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https://www.readbyqxmd.com/read/29777589/low-adhesive-ethylene-vinyl-alcohol-based-packaging-to-xenogeneic-islets-encapsulation-for-type-1-diabetes-treatment
#1
Kai-Chiang Yang, Goichi Yanai, Sin-Yu Yang, Priyadarshini Canning, Yoshio Satou, Masako Kawagoe, Shoichiro Sumi
Transplantation of encapsulated porcine islets is proposed to treat type 1 diabetes. However, envelopment of fibrous tissue and infiltration of immune cells impair islets function and eventually cause implant failure. It is known that hemodialysis using an ethylene vinyl alcohol (EVOH) membrane results in minor tissue responses. Therefore, we hypothesized that using a low adhesive EVOH membrane for encapsulation may prevent host cell accumulation and fibrous capsule formation. In this study, rat islets suspended in chitosan gel were encapsulated in bags made from highly porous EVOH membranes, and their in vitro insulin secretion function as well as in vivo performance were evaluated...
May 19, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29757700/adhesion-characteristics-of-porcine-pancreatic-islets-and-exocrine-tissue-to-coating-materials
#2
Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Since the report of the Edmonton protocol in 2000, islet transplantation has been implemented worldwide, and xenotransplantation using porcine islets has also been reported. In addition, many basic experiments using pancreatic islets and exocrine tissue after isolation have been reported. Recently, exocrine cells have been found to be essential for inducing the differentiation of pancreatic islets. Therefore, the importance of the culture conditions for pancreatic tissue when conducting experiments using pancreatic tissue is also increasing...
May 14, 2018: Islets
https://www.readbyqxmd.com/read/29691708/generation-of-insulin-deficient-piglets-by-disrupting-ins-gene-using-crispr-cas9-system
#3
Bumrae Cho, Su Jin Kim, Eun-Jin Lee, Sun Mi Ahn, Jin Seok Lee, Dal-Young Ji, Kiho Lee, Jung-Taek Kang
Diabetes mellitus is a chronic disease with accompanying severe complications. Various animal models, mostly rodents due to availability of genetically modified lines, have been used to investigate the pathophysiology of diabetes. Using pigs for diabetic research can be beneficial because of their similarity in size, pathogenesis pathway, physiology, and metabolism with human. However, the use of pigs for diabetes research has been hampered due to only few pig models presenting diabetes symptoms. In this study, we have successfully generated insulin-deficient pigs by generating the indels of the porcine INS gene in somatic cells using CRISPR/Cas9 system followed by somatic cell nuclear transfer...
April 24, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29550793/orexin-a-modulates-endocrine-function-and-viability-of-porcine-pancreatic-islets
#4
M Sassek, E Pruszynska-Oszmalek, K W Nowak
The physiology of porcine pancreatic islets is poorly understood. Orexin A is one of important agents regulating the physiology of porcine pancreatic islets. This study aimed to determine the potential effect of orexin A on the functioning of porcine pancreatic islets. Orexin receptor localization was done by PCR (polymerase chain reaction) and Western Blot, both in pancreatic isolated islets and whole pancreas. Secretion of insulin and glucagon from islets after orexin-A treatment was assayed. The viability of pig pancreatic islet cells and level of cleaved/total caspase 3 protein were measured by MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Western blotting, respectively...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29517421/development-of-a-polarized-pancreatic-ductular-cell-epithelia-for-physiological-studies
#5
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29427659/construction-of-emsc-islet-co-localizing-composites-for-xenogeneic-porcine-islet-transplantation
#6
Jung-Sik Kim, Hyunwoo Chung, Nari Byun, Seong-Jun Kang, Sunho Lee, Jun-Seop Shin, Chung-Gyu Park
Pancreatic islet transplantation is an ultimate solution for treating patients with type 1 diabetes (T1D). The pig is an ideal donor of islets for replacing scarce human islets. Besides immunological hurdles, non-immunological hurdles including fragmentation and delayed engraftment of porcine islets need solutions to succeed in porcine islet xenotransplantation. In this study, we suggest a simple but effective modality, a cell/islet co-localizing composite, to overcome these challenges. Endothelial-like mesenchymal stem cells (EMSCs), differentiated from bone-marrow derived mouse mesenchymal stem cells (MSCs), and MSCs evenly coated the surface of porcine islets (>85%) through optimized culture conditions...
March 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29401607/mscs-promote-the-development-and-improve-the-function-of-neonatal-porcine-islet-grafts
#7
Sirong He, Chengshi Wang, Xiaojiong Du, Younan Chen, Jiuming Zhao, Bole Tian, Huimin Lu, Yi Zhang, Jingping Liu, Guang Yang, Lan Li, Hongxia Li, Jingqiu Cheng, Yanrong Lu
Deficient insulin secretion caused by immaturity is the predominant disadvantage of neonatal porcine islets (NPIs) when they serve as a source for islet xenotransplantation. We hypothesize that the transplantation of NPIs with a combination of mesenchymal stem cells (MSCs) can accelerate NPI maturation and improve the engraftment and function of NPIs. After indirect coculturing with monkey MSCs over 21 d, insulin secretion and the expression of regulatory genes relevant to development were assessed in NPIs...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29372538/sustained-exenatide-delivery-via-intracapsular-microspheres-for-improved-survival-and-function-of-microencapsulated-porcine-islets
#8
Benjamin Lew, In-Yong Kim, Hyungsoo Choi, Kyekyoon Kevin Kim
The ability of glucagon-like peptide-1 analogs to enhance glucose-dependent insulin secretion and to inhibit β cell apoptosis could be of potential benefit for islet transplantation. In this study, we investigated the effect of sustained local delivery of exenatide, a synthetic exendin-4, on the in vitro viability and function of encapsulated porcine islets. Prior to encapsulation, we fabricated exenatide-loaded poly(latic-co-glycolic acid) microspheres, and investigated their release behavior with different initial drug-loading amounts...
January 25, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29359356/the-value-of-glycated-albumin-for-the-prediction-of-graft-outcome-in-the-non-human-primate-porcine-islet-transplantation-model
#9
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Jun-Seop Shin, Chung-Gyu Park
BACKGROUND: The development of a precise and easy-to-use tool for monitoring islet graft function is important in clarifying the causes of graft loss, identifying appropriate therapy, and ensuring graft survival in the nonhuman primate (NHP) model of porcine islet transplantation (PITx). Glycated albumin (GA) is an indicator of intermediate-term changes in blood glucose control and is useful in clinical diabetes management. The validity of GA for monitoring graft function in NHP recipients of PITx was evaluated using a retrospective analysis of cohort samples...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29322561/effect-of-an-oxygen-generating-scaffold-on-the-viability-and-insulin-secretion-function-of-porcine-neonatal-pancreatic-cell-clusters
#10
Eun Mi Lee, Ji-In Jung, Zahid Alam, Hee-Gyeong Yi, Heejin Kim, Jin Woo Choi, Sunghoon Hurh, Young June Kim, Jong Cheol Jeong, Jaeseok Yang, Kook-Hwan Oh, Hee Chan Kim, Byeong Chun Lee, Inho Choi, Dong-Woo Cho, Curie Ahn
BACKGROUND: Islet encapsulation techniques have shown limited success in maintaining islet survival and function because encapsulation decreases oxygen supply. In this study, an oxygen-generating scaffold was fabricated to prevent hypoxic cell damage and improve the viability and insulin secretion of islets. METHODS: We fabricated an oxygen-generating scaffold by mixing calcium peroxide (CaO2 ) with polydimethylsiloxane (PDMS). We evaluated the effects of the oxygen-generating PDMS + CaO2 scaffold on viability, caspase-3 and caspase-7 activity, oxygen consumption rate (OCR), glucose-stimulated insulin secretion (GSIS), hypoxic cell marker expression, and reactive oxygen species (ROS) levels in porcine neonatal pancreatic cell clusters (NPCCs)...
January 10, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29218794/examining-the-potential-for-porcine-derived-islet-cells-to-harbour-viral-pathogens
#11
Claire Crossan, Zoe O'Hara, Nizar Mourad, Pierre Gianello, Linda Scobie
With an onus on safety in the potential use of porcine islet cells as a treatment for diabetes, the use of animals lacking exogenous pathogens is clearly important and multilevel screening strategies have been presented on testing animals and the product. In this study, we wished to investigate whether islet cells indeed harboured the same viral pathogens of concern in the source animal. PMBC and islet cells from both adult and neonatal source animals were directly compared and tested for PCMV, PLHV, PCV2, PPV and HEV using both molecular and serological assays...
December 7, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29215800/microencapsulation-for-cell-therapy-of-type-1-diabetes-mellitus-the-interplay-between-common-beliefs-prejudices-and-real-progress
#12
EDITORIAL
Riccardo Calafiore
Critical discussion on pancreatic islets/insulin producing cells microencapsulation within highly purified alginic acid-derived bioplymers: past, present and future.
March 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29178588/early-barriers-to-neonatal-porcine-islet-engraftment-in-a-dual-transplant-model
#13
K P Samy, R P Davis, Q Gao, B M Martin, M Song, J Cano, A B Farris, A McDonald, E K Gall, C R Dove, F V Leopardi, T How, K D Williams, G R Devi, B H Collins, A D Kirk
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology...
November 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29159187/the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#14
REVIEW
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29135052/enhanced-effect-of-human-mesenchymal-stem-cells-expressing-human-tnf-%C3%AE-r-fc-and-ho-1-gene-on-porcine-islet-xenotransplantation-in-humanized-mice
#15
Han-Sin Lee, Sanghyun Song, Du Yeon Shin, Geun-Soo Kim, Jong-Hyun Lee, Chan Woo Cho, Kyo Won Lee, Hyojun Park, Curie Ahn, Jaeseok Yang, Heung-Mo Yang, Jae Berm Park, Sung-Joo Kim
BACKGROUND: Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood-Mediated Inflammatory Reaction (IBMIR), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor-ɑ receptor type I (sTNF-αR) and heme oxygenase (HO)-1 genes (HO-1/sTNF-αR) have been shown to improve the viability and functionality of porcine islets after transplantation...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#16
Xiaoqian Ma, Cejun Yang, Juan Zhang, Jia Wang, Wei Li, Chang Xu, Pengfei Rong, Bin Ye, Minghua Wu, Jianhui Jiang, Shounan Yi, Wei Wang
BACKGROUND: Neonatal pig islet-like cell clusters (NICC) are an attractive source of insulin-producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC after their transplantation due to apoptosis resulted from islet isolation and instant blood-mediated inflammatory reaction remains to be overcome. METHODS: EGM2 medium depleted with hydrocortisone and supplemented with 50 mmol/L isobutylmethylxanthine, 10 mmol/L nicotinamide, and 10 mmol/L glucose was used to culture NICC at day 1, the day after isolation and changed every other day...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29099648/a-proteome-analysis-of-pig-pancreatic-islets-and-exocrine-tissue-by-liquid-chromatography-with-tandem-mass-spectrometry
#17
Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a proteome analysis method, and the shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolving power. In this study, we analyzed the protein expression in pancreatic tissue by LC-MS/MS. Islets isolated from porcine pancreata (purity ≥95%) and exocrine tissue (purity ≥99%) were used in this study. LC-MS/MS showed that 13 proteins were expressed in pancreatic islets only (Group I), 43 proteins were expressed in both islets and exocrine tissue (Group I&E), and 102 proteins were expressed in exocrine tissue only (Group E)...
November 2, 2017: Islets
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#18
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#19
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/28963731/ex-vivo-expanded-baboon-cd39-regulatory-t-cells-prevent-rejection-of-porcine-islet-xenografts-in-nod-scid-il-2r%C3%AE-mice-reconstituted-with-baboon-peripheral-blood-mononuclear-cells
#20
Dandan Huang, Ya Wang, Wayne J Hawthorne, Min Hu, Joanne Hawkes, Heather Burns, Sussan Davies, Feng Gao, Yi Vee Chew, Shounan Yi, Philip J O'Connell
BACKGROUND: A high immunosuppressive burden is required for long-term islet xenograft survival in non-human primates even using genetically modified donor pigs. AIMS: We aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation. MATERIALS & METHODS: Baboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells (PBMC) were characterized by cell phenotyping and suppressive activity assays in vitro...
November 2017: Xenotransplantation
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