolerance than other mouse strains...
October 12, 2018: Xenotransplantation
Avneesh K Singh, Joshua L Chan, Laura DiChiacchio, Naomi L Hardy, Philip C Corcoran, Billeta G T Lewis, Marvin L Thomas, Allen P Burke, David Ayares, Keith A Horvath, Muhammad M Mohiuddin
A combination of genetic manipulations of donor organs and target-specific immunosuppression is instrumental in achieving long-term cardiac xenograft survival. Recently, results from our preclinical pig-to-baboon heterotopic cardiac xenotransplantation model suggest that a three-pronged approach is successful in extending xenograft survival: (a) α-1,3-galactosyl transferase (Gal) gene knockout in donor pigs (GTKO) to prevent Gal-specific antibody-mediated rejection; (b) transgenic expression of human complement regulatory proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM) to avoid complement activation and coagulation dysregulation; and (c) effective induction and maintenance of immunomodulation, particularly through co-stimulation blockade of CD40-CD40L pathways with anti-CD40 (2C10R4) monoclonal antibody (mAb)...
October 5, 2018: Xenotransplantation
Marina Augusto Heuschkel, Amanda Leitolis, João Gabriel Roderjan, Paula Hansen Suss, César Augusto Oleinik Luzia, Francisco Diniz Affonso da Costa, Alejandro Correa, Marco Augusto Stimamiglio
Pericardial membrane derived from bovine heart tissues is a promising source of material for use in tissue-engineering applications. However, tissue processing is required for its use in humans due to the presence of animal antigens. Therefore, the purpose of this study was to evaluate the structural integrity and biocompatibility of the bovine pericardium (BP) after a soft decellularization process with a 0.1% sodium dodecyl sulfate (SDS) solution, with the aim to remove xenoantigens and preserve extracellular matrix (ECM) bioactivity...
September 28, 2018: Xenotransplantation
Nizar I Mourad, Pierre Gianello
Encapsulated porcine islets could be used to treat type I diabetes without necessitating severe immunosuppression. Islet survival and secretory function in the encapsulation device need to be preserved to ensure efficient insulin output in response to surrounding stimuli. In the present study, we evaluated stimulated insulin secretion from adult and neonatal pig islets seeded on an acellular collagen matrix and encapsulated in alginate during long-term culture. Pig islets survived longer and secreted more insulin when cultured on acellular porcine dermis compared to human fascia...
September 19, 2018: Xenotransplantation
Jong-Min Kim, Jun-Seop Shin, Sungyoung Han, Byoung-Hoon Min, Won Young Jeong, Ga Eul Lee, Min Sun Kim, Seeun Kwon, Hyunwoo Chung, Hee Jung Kang, Chung-Gyu Park
Pig-to-nonhuman primate (NHP) islet transplantation has been widely conducted as a preclinical xenotransplantation model prior to human clinical trial. Portal vein thrombosis is one of the complications associated with islet infusion through the portal vein into the liver. Here, we briefly report severe case of ascites formation accompanied by portal vein thrombi after pig-to-NHP islet xenotransplantation in a rhesus monkey. Meticulous prophylactic treatment such as continuous heparin infusion should be implemented to prevent portal vein thrombi in pig-to-NHP islet transplantation models...
September 8, 2018: Xenotransplantation
Song Lee, Soobin Moon, Ju Yun Oh, Eun Ha Seo, Yang Hee Kim, Eunsung Jun, In Kyoung Shim, Song Cheol Kim
BACKGROUND: Genetic reprogramming is a powerful method for altering cell properties and inducing differentiation. However, even if the same gene is reprogrammed, the results vary among cells. Therefore, a better possible strategy involves treating cells with factors that further stimulate differentiation while using stem cells with the same tissue origin. This study aimed to increase induction efficiency and insulin production in reprogrammed cells using a combination of factors that promote cell differentiation...
September 5, 2018: Xenotransplantation
Jinsoo Rhu, Kyo Won Lee, Kyeong Sik Kim, Ji Soo Lee, Sung Joo Kim, Jae Berm Park
We designed this study to define reference values of the cynomolgus monkey coagulation system, as the normal range of values has not been established. Measurement of coagulation function was determined by testing plasma samples from 30 healthy male cynomolgus monkeys. Prothrombin time (PT), PT activity, PT international normalized ratio (INR), activated prothrombin time (aPTT), antithrombin III activity, factor II, V, VII, VIII, IX, X, XI, and XII, protein C activity, protein S activity, and d-dimer were measured using standardized techniques...
September 5, 2018: Xenotransplantation
Lars Burdorf, Donald Harris, Siamak Dahi, Christopher Laird, Tianshu Zhang, Franchesca Ali, Aakash Shah, Mercedes Thompson, Gheorghe Braileanu, Xiangfei Cheng, Evelyn Sievert, Evan Schwartz, Selin Sendil, Dawn M Parsell, Emily Redding, Carol J Phelps, David L Ayares, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Elevated pulmonary vascular resistance (PVR), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on PVR, and their contribution to other lung xenograft injury mechanisms. METHODS: GalTKO.hCD46 single pig lungs were perfused ex vivo with fresh heparinized human blood: lungs were either treated with 1-Benzylimidazole (1-BIA) combined with histamine receptor blocker famotidine (n = 4) or diphenhydramine (n = 6), 1-BIA alone (n = 6) or were left untreated (n = 9)...
September 3, 2018: Xenotransplantation
Heather E Levy, Christopher Burlak
No abstract text is available yet for this article.
September 2018: Xenotransplantation
Wei Nie, Xiaoqian Ma, Cejun Yang, Zeyi Chen, Pengfei Rong, Minghua Wu, Jianhui Jiang, Mengqun Tan, Shounan Yi, Wei Wang
BACKGROUND: Hypoxia-induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord-derived MSC-conditioned medium (hu-MSC-CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia. METHODS: Neonatal porcine islet cell clusters were cultured with hu-MSC-CM, with or without exosomes, and native medium RPMI-1640 (Control) under hypoxic conditions (1% O2 )...
September 2018: Xenotransplantation
Hanchao Gao, Qing Zhang, Jicheng Chen, David K C Cooper, Hidetaka Hara, Pengfei Chen, Ling Wei, Yanli Zhao, Jia Xu, Zesong Li, Zhiming Cai, Shaodong Luan, Lisha Mou
Whether porcine cytokines are induced after pig-to-primate xenotransplantation and activate human cells remains unknown. First, we investigated the regulation of porcine IL-6, IFN-γ, IL-1β, and TNF-α in xenotransplantation using an in vitro model in which porcine aortic endothelial cells (PAECs) and porcine peripheral blood mononuclear cells (PBMCs) were stimulated with human serum. Downstream cytokines/chemokines were monitored. Pro-inflammatory cytokines (IL-6, IFN-γ, and IL-1β) and chemokines (IL-8, MCP-1, and CXCL2) were upregulated in the both cell types...
September 2018: Xenotransplantation
Angela Barone, John Benktander, Christy Whiddon, Chunsheng Jin, Cesare Galli, Susann Teneberg, Michael E Breimer
BACKGROUND: Pericardial tissue from various animal species is utilized for the production of the bioprosthetic heart valves (BHV) used clinically. Experimental data show that the eventual breakdown of BHV is partly due to immunological interactions with carbohydrate tissue antigens. To understand these processes, we have examined the glycolipid-based carbohydrate antigens in naïve porcine, bovine, and equine pericardia. EXPERIMENTAL: Total non-acid and acid glycosphingolipid fractions were isolated from porcine, bovine, and equine pericardia, and individual glycolipid compounds were characterized by thin-layer chromatography, mass spectrometry, and binding of monoclonal antibodies, lectins and bacteria in chromatogram binding assays...
September 2018: Xenotransplantation
Jong-Min Kim, Jaeyoung Kim, Se-Hyun Choi, Jun-Seop Shin, Byoung-Hoon Min, Won Young Jeong, Ga-Eul Lee, Min-Sun Kim, Seeun Kwon, Mee Kum Kim, Chung-Gyu Park
Tacrolimus-associated thrombotic microangiopathy (TA-TMA) is a rare complication. TA-TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage due to thrombus. We report asymptomatic TA-TMA diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation. Corneal transplantation had been conducted from a wild-type SNU miniature pig to a rhesus macaque. The veterinary records were retrospectively reviewed in this case. The immunosuppressive regimen consisted of rituximab, basiliximab, and IVIg as inductive therapies, and steroids with tacrolimus (0...
September 2018: Xenotransplantation
Yang Liu, Jing Zhang, Yingnan Zhang, Mingyang Yin, Sen Miao, Qingfeng Liang, Zhiqiang Pan
BACKGROUND: Descemet's membrane endothelial keratoplasty (DMEK) might be a promising technique for future xeno-corneal transplantation due to its ultrathin graft, extremely low rejection occurrence, suture-free graft fixation, and minimal immunosuppressive regime usage. The aim of this study is to explore the feasibility and efficacy of preparing porcine DMEK grafts by 2 techniques and investigate the graft ultrastructure. METHODS: Two mainstream techniques, mechanical stripping technique and liquid bubble technique, were modified to prepare the porcine DMEK grafts...
September 2018: Xenotransplantation
Kate E Smith, Robert C Johnson, Klearchos K Papas
There is currently a significant disparity between the number of patients who need lifesaving transplants and the number of donated human organs. Xenotransplantation is a way to address this disparity and attempts to enable the use of xenogeneic tissues have persisted for centuries. While immunologic incompatibilities have presented a persistent impediment to their use, encapsulation may represent a way forward for the use of cell-based xenogeneic therapeutics without the need for immunosuppression. In conjunction with modern innovations such as the use of bioprinting, incorporation of immune modulating molecules into capsule membranes, and genetic engineering, the application of xenogeneic cells to treat disorders ranging from pain to liver failure is becoming increasingly realistic...
September 2018: Xenotransplantation
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