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Islet cell transplantation

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https://www.readbyqxmd.com/read/29453879/defining-outcomes-for-%C3%AE-cell-replacement-therapy-in-the-treatment-of-diabetes-a-consensus-report-on-the-igls-criteria-from-the-ipita-epita-opinion-leaders-workshop
#1
REVIEW
Michael R Rickels, Peter G Stock, Eelco J P de Koning, Lorenzo Piemonti, Johann Pratschke, Rodolfo Alejandro, Melena D Bellin, Thierry Berney, Pratik Choudhary, Paul R Johnson, Raja Kandaswamy, Thomas W H Kay, Bart Keymeulen, Yogish C Kudva, Esther Latres, Robert M Langer, Roger Lehmann, Barbara Ludwig, James F Markmann, Marjana Marinac, Jon S Odorico, François Pattou, Peter A Senior, James A M Shaw, Marie-Christine Vantyghem, Steven White
β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia...
February 17, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29452233/role-of-adipose-tissue-derived-stem-cells-differentiated-into-insulin-producing-cells-in-the-treatment-of-type-i-diabetes-mellitus
#2
Mona G Amer, Azza S Embaby, Rehab A Karam, Marwa G Amer
Generation of new β cells is an important approach in the treatment of type 1 diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be one of the best sources for cell replacement therapy for diabetes. Therefore, this work aimed to test the possible role of transplanted insulin-producing cells (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced type I DM in rats. Type 1 DM was induced by single intra peritoneal injection with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and the other half were injected with differentiated IPCs directly into the pancreas...
February 13, 2018: Gene
https://www.readbyqxmd.com/read/29433332/generation-of-high-yield-insulin-producing-cells-from-human-induced-pluripotent-stem-cells-on-polyethersulfone-nanofibrous-scaffold
#3
Reyhaneh Nassiri Mansour, Ghasem Barati, Masoud Soleimani, Pegah Ghoraeian, Maryam Nouri Aleagha, Mousa Kehtari, Hossein Mahboudi, Fatemeh Hosseini, Hadi Hassannia, Mohammad Foad Abazari, Seyed Ehsan Enderami
Transplantation of islet is a promising method in treatment of patients with type 1 diabetes mellitus (T1DM), however, is limited by islet shortage. The aim of this study was to prepare a polyethersulfone (PES) nanofibrous scaffolds to evaluate the pancreatic differentiation of human induced pluripotent stem cells (hiPSCs). The differentiation process in tissue culture dishes and PES scaffolds was evaluated at mRNA and protein level by RT-qPCR and immunofluorescence assay, respectively. The functionality of differentiated cells was determined by insulin and C-peptide release in response to glucose challenges...
February 12, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29431690/ildr2-fc-is-a-novel-regulator-of-immune-homeostasis-and-inducer-of-antigen-specific-immune-tolerance
#4
Joseph R Podojil, Iris Hecht, Ming-Yi Chiang, Ilan Vaknin, Inbal Barbiro, Amit Novik, Eyal Neria, Galit Rotman, Stephen D Miller
ILDR2 is a member of the Ig superfamily, which is implicated in tricellular tight junctions, and has a putative role in pancreatic islet health and survival. We recently found a novel role for ILDR2 in delivering inhibitory signals to T cells. In this article, we show that short-term treatment with ILDR2-Fc results in long-term durable beneficial effects in the relapsing-remitting experimental autoimmune encephalomyelitis and NOD type 1 diabetes models. ILDR2-Fc also promotes transplant engraftment in a minor mismatch bone marrow transplantation model...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29428804/links-between-a-biomarker-profile-cold-ischaemic-time-and-clinical-outcome-following-simultaneous-pancreas-and-kidney-transplantation
#5
Hussein A Khambalia, M Yvonne Alexander, Mahesan Nirmalan, Ria Weston, Phillip Pemberton, Zia Moinuddin, Angela Summers, David van Dellen, Titus Augustine
In sepsis, trauma and major surgery, where an explicit physiological insult leads to a significant systemic inflammatory response, the acute evolution of biomarkers have been delineated. In these settings, Interleukin (IL) -6 and TNF-α are often the first pro-inflammatory markers to rise, stimulating production of acute phase proteins followed by peaks in anti-inflammatory markers. Patients undergoing SPKT as a result of diabetic complications already have an inflammatory phenotype as a result of uraemia and glycaemia...
February 8, 2018: Cytokine
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...
February 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29415820/differentially-methylated-circulating-dna-a-novel-biomarker-to-monitor-beta-cell-death
#7
REVIEW
Yingfeng Liu, Qiyuan Tan, Fang Liu
Diabetes mellitus (DM) is a metabolic disorder of glucose homeostasis caused by insufficient secretion or inadequate action of insulin. Nowadays, the increased morbidity of DM is a worldwide issue. Pancreatic beta cell death plays a key role in the progress of DM, especially Type 1 diabetes (T1D). Traditional biomarkers, such as C-peptide and islet autoimmune antibodies are limited to reflect beta cell death and to identify high risk patients in the clinical practice. Recently, a novel biomarker, differentially methylated circulating DNA, has become a research hotspot...
September 1, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29407342/layer-by-layer-cell-coating-technique-using-extracellular-matrix-facilitates-rapid-fabrication-and-function-of-pancreatic-%C3%AE-cell-spheroids
#8
Yasunari Fukuda, Takami Akagi, Tadafumi Asaoka, Hidetoshi Eguchi, Kazuki Sasaki, Yoshifumi Iwagami, Daisaku Yamada, Takehiro Noda, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Masaki Mori, Yuichiro Doki, Mitsuru Akashi
Tissue engineering of insulin-secreting cells using alternatives to islet transplantation has been fueled by the development of available materials and fabrication techniques. We have established a cell coating technique that enables the cell surface to be coated with extracellular matrix based on the concept of a layer-by-layer (LbL) assembly. The present study evaluated whether this technique is beneficial for fabricating pancreatic β-cell spheroids using a mouse β-cell line. The well-structured and dense spheroids could immediately be constructed by the LbL-coated cells...
January 16, 2018: Biomaterials
https://www.readbyqxmd.com/read/29401607/mscs-promote-the-development-and-improve-the-function-of-neonatal-porcine-islet-grafts
#9
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/29395812/the-prognostic-significance-of-glutamic-acid-decarboxylase-antibodies-in-patients-with-chronic-pancreatitis-undergoing-total-pancreatectomy-with-islet-autotransplantation
#10
M Kizilgul, J J Wilhelm, T B Dunn, G J Beilman, T L Pruett, S Chinnakotla, K Amin, B J Hering, M D Bellin
AIM: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT...
January 11, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29394145/the-journey-of-islet-cell-transplantation-and-future-development
#11
Anissa Gamble, Andrew R Pepper, Antonio Bruni, A M James Shapiro
Intraportal islet transplantation has proven to be efficacious in preventing severe hypoglycemia and restoring insulin independence in selected patients with type 1 diabetes. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet cell loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction, potent host auto- and alloimmune responses, and beta cell toxicity from immunosuppressive agents...
February 2, 2018: Islets
https://www.readbyqxmd.com/read/29382312/stem-cells-and-beta-cell-replacement-therapy-a-prospective-health-technology-assessment-study
#12
Klemens Wallner, Rene G Pedroza, Isaac Awotwe, James M Piret, Peter A Senior, A M James Shapiro, Christopher McCabe
BACKGROUND: Although current beta cell replacement therapy is effective in stabilizing glycemic control in highly selected patients with refractory type 1 diabetes, many hurdles are inherent to this and other donor-based transplantation methods. One solution could be moving to stem cell-derived transplant tissue. This study investigates a novel stem cell-derived graft and implant technology and explores the circumstances of its cost-effectiveness compared to intensive insulin therapy...
January 30, 2018: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/29378867/iapp-and-type-1-diabetes-implications-for-immunity-metabolism-and-islet-transplants
#13
REVIEW
Heather C Denroche, C Bruce Verchere
Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP have not been implicated in type 1 diabetes, they are potent pro-inflammatory stimuli to innate immune cells, and thus, could influence autoimmunity...
February 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29372538/sustained-exenatide-delivery-via-intracapsular-microspheres-for-improved-survival-and-function-of-microencapsulated-porcine-islets
#14
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/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#15
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29333922/effect-of-resveratrol-treatment-on-graft-revascularization-after-islet-transplantation-in-streptozotocin-induced-diabetic-mice
#16
Eun-Mi Lee, Inwon Park, Ye-Jee Lee, Young-Hye You, Ji-Won Kim, Myung-Jun Kim, Yu-Bae Ahn, Pilhan Kim, Seung-Hyun Ko
We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O2 1%, 1hr)...
January 15, 2018: Islets
https://www.readbyqxmd.com/read/29331269/clinical-benefits-of-autologous-haematopoietic-stem-cell-transplantation-in-type-1-diabetes-patients
#17
B Gu, H Miao, J Zhang, J Hu, W Zhou, W Gu, W Wang, G Ning
Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet function through immunological attack; therefore, it is also called 'insulin-dependent diabetes'. The present study aimed to evaluate the safety and clinical efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel-assignment, non-randomized trial was conducted from March 2008 to December 2011 with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only with insulin injections...
December 22, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29330944/improvement-of-islet-function-and-survival-by-integration-of-perfluorodecalin-into-microcapsules-in-vivo-and-in-vitro
#18
Sang-Ho Lee, Heon-Seok Park, Yeoree Yang, Eun-Young Lee, Ji-Won Kim, Gilson Khang, Kun-Ho Yoon
Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained...
January 12, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29330151/interleukin-22-reverses-human-islet-dysfunction-and-apoptosis-triggered-by-hyperglycemia-and-light
#19
Shadab Abadpour, Bente Halvorsen, Afaf Sahraoui, Olle Korsgren, Pål Aukrust, Hanne Scholz
Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22...
January 12, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29329189/beta-cell-death-by-cell-free-dna-and-outcome-after-clinical-islet-transplantation
#20
Boris L Gala-Lopez, Daniel Neiman, Tatsuya Kin, Doug O'Gorman, Andrew R Pepper, Andrew J Malcolm, Sheina Pianzin, Peter A Senior, Patricia Campbell, Benjamin Glaser, Yuval Dor, Ruth Shemer, A M James Shapiro
BACKGROUND: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss, and was recently validated in new-onset type 1 diabetes and in islet transplant patients. METHODS: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes...
January 11, 2018: Transplantation
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