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Pancreatic islet transplantation

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https://read.qxmd.com/read/30760930/diabetes-relief-in-mice-by-glucose-sensing-insulin-secreting-human-%C3%AE-cells
#1
Kenichiro Furuyama, Simona Chera, Léon van Gurp, Daniel Oropeza, Luiza Ghila, Nicolas Damond, Heidrun Vethe, Joao A Paulo, Antoinette M Joosten, Thierry Berney, Domenico Bosco, Craig Dorrell, Markus Grompe, Helge Ræder, Bart O Roep, Fabrizio Thorel, Pedro L Herrera
Cell-identity switches, in which terminally differentiated cells are converted into different cell types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic α-cells and somatostatin-producing δ-cells become insulin-expressing cells after the ablation of insulin-secreting β-cells, thus promoting diabetes recovery. Whether human islets also display this plasticity, especially in diabetic conditions, remains unknown...
February 13, 2019: Nature
https://read.qxmd.com/read/30760321/the-role-of-the-vasculature-niche-on-insulin-producing-cells-generated-by-transdifferentiation-of-adult-human-liver-cells
#2
Irit Meivar-Levy, Fatima Zoabi, Gil Nardini, Eugenia Manevitz-Mendelson, Gil S Leichner, Oranit Zadok, Michael Gurevich, Eytan Mor, Simona Dima, Irinel Popescu, Aviv Barzilai, Sarah Ferber, Shoshana Greenberger
BACKGROUND: Insulin-dependent diabetes is a multifactorial disorder that could be theoretically cured by functional pancreatic islets and insulin-producing cell (IPC) implantation. Regenerative medicine approaches include the potential for growing tissues and organs in the laboratory and transplanting them when the body cannot heal itself. However, several obstacles remain to be overcome in order to bring regenerative medicine approach for diabetes closer to its clinical implementation; the cells generated in vitro are typically of heterogenic and immature nature and the site of implantation should be readily vascularized for the implanted cells to survive in vivo...
February 13, 2019: Stem Cell Research & Therapy
https://read.qxmd.com/read/30755634/synergic-effects-of-oxygen-supply-and-antioxidants-on-pancreatic-%C3%AE-cell-spheroids
#3
Dina Myasnikova, Tatsuya Osaki, Kisaki Onishi, Tatsuto Kageyama, Binbin Zhang Molino, Junji Fukuda
Diabetes is one of the most common metabolic disorders, and is characterized by the inability to secrete/sense insulin and abnormal blood glucose concentration. Many researchers have concentrated their efforts on improving islet transplantation, in particular by fabricating bioartificial pancreatic islets in vitro. One of the critical points for the success of this research direction is the improvement of culture conditions, such as oxygen supply, in the engineering of bioartificial pancreatic islets to ensure their viability and functionality after transplantation...
February 12, 2019: Scientific Reports
https://read.qxmd.com/read/30748094/alginate-microencapsulation-of-human-stem-cell-derived-%C3%AE-cells-with-cxcl12-prolongs-their-survival-and-function-in-immunocompetent-mice-without-systemic-immunosuppression
#4
David A Alagpulinsa, Jenny J L Cao, Riley K Driscoll, Ruxandra F Sîrbulescu, Madeline F E Penson, Marinko Sremac, Elise N Engquist, Timothy A Brauns, James F Markmann, Douglas A Melton, Mark C Poznansky
Pancreatic β-cell replacement by islet transplantation for the treatment of Type 1 Diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells, so-called SC-β cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to β-cell replacement. Nonetheless, inflammatory foreign body responses leading to pericapsular fibrotic overgrowth often causes microencapsulated islet-cell death and graft failure...
February 12, 2019: American Journal of Transplantation
https://read.qxmd.com/read/30742984/type-1-diabetes-mellitus-reversal-via-implantation-of-magnetically-purified-microencapsulated-pseudoislets
#5
A Espona-Noguera
Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host's immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device...
February 8, 2019: International Journal of Pharmaceutics
https://read.qxmd.com/read/30738185/paving-the-way-for-successful-islet-encapsulation
#6
REVIEW
Nikos Dimitrioglou, Maria Kanelli, Efstathia Papageorgiou, Theodore Karatzas, Dimitris Hatziavramidis
Type 1 diabetes mellitus (T1DM) is a disorder that decimates pancreatic β-cells which produce insulin. Direct pancreatic islet transplantation cannot serve as a widespread therapeutic modality owing to the need for lifelong immunosuppression and donor shortage. Therefore, several encapsulation techniques have been developed to enclose the islets in semipermeable vehicles that will allow oxygen and nutrient input as well as insulin, other metabolites and waste output, while accomplishing immunoisolation. Although encapsulation technology continues to face significant obstacles, recent advances in material science, stem cell biology and immunology potentially serve as pathways to success...
February 6, 2019: Drug Discovery Today
https://read.qxmd.com/read/30719867/concise-review-canine-diabetes-mellitus-as-a-translational-model-for-innovative-regenerative-medicine-approaches
#7
REVIEW
Maryam Moshref, Bonnie Tangey, Chen Gilor, Klearchos K Papas, Peter Williamson, Lindsey Loomba-Albrecht, Paul Sheehy, Amir Kol
Diabetes mellitus (DM) is a common spontaneous endocrine disorder in dogs, which is defined by persistent hyperglycemia and insulin deficiency. Like type 1 diabetes (T1D) in people, canine DM is a complex and multifactorial disease in which genomic and epigenomic factors interact with environmental cues to induce pancreatic β-cell loss and insulin deficiency, although the pathogenesis of canine DM is poorly defined and the role of autoimmunity is further controversial. Both diseases are incurable and require life-long exogenous insulin therapy to maintain glucose homeostasis...
February 5, 2019: Stem Cells Translational Medicine
https://read.qxmd.com/read/30710150/recapitulating-endocrine-cell-clustering-in-culture-promotes-maturation-of-human-stem-cell-derived-%C3%AE-cells
#8
Gopika G Nair, Jennifer S Liu, Holger A Russ, Stella Tran, Michael S Saxton, Richard Chen, Charity Juang, Mei-Lan Li, Vinh Q Nguyen, Simone Giacometti, Sapna Puri, Yuan Xing, Yong Wang, Gregory L Szot, Jose Oberholzer, Anil Bhushan, Matthias Hebrok
Despite advances in the differentiation of insulin-producing cells from human embryonic stem cells, the generation of mature functional β cells in vitro has remained elusive. To accomplish this goal, we have developed cell culture conditions to closely mimic events occurring during pancreatic islet organogenesis and β cell maturation. In particular, we have focused on recapitulating endocrine cell clustering by isolating and reaggregating immature β-like cells to form islet-sized enriched β-clusters (eBCs)...
February 2019: Nature Cell Biology
https://read.qxmd.com/read/30709732/radiological-advances-in-pancreatic-islet-transplantation
#9
REVIEW
Donal Cahill, Fernanda Zamboni, Maurice N Collins
Type 1 diabetes mellitus (T1DM) is characterized by hyperglycemia, owing to the loss of pancreatic β cells in response to an autoimmune reaction leading to a state of absolute insulin deficiency. T1DM treatment is shifting from exogenous insulin replacement therapy toward pancreatic β-cell replacement, to restore physiologically responsive insulin secretion to variations in blood glucose levels. β-cell replacement strategies include human whole pancreas transplantation, islet transplantation with cell encapsulation and bioengineered pancreas...
January 29, 2019: Academic Radiology
https://read.qxmd.com/read/30701283/operational-immune-tolerance-towards-transplanted-allogeneic-pancreatic-islets-in-mice-and-a-non-human-primate
#10
Midhat H Abdulreda, Dora M Berman, Alexander Shishido, Christopher Martin, Maged Hossameldin, Ashley Tschiggfrie, Luis F Hernandez, Ana Hernandez, Camillo Ricordi, Jean-Marie Parel, Ewa Jankowska-Gan, William J Burlingham, Esdras A Arrieta-Quintero, Victor L Perez, Norma S Kenyon, Per-Olof Berggren
AIMS/HYPOTHESIS: Patients with autoimmune type 1 diabetes transplanted with pancreatic islets to their liver experience significant improvement in quality of life through better control of blood sugar and enhanced awareness of hypoglycaemia. However, long-term survival and efficacy of the intrahepatic islet transplant are limited owing to liver-specific complications, such as immediate blood-mediated immune reaction, hypoxia, a highly enzymatic and inflammatory environment and locally elevated levels of drugs including immunosuppressive agents, all of which are injurious to islets...
January 31, 2019: Diabetologia
https://read.qxmd.com/read/30699366/heat-shock-protein-b1-is-a-key-mediator-of-prolactin-induced-beta-cell-cytoprotection-against-oxidative-stress
#11
Letícia F Terra, Rosangela A M Wailemann, Ancély F Dos Santos, Vinicius M Gomes, Railmara P Silva, Anna Laporte, Flávia C Meotti, Walter R Terra, Giuseppe Palmisano, Stephan Lortz, Leticia Labriola
Maintaining islet cell viability in vitro, although challenging, appears to be a strategy for improving the outcome of pancreatic islet transplantation. We have shown that prolactin (PRL) leads to beta-cell cytoprotection against apoptosis, an effect mediated by heat shock protein B1 (HSPB1). Since the role of HSPB1 in beta-cells is still unclear and the hormone concentration used is not compatible with clinical applications because of all the side effects displayed by the hormone in other tissues, we explored the molecular mechanisms by which HSPB1 mediates beta-cell cytoprotection...
January 27, 2019: Free Radical Biology & Medicine
https://read.qxmd.com/read/30697608/current-state-and-future-evolution-of-pancreatic-islet-transplantation
#12
REVIEW
Takayuki Anazawa, Hideaki Okajima, Toshihiko Masui, Shinji Uemoto
Pancreatic islet transplantation provides an effective treatment option for patients with type 1 diabetes (T1D) with intractable impaired awareness of hypoglycemia and severe hypoglycemic events. Currently, the primary goal of islet transplantation should be excellent glycemic control without severe hypoglycemia, rather than insulin independence. Islet transplant recipients were less likely to achieve insulin independence, whereas solid pancreas transplant recipients substantially had greater procedure-related morbidity...
January 2019: Annals of gastroenterological surgery
https://read.qxmd.com/read/30688734/baseline-pancreatic-beta-cell-imaging-after-pancreatic-transplantation-using-whole-body-68ga-dota-exendin-4-pet-ct-a-spectrum-of-2-cases-of-diabetes-mellitus
#13
Aashish Gambhir, Avani Jain, Indirani Elangovan, Shelley Simon
Whole pancreatic transplant and islet cells transplantation are currently available strategies aiming toward diabetes cure. Beta cell specific noninvasive functional imaging using novel PET radiotracers are now available and can be used for beta cell imaging and quantification. Herein we describe a spectrum of 2 cases demonstrating beta cell targeted imaging using Ga-DOTA-exendin-4 PET/CT in patients with diabetes after simultaneous pancreas-kidney transplantation.
January 25, 2019: Clinical Nuclear Medicine
https://read.qxmd.com/read/30680957/mesenchymal-stem-cells-from-chronic-pancreatitis-patients-show-comparable-potency-compared-to-cells-from-healthy-donors
#14
Jingjing Wang, Yong Zhang, Colleen Cloud, Tara Duke, Stefanie Owczarski, Shikhar Mehrotra, David B Adams, Katherine Morgan, Gary Gilkeson, Hongjun Wang
Mesenchymal stem cells (MSCs) are proven to be beneficial in islet transplantation, suggesting a potential therapeutic role of them in total pancreatectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) patients. We investigated whether MSCs derived from CP patients are suitable for use in autologous cell therapy. MSCs from healthy donors (H-MSCs) and CP patients (CP-MSCs) were studied for phenotype, colony formation potential, multilineage differentiation ability, proliferation, senescence, secretory characters, and immunosuppressive functions...
January 24, 2019: Stem Cells Translational Medicine
https://read.qxmd.com/read/30678946/pancreatic-stem-cells-differentiate-into-insulin-secreting-cells-on-fibroblast-modified-plga-membranes
#15
Jing Tan, Liping Liu, Baoyuan Li, Qian Xie, Junwen Sun, Hongli Pu, Li Zhang
Diabetes mellitus is an epidemic worldwide. Pancreatic stem cells can be induced to differentiate into insulin-secreting cells, this method is an effective way to solve the shortage of islet donor. Poly (lactic acid-co-glycolic acid (PLGA) copolymer is an excellent scaffold for tissue engineering as it presents good biocompatibility and film forming properties. In this study, we adopted biological methods, using fibroblast-coated PLGA diaphragm to form a biological membrane, and then pancreatic stem cells were cultured on the fibroblast-modified PLGA membrane and the two-step induction method was utilized to induce the differentiation of pancreatic stem cells into insulin-secreting cells...
April 2019: Materials Science & Engineering. C, Materials for Biological Applications
https://read.qxmd.com/read/30677477/the-eye-as-a-novel-imaging-site-in-diabetes-research
#16
REVIEW
Shao-Nian Yang, Per-Olof Berggren
Diabetes develops due to deficient functional β cell mass, insulin resistance, or both. Yet, various challenges in understanding the mechanisms underlying diabetes development in vivo remain to be overcome owing to the lack of appropriate intravital imaging technologies. To meet these challenges, we have exploited the anterior chamber of the eye (ACE) as a novel imaging site to understand diabetes basics and clinics in vivo. We have developed a technology platform transplanting pancreatic islets into the ACE where they later on can be imaged non-invasively for long time...
January 21, 2019: Pharmacology & Therapeutics
https://read.qxmd.com/read/30674070/human-multipotent-stromal-cell-secreted-effectors-accelerate-islet-regeneration
#17
Miljan Kuljanin, Ruth M Elgamal, Gillian I Bell, Anargyros Xenocostas, Gilles A Lajoie, David A Hess
Human multipotent stromal cells (hMSC) can induce islet regeneration after transplantation via the secretion of proteins that establish an islet regenerative niche. However, the identity of hMSC-secreted signals and the mechanisms by which pancreatic islet regeneration is induced remain unknown. Recently, mammalian pancreatic α-cells have been shown to possess considerable plasticity, and differentiate into β-like cells after near complete β-cell loss or overexpression of key transcriptional regulators. These studies have generated new excitement that islet regeneration during diabetes may be possible if we can identify clinically applicable stimuli to modulate these key regulatory pathways...
January 23, 2019: Stem Cells
https://read.qxmd.com/read/30670068/adipocyte-derived-stem-cell-based-gene-therapy-upon-adipogenic-differentiation-on-microcarriers-attenuates-type-1-diabetes-in-mice
#18
Qing Fang, Min Zhai, Shan Wu, Xiaogen Hu, Zhan Hua, Huizhuo Sun, Jing Guo, Wenjian Zhang, Zai Wang
BACKGROUND: Insulin replenishment is critical for patients with type 1 diabetes; however, current treatments such as pancreatic islet transplantation and insulin injection are not ideal. In addition to stem cell or gene therapy alone, stem cell combined with gene therapy may provide a new route for insulin replenishment, which could avoid an autoimmune reaction against differentiated β cells or systematic viral vector injection. METHODS: In this study, human adipocyte-derived stem cells (ADSCs) were transducted with lentiviral vectors expressing a furin-cleavable insulin gene...
January 22, 2019: Stem Cell Research & Therapy
https://read.qxmd.com/read/30662261/in-situ-graphene-liquid-cell-transmission-electron-microscopy-study-of-insulin-secretion-in-pancreatic-islet-cells
#19
Emre Firlar, Meagan Ouy, Leigha Covnot, Yuan Xing, Daniel Lee, Alessandro Chan, Yi He, Boao Song, Solomon Afelik, Yong Wang, Reza Shahbazian-Yassar, Jose Oberholzer, Tolou Shokuhfar
Background: Islet cell transplantation is one of the key treatments for type 1 diabetes. Understanding the mechanisms of insulin fusion and exocytosis are of utmost importance for the improvement of the current islet cell transplantation and treatment of diabetes. These phenomena have not been fully evaluated due either to the lack of proper dynamic imaging, or the lack of proper cell preservation during imaging at nanoscales. Methods: By maintaining the native environment of pancreatic β-cells between two graphene monolayer sheets, we were able to monitor the subcellular events using in situ graphene liquid cell (GLC)-transmission electron microscopy (TEM) with both high temporal and high spatial resolution...
2019: International Journal of Nanomedicine
https://read.qxmd.com/read/30661993/acquisition-of-dynamic-function-in-human-stem-cell-derived-%C3%AE-cells
#20
Leonardo Velazco-Cruz, Jiwon Song, Kristina G Maxwell, Madeleine M Goedegebuure, Punn Augsornworawat, Nathaniel J Hogrebe, Jeffrey R Millman
Recent advances in human pluripotent stem cell (hPSC) differentiation protocols have generated insulin-producing cells resembling pancreatic β cells. While these stem cell-derived β (SC-β) cells are capable of undergoing glucose-stimulated insulin secretion (GSIS), insulin secretion per cell remains low compared with islets and cells lack dynamic insulin release. Herein, we report a differentiation strategy focused on modulating transforming growth factor β (TGF-β) signaling, controlling cellular cluster size, and using an enriched serum-free media to generate SC-β cells that express β cell markers and undergo GSIS with first- and second-phase dynamic insulin secretion...
December 31, 2018: Stem Cell Reports
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