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https://www.readbyqxmd.com/read/28885496/%C3%A3-cell-replacement-therapy-the-next-10-years
#1
Christian Schuetz, Takayuki Anazawa, Sarah E Cross, Leticia Labriola, Raphael P H Meier, Robert R Redfield, Hanne Scholz, Peter G Stock, Nathan W Zammit
ß cell replacement with either pancreas or islet transplantation has progressed immensely over the last decades with current 1- and 5-year insulin independence rates of ~85% and ~50%, respectively. Recent advances are largely attributed to improvements in immunosuppressive regimen, donor selection and surgical technique. However, both strategies are compromised by a scarce donor source. Xenotransplantation provides a potential solution by providing a theoretically unlimited supply of islets, but clinical application has been limited by concerns for a potent immune response against xenogeneic tissue...
September 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28870071/an-orcein-related-small-molecule-o4-destabilizes-hiapp-protofibrils-by-interacting-mostly-with-the-amyloidogenic-core-region
#2
Yu Zou, Zhenyu Qian, Yunxiang Sun, Guanghong Wei, Qingwen Zhang
The accumulation of the human islet amyloid polypeptide (hIAPP) deposits in the pancreas is regarded as an important factor that leads to the depletion of islet β-cells and islet transplantation failure. Recent experiments reported that small organic molecule O4 inhibits the formation of hIAPP1-37 oligomers and fibrils. However, the interaction between O4 molecules and hIAPP oligomers is largely unknown at atomic level. In this work, we studied the influence of O4 molecules on fibril-like hIAPP pentamer and decamer by performing atomistic molecular dynamics simulations...
September 4, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28854965/adipose-stem-cells-from-chronic-pancreatitis-patients-improve-mouse-and-human-islet-survival-and-function
#3
Lili Song, Zhen Sun, Do-Sung Kim, Wenyu Gou, Charlie Strange, Huansheng Dong, Wanxing Cui, Gary Gilkeson, Katherine A Morgan, David B Adams, Hongjun Wang
BACKGROUND: Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation...
August 30, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28843156/small-molecule-at7867-proliferates-pdx1-expressing-pancreatic-progenitor-cells-derived-from-human-pluripotent-stem-cells
#4
Azuma Kimura, Taro Toyoda, Yohei Nishi, Makoto Nasu, Akira Ohta, Kenji Osafune
While pancreatic islet transplantation achieves insulin independence in type 1 diabetes (T1D) patients, its widespread application is limited by donor tissue scarcity. Pancreatic progenitor cells (PPCs) give rise to all cell types in the pancreas during development. PPCs derived from human pluripotent stem cells have been shown to differentiate into functional β cells both in vitro and in vivo, and to reverse hyperglycemia, at least in mice. Therefore, PPCs have great potential to serve as an alternative cell source for cell therapy, and the identification of compounds that facilitate PPC proliferation could provide stable and large-scale pancreatic cell preparation systems in clinical settings...
August 17, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28835662/pancreatic-islet-macroencapsulation-using-microwell-porous-membranes
#5
Katarzyna Skrzypek, Milou Groot Nibbelink, Jéré van Lente, Mijke Buitinga, Marten A Engelse, Eelco J P de Koning, Marcel Karperien, Aart van Apeldoorn, Dimitrios Stamatialis
Allogeneic islet transplantation into the liver in combination with immune suppressive drug therapy is widely regarded as a potential cure for type 1 diabetes. However, the intrahepatic system is suboptimal as the concentration of drugs and nutrients there is higher compared to pancreas, which negatively affects islet function. Islet encapsulation within semipermeable membranes is a promising strategy that allows for the islet transplantation outside the suboptimal liver portal system and provides environment, where islets can perform their endocrine function...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835141/transplantation-of-stromal-derived-factor-1%C3%AE-and-basic-fibroblast-growth-factor-primed-insulin-producing-cells-reverses-hyperglycaemia-in-diabetic-rats
#6
Muhammad Sohail Anjum, Azra Mehmood, Muhammad Ali, Hira Butt, Shaheen N Khan, Sheikh Riazuddin
The defective insulin production is associated with severely reduced islet cell mass leading to diabetes. Growth factors preconditioned stem cells have arisen as an effective therapy to treat many diseases including diabetes. The current study was designed to assess the effect of pretreatment of ASCs derived IPCs with combination of stromal cell derived factor 1 alpha (SDF1α) and basic fibroblast growth factor (bFGF) in improving glucose tolerance in streptozotocin induced diabetic rats. The results showed maximally significant reduction in hyperglycaemia and fibrosis, while up-regulation of survival and pancreas-specific genes, insulin levels and homing of transplanted cells in SDF-1α + bFGF IPCs transplanted rats as compared with other groups...
August 24, 2017: Growth Factors
https://www.readbyqxmd.com/read/28832685/oxygen-environment-and-islet-size-are-the-primary-limiting-factors-of-isolated-pancreatic-islet-survival
#7
Hirotake Komatsu, Colin Cook, Chia-Hao Wang, Leonard Medrano, Henry Lin, Fouad Kandeel, Yu-Chong Tai, Yoko Mullen
BACKGROUND: Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency. METHODOLOGY: The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model...
2017: PloS One
https://www.readbyqxmd.com/read/28830425/improved-yield-of-canine-islet-isolation-from-deceased-donors
#8
Stephen Harrington, S Janette Williams, Vern Otte, Sally Barchman, Cheryl Jones, Karthik Ramachandran, Lisa Stehno-Bittel
BACKGROUND: Canine diabetes is a strikingly prevalent and growing disease, and yet the standard treatment of a twice-daily insulin injection is both cumbersome to pet owners and only moderately effective. Islet transplantation has been performed with repeated success in canine research models, but has unfortunately not been made available to companion animals. Standard protocols for islet isolation, developed primarily for human islet transplantation, include beating-heart organ donation, vascular perfusion of preservation solutions, specialized equipment...
August 22, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28793270/pancreatic-islet-blood-flow-dynamics-in-primates
#9
Juan A Diez, Rafael Arrojo E Drigo, Xiaofeng Zheng, Olga V Stelmashenko, Minni Chua, Rayner Rodriguez-Diaz, Masahiro Fukuda, Martin Köhler, Ingo Leibiger, Sai Bo Bo Tun, Yusuf Ali, George J Augustine, Veluchamy A Barathi, Per-Olof Berggren
Blood flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the pancreas. Blood flow velocity in the engrafted islets was not affected by increasing blood glucose levels and/or the GLP-1R agonist liraglutide...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28751653/biochemical-profiling-of-diabetes-disease-progression-by-multivariate-vibrational-microspectroscopy-of-the-pancreas
#10
Christoffer Nord, Maria Eriksson, Andrea Dicker, Anna Eriksson, Eivind Grong, Erwin Ilegems, Ronald Mårvik, Bård Kulseng, Per-Olof Berggren, András Gorzsás, Ulf Ahlgren
Despite the dramatic increase in the prevalence of diabetes, techniques for in situ studies of the underlying pancreatic biochemistry are lacking. Such methods would facilitate obtaining mechanistic understanding of diabetes pathophysiology and aid in prognostic and/or diagnostic assessments. In this report we demonstrate how a multivariate imaging approach (orthogonal projections to latent structures - discriminant analysis) can be applied to generate full vibrational microspectroscopic profiles of pancreatic tissues...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28731996/-pancreatitis-genes-and-islet-cells-auto-transplant-updates-and-new-horizons
#11
Edgardo D Rivera Rivera
Pancreatitis is an inflammation of the pancreas that can progress from an acute presentation to an acute recurring presentation and eventually to chronic pancreatitis, which is characterized by irreversible morphological changes and scarring of the pancreas. The entity known as hereditary pancreatitis has been recognized in the literature for years and certainly the discovery of the PRSS1 gene in 1996 marked the beginning of a new era of genetic discoveries associated with the disease. Since then, multiple genes have been described as the causing agents of pancreatitis or disease modifiers, some of the most important ones being the PRSS1, SPINK1, CFTR, CASR, CTRC, CLDN2, and CPA1...
April 2017: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/28726153/immunological-issues-after-stem-cell-based-%C3%AE-cell-replacement
#12
REVIEW
Valeria Sordi, Silvia Pellegrini, Lorenzo Piemonti
PURPOSE OF REVIEW: Islet and pancreas transplantation prove that β cell replacement can cure the glycemic derangements in type 1 diabetes (T1D). Induced pluripotent stem cells (iPSCs) can differentiate into functional insulin-producing cells, able to restore normoglycemia in diabetic animal models. iPSCs in particular can be derived from the somatic cells of a person with T1D. This review aims to clarify if it is possible to transplant autologous iPSC-derived β cells without immunosuppression or which are the alternative approaches...
September 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28685509/stepwise-approach-to-problematic-hypoglycemia-in-korea-educational-technological-and-transplant-interventions
#13
REVIEW
Sang Man Jin
Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring...
June 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28655312/transplantation-of-human-fetal-pancreatic-progenitor-cells-ameliorates-renal-injury-in-streptozotocin-induced-diabetic-nephropathy
#14
Yongwei Jiang, Wenjian Zhang, Shiqing Xu, Hua Lin, Weiguo Sui, Honglin Liu, Liang Peng, Qing Fang, Li Chen, Jinning Lou
BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem. OBJECTIVE: To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM...
June 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28639386/development-of-immune-response-to-tissue-restricted-self-antigens-in-simultaneous-kidney-pancreas-transplant-recipients-with-acute-rejection
#15
Muthukumar Gunasekaran, Neeta Vachharajani, Joseph P Gaut, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, William C Chapman, Jason Wellen, Thalachallour Mohanakumar
Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#16
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632818/benefits-of-islet-transplantation-as-an-alternative-to-pancreas-transplantation-retrospective-study-of-more-than-10-ten-years-of-experience-in-a-single-center
#17
Barbora Voglová, Martina Zahradnická, Peter Girman, Jan Kríž, Zuzana Berková, Tomáš Koblas, Ema Vávrová, Lenka Németová, Lucie Kosinová, David Habart, Eva Fábryová, Eva Dovolilová, Ivan Leontovyc, Tomáš Neškudla, Jan Peregrin, Jozef Kovác, Kvetoslav Lipár, Matej Kocík, Tomáš Marada, Jirí Svoboda, František Saudek
BACKGROUND: Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. AIM: This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28583545/simultaneous-subtotal-pancreatectomy-and-streptozotocin-injection-for-diabetes-modeling-in-cynomolgus-monkeys
#18
H Park, J B Park, J H Kim, K W Lee, H S Lee, G-S Kim, D-Y Shin, S-H Oh, S-M Jin, S J Kim
BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28583543/laparoscopy-assisted-spleen-preserving-distal-pancreatectomy-for-living-donor-pancreas-transplantation
#19
S Date, H Noguchi, K Kaku, K Kurihara, Y Miyasaka, Y Okabe, U Nakamura, T Ohtsuka, M Nakamura
BACKGROUND: Living pancreas transplantation plays an important role in the treatment of patients with severe type 1 diabetes. However, pancreatectomy is very invasive for the donor, and less-invasive surgical procedures are needed. Although some reports have described hand-assisted laparoscopic surgery for distal pancreatectomy in living-donor operations, less-invasive laparoscopy-assisted (LA) procedures are expected to increase the donor pool. We herein report the outcomes of four cases of LA spleen-preserving distal pancreatectomy (Warshaw technique [WT]) in living pancreas donors...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28562418/autologous-islet-transplantation-challenges-and-lessons
#20
Ty B Dunn, Joshua J Wilhelm, Melena D Bellin, Timothy L Pruett
PURPOSE OF REVIEW: Human islet isolation and autotransplantation [autologous islet transplant (AUTX)] is performed to prevent or ameliorate brittle diabetes after total pancreatectomy performed for benign disease. The success or failure of the transplant can be associated with a profound impact on the individual's quality of life and even survival. AUTX offers unique insights into the effects of pancreas quality, islet number, isolation technique and alternate site engraftment on transplant efficacy...
August 2017: Current Opinion in Organ Transplantation
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