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Islet cell transplantation

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https://www.readbyqxmd.com/read/28186705/current-and-future-perspectives-on-alginate-encapsulated-pancreatic-islet
#1
Berit L Strand, Abba E Coron, Gudmund Skjak-Braek
Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long-term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long-term function of the graft in humans...
February 2, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174674/the-evaluation-of-islet-purification-methods-that-use-large-bottles-to-create-a-continuous-density-gradient
#2
Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi, Masayuki Matsushita, Hirofumi Noguchi
Islet purification is one of the most important steps of islet isolation for pancreatic islet transplantation. The most common method of islet purification is density gradient centrifugation using a COBE 2991 cell processor. However, this method can damage islets mechanically through its high shearing force. We recently reported that a new purification method using large plastic bottles effectively achieves a high yield of islets from the porcine pancreas. In the present study, we evaluated the methods of making a continuous density gradient...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28174291/local-sphingosine-kinase-1-activity-improves-islet-transplantation
#3
Darling Rojas-Canales, Daniella Penko, Kay K Myo Min, Kate A Parham, Heshan Peiris, Rainer V Haberberger, Stuart M Pitson, Chris Drogemuller, Damien J Keating, Shane T Grey, Patrick T Coates, Claudine S Bonder, Claire F Jessup
Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28169284/long-term-glycemic-control-in-adult-patients-undergoing-remote-vs-local-total-pancreatectomy-with-islet-autotransplantation
#4
Samuel J Kesseli, Matthew Wagar, Min K Jung, Kerrington D Smith, Yu Kuei Lin, R Matthew Walsh, Betul Hatipoglu, Martin L Freeman, Timothy L Pruett, Gregory J Beilman, David E R Sutherland, Ty B Dunn, David A Axelrod, Sushela S Chaidarun, Tyler K Stevens, Melena Bellin, Timothy B Gardner
OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013...
February 7, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28151049/effect-of-co-culture-of-mesenchymal-stem-stromal-cells-with-pancreatic-islets-on-viability-and-function-outcomes-a-systematic-review-and-meta-analysis
#5
Bianca Marmontel de Souza, Ana Paula Bouças, Fernanda Dos Santos de Oliveira, Karina Pires Reis, Patrícia Ziegelmann, Andrea Carla Bauer, Daisy Crispim
The maintenance of viable and functional pancreatic islets is crucial for successful islet transplantation from brain-dead donors. To overcome islet quality loss during culture, some studies have co-cultured islets with mesenchymal stem/stromal cells (MSC). However, it is still uncertain if MSC-secreted factors are enough to improve islet quality or if a physical contact between MSCs and islets is needed. Therefore, we performed a systematic review and meta-analysis to clarify the effect of different culture contact systems of islets with MSCs on viability and insulin secretion outcomes...
February 2, 2017: Islets
https://www.readbyqxmd.com/read/28150744/engineering-an-endocrine-neo-pancreas-by-repopulation-of-a-decellularized-rat-pancreas-with-islets-of-langerhans
#6
H Napierala, K-H Hillebrandt, N Haep, P Tang, M Tintemann, J Gassner, M Noesser, H Everwien, N Seiffert, M Kluge, E Teegen, D Polenz, S Lippert, D Geisel, A Reutzel Selke, N Raschzok, A Andreou, J Pratschke, I M Sauer, B Struecker
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135283/the-spleen-is-an-ideal-site-for-inducing-transplanted-islet-graft-expansion-in-mice
#7
Takeshi Itoh, Hitomi Nishinakamura, Kenjiro Kumano, Hiroyuki Takahashi, Shohta Kodama
Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP)...
2017: PloS One
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#8
Hayato Iwase, Hong Liu, Eva Schmelzer, Mohamed Ezzelarab, Martin Wijkstrom, Hidetaka Hara, Whayoung Lee, Jagjit Singh, Cassandra Long, Eric Lagasse, Jörg C Gerlach, David K C Cooper, Bruno Gridelli
BACKGROUND: Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28130838/production-of-high-quality-islets-from-goettingen-minipigs-choice-of-organ-preservation-solution-donor-pool-and-optimal-cold-ischemia-time
#9
Anja Steffen, Thomas Kiss, Janine Schmid, Undine Schubert, Sophie Heinke, Susann Lehmann, Stefan Bornstein, Barbara Ludwig, Stefan Ludwig
BACKGROUND: The transplantation of porcine islets into man might soon become reality for patients with type 1 diabetes mellitus. Therefore, porcine islets of high quality and quantity, and a scalable isolation process with strict quality control will be an unconditional prerequisite to enable the best possible transplantation graft. In this study, we provide a comparative study evaluating islet isolation outcome and in vitro survival based upon donor age, organ preservation solution (OPS), and cold ischemia time (CIT)...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28126963/plasma-derived-proteomic-biomarkers-in-hla-haploidentical-or-hla-matched-bone-marrow-transplantation-using-post-transplantation-cyclophosphamide
#10
Christopher G Kanakry, Giorgos Bakoyannis, Susan M Perkins, Shannon R McCurdy, Ante Vulic, Edus H Warren, Etienne Daguindau, Taylor Olmsted, Christen Mumaw, Andrea M H Towlerton, Kenneth R Cooke, Paul V O'Donnell, Heather J Symons, Sophie Paczesny, Leo Luznik
Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with HLA-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality...
January 25, 2017: Haematologica
https://www.readbyqxmd.com/read/28117444/interspecies-organogenesis-generates-autologous-functional-islets
#11
Tomoyuki Yamaguchi, Hideyuki Sato, Megumi Kato-Itoh, Teppei Goto, Hiromasa Hara, Makoto Sanbo, Naoaki Mizuno, Toshihiro Kobayashi, Ayaka Yanagida, Ayumi Umino, Yasunori Ota, Sanae Hamanaka, Hideki Masaki, Sheikh Tamir Rashid, Masumi Hirabayashi, Hiromitsu Nakauchi
Islet transplantation is an established therapy for diabetes. We have previously shown that rat pancreata can be created from rat pluripotent stem cells (PSCs) in mice through interspecies blastocyst complementation. Although they were functional and composed of rat-derived cells, the resulting pancreata were of mouse size, rendering them insufficient for isolating the numbers of islets required to treat diabetes in a rat model. Here, by performing the reverse experiment, injecting mouse PSCs into Pdx-1-deficient rat blastocysts, we generated rat-sized pancreata composed of mouse-PSC-derived cells...
February 9, 2017: Nature
https://www.readbyqxmd.com/read/28116870/multicomponent-injectable-hydrogels-for-antigen-specific-tolerogenic-immune-modulation
#12
Catia S Verbeke, Susana Gordo, David A Schubert, Sarah A Lewin, Rajiv M Desai, Jessica Dobbins, Kai W Wucherpfennig, David J Mooney
Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent immunotherapies to elicit immunity or reëstablish tolerance. Here, the authors explore the potential of an injectable, porous hydrogel to induce a regulatory T cell (Treg) response by delivering a peptide antigen to dendritic cells in a noninflammatory context. Two methods are described for delivering the BDC peptide from pore-forming alginate gels in the nonobese diabetic mouse model of type 1 diabetes: encapsulation in poly(lactide-co-glycolide) (PLG) microparticles, or direct conjugation to the alginate polymer...
January 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28104122/role-of-natural-killer-cells-in-the-innate-immune-system-after-intraportal-islet-transplantation-in-mice
#13
Y Saeki, K Ishiyama, N Ishida, Y Tanaka, H Ohdan
BACKGROUND: Both liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation. METHODS: To investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d(-/-) diabetic mice and NK cell-depleted CD1d(-/-) diabetic mice...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28101160/facile-mechanical-shaking-method-is-an-improved-isolation-approach-for-islet-preparation-and-transplantation
#14
Nina Yin, Tao Chen, Yuling Yu, Yongming Han, Fei Yan, Zhou Zheng, Zebin Chen
Successful islet isolation is crucial for islet transplantation and cell treatment for type 1 diabetes. Current isolation methods are able to obtain 500-1,000 islets per rat, which results in a waste of ≥50% of total islets. In the present study, a facile mechanical shaking method for improving islet yield (up to 1,500 per rat) was developed and summarized, which was demonstrated to be more effective than the existing well-established stationary method. The present results showed that isolated islets have a maximum yield of 1,326±152 when shaking for 15 min for the fully-cannulated pancreas...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28098405/shielding-engineered-islets-with-mesenchymal-stem-cells-enhance-survival-under-hypoxia
#15
Bhawna Chandravanshi, Ramesh Ramchandra Bhonde
In the present study we focused on the improvisation of islet survival in hypoxia.The Islet like cell aggregates (ICAs) derived from wharton's jelly mesenchymal stem cells (WJ MSC) were cultured with and without WJ MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin,Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitated highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#16
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28069642/alpha-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#17
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that alpha-1 antitrypsin (AAT, Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared to mice treated with saline...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28069641/differential-impact-of-chronic-hyperglycemia-on-humoral-versus-cellular-primary-alloimmunity
#18
Nicholas H Bishop, Michelle K Nelsen, K Scott Beard, Ronald G Gill
Diabetes is prevalent among solid organ transplant recipients and is universal among islet transplant recipients. While diabetes is often considered to result in an immune compromised state, the impact of chronic hyperglycemia on host alloimmunity is not clear. Potential immune modifying effects of obesity, autoimmunity, or diabetogenic agents like streptozotocin may confound understanding alloimmunity in experimental models of diabetes. Therefore, we sought to determine the role of chronic hyperglycemia due to insulinopenia on alloimmunity using the non-autoimmune, spontaneously diabetic H-2(b)-expressing C57BL/6 Ins2(Akita) mice (Akita)...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28066985/from-micro-to-macro-the-hierarchical-design-in-a-micropatterned-scaffold-for-cell-assembling-and-transplantation
#19
Kai Wang, Xi Wang, Chengsheng Han, Wenda Hou, Jinyang Wang, Liangyi Chen, Ying Luo
A microwell-patterned membranous scaffold that integrates nano- and microscale topographical characteristics based on polyurethane is fabricated for transplanting syngeneic islets and allogeneic mesenchymal stem cells into diabetic rodents. The scaffold effectively allows for assembling of single cells/microtissues, enables the transplantation of cells with spatial control, and improves the transplant's engraftment efficacy in vivo for treating diabetes.
January 2017: Advanced Materials
https://www.readbyqxmd.com/read/28058779/dual-role-of-il-1%C3%AE-in-islet-amyloid-formation-and-its-%C3%AE-cell-toxicity-implications-in-type-2-diabetes-and-islet-transplantation
#20
Yoo Jin Park, Garth L Warnock, Ziliang Ao, Nooshin Safikhan, Mark Meloche, Ali Asadi, Timothy J Kieffer, Lucy Marzban
AIMS/HYPOTHESIS: Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to β-cell failure in type 2 diabetes, cultured and transplanted islets. We previously showed that biosynthetic hIAPP aggregates induce β-cell Fas upregulation and activation of the Fas apoptotic pathway. Here, we used cultured human and hIAPP-expressing mouse islets to investigate: (1) the role of IL-1β in amyloid-induced Fas upregulation; (2) the effects of IL-1β-induced β-cell dysfunction on proIAPP processing and amyloid formation...
January 6, 2017: Diabetes, Obesity & Metabolism
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