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Islet cell transplantation

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https://www.readbyqxmd.com/read/28324008/vessel-network-architecture-of-adult-human-islets-promotes-distinct-cell-cell-interactions-in-situ-and-is-altered-after-transplantation
#1
Christian M Cohrs, Chunguang Chen, Stephan R Jahn, Julia Stertmann, Helena Chmelova, Jürgen Weitz, Andrea Bähr, Nikolai Klymiuk, Anja Steffen, Barbara Ludwig, Virginia Kamvissi, Eckhard Wolf, Stefan R Bornstein, Michele Solimena, Stephan Speier
Islet cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intra-islet vascularization and paracrine cell signaling are mostly based on rodent pancreas. We here assessed for the first time the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared pancreas tissue slices of fresh tissue obtained from non-diabetic patients undergoing partial pancreatectomy...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322428/xenotransplantation-where-do-we-stand-in-2016
#2
Gisella L Puga Yung, Robert Rieben, Leo Bühler, Henk-Jan Schuurman, Jörg Seebach
Worldwide, there is a constant rise in the number of patients with end-stage organ failure in critical need for transplants, but the number of organs/cells available from deceased or living human donors is limited. Xenotransplantation using pig organs/tissues repre-sents a potential solution for this shortage; however, it has been hampered by a number of mainly immuno-logical hurdles. Remarkable progress was presented at the latest biennial (13th) international congress of the International Xenotransplantation Association, November 2015 in Melbourne, Australia, and the American Transplant Congress, May 2016 in Boston, USA...
March 21, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28321468/hyperglycaemic-memory-affects-the-neurovascular-unit-of-the-retina-in-a-diabetic-mouse-model
#3
Patrick Friedrichs, Andrea Schlotterer, Carsten Sticht, Matthias Kolibabka, Paulus Wohlfart, Axel Dietrich, Thomas Linn, Grietje Molema, Hans-Peter Hammes
AIMS/HYPOTHESIS: The aim of this study was to evaluate damage to the neurovascular unit in a mouse model of hyperglycaemic memory. METHODS: A streptozotocin-induced mouse model of diabetes (C57BL/6J background) received insulin-releasing pellets and pancreatic islet-cell transplantation. Damage to the neurovascular unit was studied by quantitative retinal morphometry for microvascular changes and microarray analysis, with subsequent functional annotation clustering, for changes of the retinal genome...
March 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#4
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28319051/tissue-specific-exosome-biomarkers-for-noninvasively-monitoring-immunologic-rejection-of-transplanted-tissue
#5
Prashanth Vallabhajosyula, Laxminarayana Korutla, Andreas Habertheuer, Ming Yu, Susan Rostami, Chao-Xing Yuan, Sanjana Reddy, Chengyang Liu, Varun Korutla, Brigitte Koeberlein, Jennifer Trofe-Clark, Michael R Rickels, Ali Naji
In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28317340/production-of-pancreatic-progenitor-cells-from-human-induced-pluripotent-stem-cells-using-a-three-dimensional-suspension-bioreactor-system
#6
Yuichiro Mihara, Katsuhisa Matsuura, Yoshihiro Sakamoto, Teruo Okano, Norihiro Kokudo, Tatsuya Shimizu
Islet replacement is a promising strategy for the treatment of patients with type 1 diabetes and patients who have undergone total pancreatectomy. Recent progress in cellular reprogramming technology may allow the transplantation of a patient's own pancreatic cells. Although many studies have reported the differentiation of pancreatic progenitor cells from mouse and human pluripotent stem cells (PSCs), obtaining sufficient cell numbers for clinical applications remains problematic. Here, we describe the mass production of human pancreatic progenitor cells from human induced (i)PSCs using a three-dimensional suspension bioreactor system...
March 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#7
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28293906/who-should-be-considered-for-islet-transplantation-alone
#8
REVIEW
Nantia Othonos, Pratik Choudhary
PURPOSE OF REVIEW: Episodic hypoglycemia is an almost inevitable consequence of exogenous insulin treatment of type 1 diabetes, and in up to 30% of patients, this can lead to impaired awareness of hypoglycemia. This predisposes to recurrent severe hypoglycemia and has a huge impact on quality of life. Although many patients can get resolution of severe hypoglycemia through novel education and technology, some patients continue to have ongoing life-threatening hypoglycemia. Islet transplantation offers an alternative therapeutic option for these patients, in whom these conventional approaches have been unsuccessful...
April 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28290605/transplantation-of-betatrophin-expressing-adipose-derived-mesenchymal-stem-cells-induces-%C3%AE-cell-proliferation-in-diabetic-mice
#9
Liang-Liang Sun, Tian-Jin Liu, Limei Li, Wei Tang, Jun-Jie Zou, Xiang-Fang Chen, Jiao-Yang Zheng, Bei-Ge Jiang, Yong-Quan Shi
Recent progress in regenerative medicine has suggested that mesenchymal stem cell (MSC)-based therapy is a novel potential cure for diabetes. Betatrophin is a newly identified hormone that can increase the production and expansion of insulin-secreting β-cells when administered to mice. In this study, we evaluated the effect of betatrophin overexpression by human adipose-derived MSCs (ADMSCs) by in vitro experiments, as well as following their transplantation into a mice with streptozotocin (STZ)-induced diabetes...
March 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28285194/islet-encapsulation-with-polyphenol-coatings-decreases-pro-inflammatory-chemokine-synthesis-and-t-cell-trafficking
#10
Dana Pham-Hua, Lindsey E Padgett, Bing Xue, Brian Anderson, Michael Zeiger, Jessie M Barra, Maigen Bethea, Chad S Hunter, Veronika Kozlovskaya, Eugenia Kharlampieva, Hubert M Tse
Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to preserve islet function and prevent immune-mediated rejection after transplantation. We previously demonstrated that a novel cytoprotective nanothin multilayer coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), was efficacious in dampening in vitro immune responses involved in transplant rejection and preserving in vitro islet function...
March 6, 2017: Biomaterials
https://www.readbyqxmd.com/read/28280376/single-donor-islet-transplantation-in-type-1-diabetes-patient-selection-and-special-considerations
#11
REVIEW
Jacob A Tatum, Max O Meneveau, Kenneth L Brayman
Type 1 diabetes mellitus is an autoimmune disorder of the endocrine pancreas that currently affects millions of people in the United States. Although the disease can be managed with exogenous insulin administration, the ultimate cure for the condition lies in restoring a patient's ability to produce their own insulin. Islet cell allotransplantation provides a means of endogenous insulin production. Though far from perfected, islet transplants are now a proven treatment for type 1 diabetics. However, proper patient selection is critical for achieving optimal outcomes...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28279194/crispr-targeted-genome-editing-of-mesenchymal-stem-cell-derived-therapies-for-type-1-diabetes-a-path-to-clinical-success
#12
REVIEW
Dario Gerace, Rosetta Martiniello-Wilks, Najah Therese Nassif, Sara Lal, Raymond Steptoe, Ann Margaret Simpson
Due to their ease of isolation, differentiation capabilities, and immunomodulatory properties, the therapeutic potential of mesenchymal stem cells (MSCs) has been assessed in numerous pre-clinical and clinical settings. Currently, whole pancreas or islet transplantation is the only cure for people with type 1 diabetes (T1D) and, due to the autoimmune nature of the disease, MSCs have been utilised either natively or transdifferentiated into insulin-producing cells (IPCs) as an alternative treatment. However, the initial success in pre-clinical animal models has not translated into successful clinical outcomes...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28275376/immunological-balance-is-associated-with-clinical-outcome-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes
#13
Kelen C R Malmegrim, Júlia T C de Azevedo, Lucas C M Arruda, Joana R F Abreu, Carlos E B Couri, Gislane L V de Oliveira, Patricia V B Palma, Gabriela T Scortegagna, Ana B P L Stracieri, Daniela A Moraes, Juliana B E Dias, Fabiano Pieroni, Renato Cunha, Luiza Guilherme, Nathália M Santos, Milton C Foss, Dimas T Covas, Richard K Burt, Belinda P Simões, Júlio C Voltarelli, Bart O Roep, Maria C Oliveira
Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8(+) T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28271465/porcine-islet-xenografts-a-clinical-source-of-%C3%A3-cell-grafts
#14
REVIEW
Bassem F Salama, Gregory S Korbutt
PURPOSE OF REVIEW: Diabetes is medical and social burden affecting millions around the world. Despite intensive therapy, insulin fails to maintain adequate glucose homeostasis and often results in episodes of hypoglycemic unawareness. Islet transplantation is a propitious replacement therapy, and incremental improvements in islet isolation and immunosuppressive drugs have made this procedure a feasible option. Shortage of donors, graft loss, and toxic immunosuppressive agents are few of many hurdles against making human allogenic islet transplantation a routine procedure...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28266044/role-and-impact-of-the-extracellular-matrix-on-integrin-mediated-pancreatic-%C3%AE-cell-functions
#15
REVIEW
Caroline Arous, Bernhard Wehrle-Haller
Understanding the organization and role of the extracellular matrix in islets of Langerhans is critical for maintaining pancreatic β-cells, and to recognize and revert the physiopathology of diabetes. Indeed, integrin-mediated adhesion signaling in response to the pancreatic extracellular matrix plays crucial roles in β-cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic extracellular matrix, their role during integrin-mediated cell-matrix adhesions and how they are affected during diabetes...
March 7, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28263224/acute-ischemia-induced-by-high-density-culture-increases-cytokine-expression-and-diminishes-the-function-and-viability-of-highly-purified-human-islets-of-langerhans
#16
Kate E Smith, Amy C Kelly, Catherine G Min, Craig S Weber, Fiona M McCarthy, Leah V Steyn, Vasudeo Badarinarayana, J Brett Stanton, Jennifer P Kitzmann, Peter Strop, Angelika C Gruessner, Ronald M Lynch, Sean W Limesand, Klearchos K Papas
BACKGROUND: Encapsulation devices have the potential to enable cell based insulin replacement therapies (such as human islet or stem cell derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention...
March 3, 2017: Transplantation
https://www.readbyqxmd.com/read/28260466/leptin-levels-in-patients-with-type-1-diabetes-mellitus-after-fetal-pancreatic-stem-cell-transplant
#17
Olga Ulyanova, Abay Baigenzhin, Zhannat Taubaldieva, Saltanat Tuganbekova, Larissa Kozina, Samat Saparbayev
OBJECTIVES: Our objective was to determine leptin levels in patients with type 1 diabetes mellitus after fetal pancreatic stem cell transplant. MATERIALS AND METHODS: Seven patients, aged 20 to 42 years, with type 1 diabetes mellitus received a fetal pancreatic stem cell transplant by intravenous infusion. The quantity of fetal stem cells infused was ≥ 5 × 10⁶, and the cells were of 12 to 14 weeks of gestation. We analyzed the levels of leptin, C-peptide, and antibodies to the islets of Langerhans before and 3 months after the transplant procedure...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28255157/role-of-high-mobility-group-box-1-hmgb1-in-transplantation-of-rat-pancreatic-islets
#18
Seonghee Jeong, Song Lee, Chan Mee-Lee, In Kyong Shim, Song-Cheol Kim
BACKGROUND The potential role of tissue damage factor high-mobility group box 1 (HMGB1) in islet cell transplantation is poorly understood. We investigated the role of HMGB1 in pancreatic islet cell isolation and culture in vitro and after pancreatic islet cell transplantation into diabetic nude mice in vivo. MATERIAL AND METHODS To generate damaged islets, isolated islets were treated with 1 mg/mL lipopolysaccharide (LPS). Some islets were pretreated with a neutralizing anti-HMGB1 antibody before LPS treatment to investigate the effect of HMGB1 on isolated islets damaged by LPS...
March 3, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28253305/chitosan-assisted-differentiation-of-porcine-adipose-tissue-derived-stem-cells-into-glucose-responsive-insulin-secreting-clusters
#19
Hui-Yu Liu, Chih-Chien Chen, Yuan-Yu Lin, Yu-Jen Chen, Bing-Hsien Liu, Shiu-Chung Wong, Cheng-Yu Wu, Yun-Tsui Chang, Han-Yi E Chou, Shih-Torng Ding
The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates...
2017: PloS One
https://www.readbyqxmd.com/read/28252345/evidence-of-stress-in-%C3%AE-cells-obtained-with-laser-capture-microdissection-from-pancreases-of-brain-dead-donors
#20
Aref Ebrahimi, Min-Ho Jung, Jonathan M Dreyfuss, Hui Pan, Dennis Sgroi, Susan Bonner-Weir, Gordon C Weir
Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolation process, and the complex events that occur during tissue culture. The current study focused upon the events that occur before the islet isolation procedure. Pancreases were obtained from brain dead donors (n = 7) with mean age 50 (11) and normal pancreatic tissue obtained at surgery done for pancreatic neoplasms (n = 7), mean age 69 (9)...
March 4, 2017: Islets
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