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Islet cell transplantation

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https://www.readbyqxmd.com/read/28101160/facile-mechanical-shaking-method-is-an-improved-isolation-approach-for-islet-preparation-and-transplantation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28017506/insulin-producing-cells-generation-by-overexpression-of-mir-375-in-adipose-derived-mesenchymal-stem-cells-from-diabetic-patients
#8
Mehran Piran, Seyed Ehsan Enderami, Mehrdad Piran, Hadis Soltani Sedeh, Ehsan Seyedjafari, Abdolreza Ardeshirylajimi
Diabetes Mellitus (DM) is a systematic disease, which happens because of destruction of islets of Langerhans in the pancreas and systematic resistance to insulin. The lack of donor for pancreas transplantation and risk of transplant rejection is the main challenge in the treatment of this disease. Stem cells are proper and sufficient source for creating insulin-producing cells (IPC). In this study adipose tissue was provided from diabetic patients operated for liposuction and then adipose derived stem cells (ADSCs) were isolated, characterized and then treated by lentiviruses containing miR-375, after 7, 14 and 21 days of induction, islet-like clusters (ILC) specific genes including insulin and PDX1 were evaluated by Real Time RT-PCR...
December 22, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28008169/advances-in-islet-encapsulation-technologies
#9
Tejal Desai, Lonnie D Shea
Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans...
December 23, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28006437/does-exercise-pose-a-challenge-to-glucoregulation-after-clinical-islet-transplantation
#10
Deanna R Funk, Normand G Boulé, Peter A Senior, Jane E Yardley
Islet transplantation (ITx) is effective in preventing severe hypoglycemia by restoring glucose-dependent insulin secretion in type 1 diabetes (T1D), but may not normalize glucose regulation. Studies suggest that physical activity plays a role in maintaining β-cell mass and function in individuals with type 2 diabetes and animal models of diabetes. This could indicate that physical activity plays a role in graft survival in ITx recipients. This review's objective is to assess current knowledge related to physical activity in ITx recipients...
January 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28003935/aggregation-of-engineered-human-%C3%AE-cells-into-pseudoislets-insulin-secretion-and-gene-expression-profile-in-normoxic-and-hypoxic-milieu
#11
Marie-José Lecomte, Séverine Pechberty, Cécile Machado, Sandra Da Barroca, Philippe Ravassard, Raphaël Scharfmann, Paul Czernichow, Bertrand Duvillié
Innovative treatments to cure type 1 diabetes are being actively researched. Among the different strategies, the replacement of β-cells has given promising results. Classically, islets from cadaveric donors are transplanted into diabetic patients, but recently phase I clinical trials that use stem cell-derived β-cells have been started. Such protocols require either an immunosuppressive treatment or the macroencapsulation of the β-cells. They involve cell aggregation and the exposure of the cells to hypoxia...
December 3, 2016: Cell Medicine
https://www.readbyqxmd.com/read/27999871/loss-of-prohormone-convertase-2-promotes-beta-cell-dysfunction-in-a-rodent-transplant-model-expressing-human-pro-islet-amyloid-polypeptide
#12
Jaques A Courtade, Evan Y Wang, Paul Yen, Derek L Dai, Galina Soukhatcheva, Paul C Orban, C Bruce Verchere
AIMS/HYPOTHESIS: A contributor to beta cell failure in type 2 diabetes and islet transplants is amyloid formation by aggregation of the beta cell peptide, islet amyloid polypeptide (IAPP). Similar to the proinsulin processing pathway that generates insulin, IAPP is derived from a prohormone precursor, proIAPP, which requires cleavage by prohormone convertase (PC) 1/3 and PC2 in rodent pancreatic beta cells. We hypothesised that loss of PC2 would promote beta cell death and dysfunction in a rodent model of human beta cell proIAPP overexpression...
December 20, 2016: Diabetologia
https://www.readbyqxmd.com/read/27989895/intraperitoneal-injection-of-ido-expressing-dermal-fibroblasts-improves-the-allograft-survival
#13
Mohsen Khosravi-Maharlooei, MohammadReza Pakyari, Reza B Jalili, Ruhangiz T Kilani, Aziz Ghahary
Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme with tolerogenic effects on different immune cells. Our group has previously shown that co-transplantation of IDO-expressing fibroblasts with donor tissues can delay immune rejection by inducing local immunosuppression. In this study, we have employed a systemic approach to improve allograft survival without using any immunosuppressive medication. To achieve this, 10 million lentiviral transduced IDO-expressing donor derived fibroblasts were injected into the peritoneal cavity of allograft recipients...
October 29, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27982034/a-tlr9-agonist-promotes-il-22-dependent-pancreatic-islet-allograft-survival-in-type-1-diabetic-mice
#14
Deepak Tripathi, Sambasivan Venkatasubramanian, Satyanarayana S Cheekatla, Padmaja Paidipally, Elwyn Welch, Amy R Tvinnereim, Ramakrishna Vankayalapati
Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1(+) cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1(+) cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1(+) cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27974246/micrornas-106b-and-222-improve-hyperglycemia-in-a-mouse-model-of-insulin-deficient-diabetes-via-pancreatic-%C3%AE-cell-proliferation
#15
Sohei Tsukita, Tetsuya Yamada, Kei Takahashi, Yuichiro Munakata, Shinichiro Hosaka, Hironobu Takahashi, Junhong Gao, Yuta Shirai, Shinjiro Kodama, Yoichiro Asai, Takashi Sugisawa, Yumiko Chiba, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Hideki Katagiri
Major symptoms of diabetes mellitus manifest, once pancreatic β-cell numbers have become inadequate. Although natural regeneration of β-cells after injury is very limited, bone marrow (BM) transplantation (BMT) promotes their regeneration through undetermined mechanism(s) involving inter-cellular (BM cell-to-β-cell) crosstalk. We found that two microRNAs (miRNAs) contribute to BMT-induced β-cell regeneration. Screening murine miRNAs in serum exosomes after BMT revealed 42 miRNAs to be increased. Two of these miRNAs (miR-106b-5p and miR-222-3p) were shown to be secreted by BM cells and increased in pancreatic islet cells after BMT...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27957767/ethylene-carbodiimide-fixed-donor-splenocytes-combined-with-%C3%AE-1-antitrypsin-induce-indefinite-donor-specific-protection-to-mice-cardiac-allografts
#16
Xingqiang Lai, Longhui Qiu, Yi Zhao, Shuangjin Yu, Chang Wang, Jin Zhang, Fen Ning, Lizhong Chen, Guodong Chen
Peritransplant infusion of ethylene carbodiimide fixed donor splenocytes(ECDI-SPs) induces protection of islet and cardiac allografts. However, pro-inflammatory cytokine production during the peritransplantation period may negate the effect of ECDI-SPs. Therefore, we hypothesized that blocking pro-inflammatory cytokine secretion while increasing levels of anti-inflammatory cytokines would enhance the tolerance-induced efficacy of ECDI-SPs. The objective of this study was to determine the effectiveness of using ECDI-SPs combined with a short course of α1-antitrysin (AAT) for induction of tolerance...
December 13, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27956625/clarifying-intact-3d-tissues-on-a-microfluidic-chip-for-high-throughput-structural-analysis
#17
Yih Yang Chen, Pamuditha N Silva, Abdullah Muhammed Syed, Shrey Sindhwani, Jonathan V Rocheleau, Warren C W Chan
On-chip imaging of intact three-dimensional tissues within microfluidic devices is fundamentally hindered by intratissue optical scattering, which impedes their use as tissue models for high-throughput screening assays. Here, we engineered a microfluidic system that preserves and converts tissues into optically transparent structures in less than 1 d, which is 20× faster than current passive clearing approaches. Accelerated clearing was achieved because the microfluidic system enhanced the exchange of interstitial fluids by 567-fold, which increased the rate of removal of optically scattering lipid molecules from the cross-linked tissue...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27942611/donor-exosomes-rather-than-passenger-leukocytes-initiate-alloreactive-t-cell-responses-after-transplantation
#18
Jose Marino, Mohamed H Babiker-Mohamed, Patrick Crosby-Bertorini, Joshua T Paster, Christian LeGuern, Sharon Germana, Reza Abdi, Mayuko Uehara, James I Kim, James F Markmann, Georges Tocco, Gilles Benichou
Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens. The passenger leukocyte theory states that allograft rejection is initiated by recipient T cells recognizing donor major histocompatibility complex (MHC) molecules displayed on graft leukocytes migrating to the host's lymphoid organs...
July 14, 2016: Science Immunology
https://www.readbyqxmd.com/read/27938490/transgenic-expression-of-glucagon-like-peptide-1-glp-1-and-activated-muscarinic-receptor-m3r-significantly-improves-pig-islet-secretory-function
#19
Nizar Mourad, Andrea Perota, Daela Xhema, Cesare Galli, Pierre Gianello
Porcine islets have notoriously low insulin secretion levels in response to glucose stimulation. While this is somehowexpected in the case of immature islets isolated from fetal and neonatal pigs, disappointingly low secretory responses are frequently reported in studies using <em>in vitro</em>-maturated fetal and neonatal islets and even fully-differentiated adult islets. Herein, we show that beta-cell specific expression of a modified glucagon-like peptide 1 (GLP-1) and of a constitutively activated type 3 muscarinic receptor (M3R) efficiently amplifies glucose-stimulated insulin secretion (GSIS)...
November 22, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27938471/human-recombinant-antithrombin-atrynsup-sup-administration-improves-survival-and-prevents-intravascular-coagulation-after-intraportal-islet-transplantation-in-a-piglet-model
#20
Valery Gmyr, Caroline Bonner, Ericka Moerman, Antoine Tournoys, Nathalie Delalleau, Audrey Quenon, Julien Thevenet, Mikael Chetboun, Julie KerrConte, Franois Pattou, Thomas Hubert, Merce Jourdain
Human islet transplantation is a viable treatment option for type 1 diabetes mellitus (T1D). However, pancreatic isletinflammation after transplantation induced by innate immune responses is likely to hinder graft function. This is mediated by incompatibility between islets and the blood interface, known as instant blood-mediated inflammatory reaction (IBMIR). Herein, we hypothesized that portal venous administration of islet cells with human recombinant antithrombin (ATryn(®)), a serine protease inhibitor (serpin), which plays a central role in the physiological regulation of coagulation and exerts indirect anti-inflammatory activities may offset coagulation abnormalities such as Disseminated Intravascular Coagulation (DIC) and IBMIR...
27, 2016: Cell Transplantation
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