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Pancreatic islet transplantation

Abhay Srivastava, Nidheesh Dadheech, Mitul Vakani, Sarita Gupta
Pancreatic progenitors have been explored for their profound characteristics and unique commitment to generate new functional islets in regenerative medicine. Pancreatic resident endocrine progenitors (PREPs) with mesenchymal stem cell (MSC) phenotype were purified from BALB/c mice pancreas and characterized. PREPs were differentiated into mature islet clusters in vitro by activin-A and swertisin and functionally characterized. A temporal gene and protein profiling was performed during differentiation. Furthermore, PREPs were labeled with green fluorescent protein (GFP) and transplanted intravenously into streptozotocin (STZ) diabetic mice while monitoring their homing and differentiation leading to amelioration in the diabetic condition...
October 20, 2018: Journal of Cellular Physiology
Bahareh Rajaei, Mohammad Massumi, Michael Wheeler
The International Diabetic Federation estimated that 415 million adults currently have diabetes and 318 million adults had impaired glucose tolerance, putting them at high risk of developing diabetes in the future. In Type 1 Diabetes (T1D), the β cells are lost because of autoimmune reactions. Although islet transplantation has been a promising therapy for T1D, it is greatly limited by pancreatic donors. Here, we describe a protocol to generate glucose- responsive pancreatic β-like (GRPβ-L) cells from human-induced pluripotent stem (iPS) cells...
October 18, 2018: Current Protocols in Human Genetics
Wu Lv, Jialin Zhang, Ao Jiao, Bowen Wang, Baomin Chen, Jie Lin
It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors which can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP...
October 12, 2018: Canadian Journal of Physiology and Pharmacology
Elahe Hadavi, Jeroen C H Leijten, Jenny Brinkmann, Pascal Jonkheijm, Marcel Karperien, Aart Alexander van Apeldoorn
Extracellular matrix molecules play significant roles in regulating β-cell function and viability within pancreatic islets by providing mechanical and biological support, stimulating cell survival, proliferation and their endocrine function. During clinical islet transplantation the beta cell's extracellular matrix environment is degraded by enzymatic digestion. Literature suggests that interactions between islet cells and ECM molecules, such as fibronectin, collagen IV and laminin, are essential for maintaining, or stimulation of islet function and survival, and can effect differentiation and proliferation of the endocrine cells...
October 11, 2018: Tissue Engineering. Part C, Methods
Eunjin Oh, Miwon Ahn, Solomon Afelik, Thomas C Becker, Bart O Roep, Debbie C Thurmond
Syntaxin 4 (Stx4) enrichment in human and mouse islet grafts improves transplant success in reversing STZ-induced diabetes in mice, although the underlying molecular mechanisms remain elusive. Toward further understanding this, human islets and inducible transgenic mice over-expressing Stx4 selectively in the islet β-cells (βTG-Stx4) were challenged with pro-inflammatory stressors in vitro and in vivo. Remarkably, βTG-Stx4 mice resisted multiple-low dose streptozotocin (STZ)-induced loss of β-cell mass and glucose intolerance; under standard conditions glucose tolerance was enhanced, maintaining normal fasting glycemia and insulinemia...
October 10, 2018: Diabetes
Antonio Citro, Harald C Ott
PURPOSE OF REVIEW: Engineering endocrine pancreatic tissue is an emerging topic in type 1 diabetes with the intent to overcome the current limitation of β cell transplantation. During islet isolation, the vascularized structure and surrounding extracellular matrix (ECM) are completely disrupted. Once implanted, islets slowly engraft and mostly are lost for the initial avascular phase. This review discusses the main building blocks required to engineer the endocrine pancreas: (i) islet niche ECM, (ii) islet niche vascular network, and (iii) new available sources of endocrine cells...
October 2, 2018: Current Diabetes Reports
G V Rao, R Pradeep, M Sasikala, P Pavan Kumar, V V Krishna, G Mahesh Shetty, R Talukdar, M Tandan, R Jagadeesh, D Nageshwar Reddy
Pancreatectomy and autologous islet transplantation (AIT) are performed in highly specialized centers to alleviate abdominal pain and preserve endocrine function in patients with chronic pancreatitis. We aimed at initiating AIT studies in India for the first time in patients undergoing distal pancreatectomy (DP) to prevent development of diabetes. Four out of 14 chronic pancreatitis patients screened underwent DP with AIT. Pancreatectomy specimen preserved in Wisconsin solution was subjected to islet isolation employing standard protocol using collagenase V...
October 1, 2018: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Daniel M Tremmel, Jon S Odorico
Diabetes can be treated with β cell replacement therapy, where a patient is transplanted with cadaveric human islets to restore glycemic control. Despite this being an effective treatment, the process of isolating islets from the pancreas requires collagenase digestion which disrupts the islet extracellular matrix (ECM) and activates anoikis-mediated apoptosis. To improve islet survival in culture and after transplantation, the islet microenvironment may be enhanced with the addition of ECM components which are lost during isolation...
September 25, 2018: Organogenesis
Beth Schrope
First described in the early 1980s, total pancreatectomy with autologous islet cell transplantation for the treatment of chronic pancreatitis is still only offered in select centers worldwide. Indications, process details including surgery as well as islet isolation, and results are reviewed. In addition, areas for further research to optimize results are identified.
October 2018: Gastrointestinal Endoscopy Clinics of North America
Cherry S Leung, Kevin Y Yang, Xisheng Li, Vicken W Chan, Manching Ku, Herman Waldmann, Shohei Hori, Jason C H Tsang, Yuk Ming Dennis Lo, Kathy O Lui
BACKGROUND: We have previously reported an antigen-specific protocol to induce transplant tolerance and linked suppression to human embryonic stem cell (hESC)-derived tissues in immunocompetent mice through coreceptor and costimulation blockade. However, the exact mechanisms of acquired immune tolerance in this model have remained unclear. METHODS: We utilize the NOD.Foxp3hCD2 reporter mouse line and an ablative anti-hCD2 antibody to ask if CD4+ FOXP3+ regulatory T cells (Treg) are required for coreceptor and costimulation blockade-induced immune tolerance...
September 20, 2018: Genome Medicine
Aravinth P Jawahar, Siddharth Narayanan, Gopalakrishnan Loganathan, Jithu Pradeep, Gary C Vitale, Christopher M. Jones, Michael G Hughes, Stuart K Williams, Appakalai N Balamurugan
Islet cell auto-transplantation is a novel strategy for maintaining blood glucose levels and improving the quality of life in patients with chronic pancreatitis (CP). Despite the many recent advances associated with this therapy, obtaining a good yield of islet infusate still remains a pressing challenge. Reprogramming technology, by making use of the pancreatic exocrine compartment, can open the possibility of generating novel insulin-producing cells. Several lineage-tracing studies present evidence that exocrine cells undergo dedifferentiation into a progenitor-like state from which they can be manipulated to form insulin-producing cells...
September 17, 2018: Current Stem Cell Research & Therapy
A Wojtusciszyn, J Branchereau, L Esposito, L Badet, F Buron, M Chetboun, L Kessler, E Morelon, T Berney, F Pattou, P-Y Benhamou, M-C Vantyghem
While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness...
September 14, 2018: Diabetes & Metabolism
Mark J Stice, Ty B Dunn, Melena D Bellin, Mariya E Skube, Greg J Beilman
Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for selected patients with chronic pancreatitis. The portal circulation is the standard infusion site for islet transplant, but marked elevation of portal pressures may prevent complete islet infusion. Herein we report a novel technique of combined site islet autotransplantation using an omental pouch. This technique may be useful when technical limitations prevent complete intraportal transplantation. In four TPIAT recipients with intraoperative issues precluding the complete intraportal infusion of islets, an omental pouch was created to contain the remaining islet mass...
October 2018: Cell Transplantation
Bengt von Zur-Mühlen, Torbjörn Lundgren, Levent Bayman, Christian Berne, Nancy Bridges, Thomas Eggerman, Aksel Foss, Julia Goldstein, Trond Jenssen, Carl Jorns, Yvonne Morrison, Mikael Rydén, Traci Schwieger, Gunnar Tufveson, Bo Nilsson, Olle Korsgren
BACKGROUND: When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR...
September 11, 2018: Transplantation
Victor Navarro-Tableros, Chiara Gai, Yonathan Gomez, Sara Giunti, Chiara Pasquino, Maria Chiara Deregibus, Marta Tapparo, Adriana Pitino, Ciro Tetta, Maria Felice Brizzi, Camillo Ricordi, Giovanni Camussi
A potential therapeutic strategy for diabetes is the transplantation of induced-insulin secreting cells. Based on the common embryonic origin of liver and pancreas, we studied the potential of adult human liver stem-like cells (HLSC) to generate in vitro insulin-producing 3D spheroid structures (HLSC-ILS). HLSC-ILS were generated by a one-step protocol based on charge dependent aggregation of HLSC induced by protamine. 3D aggregation promoted the spontaneous differentiation into cells expressing insulin and several key markers of pancreatic β cells...
September 6, 2018: Stem Cell Reviews
M Wszola, A Berman, L Gorski, A Ostaszewska, M Serwanska-Swietek, M Krajewska, A Lipinska, A Chmura, A Kwiatkowski
BACKGROUND: Total pancreatectomy and autologous transplantation of pancreatic islets is a treatment option for patients with severe pain due to chronic pancreatitis. In the standard procedure, pancreatic islets are isolated and subsequently administered into the portal vein. In the case of patients with a history of thrombosis or at risk of thrombosis, this route of administration is not viable. Animal studies conducted in our department led to the development of a technique of endoscopic islets transplantation into the gastric submucosa...
September 2018: Transplantation Proceedings
Konstantin Bloch, Irit Gil-Ad, Alexey Vanichkin, Shay Henry Hornfeld, Michal Taler, Shira Dar, Dmitry Azarov, Pnina Vardi, Abraham Weizman
BACKGROUND: Alzheimer's disease (AD) is often associated with brain insulin resistance and peripheral metabolic dysfunctions. Recently, we developed a model of sporadic AD associated with obesity-related peripheral metabolic abnormalities in Lewis rats using intracerebroventricular administration of streptozotocin (icv-STZ). OBJECTIVE: We aimed to assess the effect of intracranially grafted pancreatic islets on cognitive and peripheral metabolic dysfunctions in the icv-STZ Lewis rats...
2018: Journal of Alzheimer's Disease: JAD
A Gálisová, V Herynek, E Swider, E Sticová, A Pátiková, L Kosinová, J Kříž, M Hájek, M Srinivas, D Jirák
PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green...
August 30, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Julien B Pujol, Eija Heikkila, Claudia Savoia, Asghar Hajibeigi, Umberto De Marchi, Pavan K Battiprolu, Orhan K Öz, El Hadji M Dioum
Pancreatic β-cell dysfunction and death contribute to the onset of diabetes, and novel strategies of β-cell function and survival under diabetogenic conditions need to be explored. We previously demonstrated that Isx9, a small molecule based on the isoxazole scaffold, drives neuroendocrine phenotypes by increasing the expression of genes required for β-cell function and improves glycemia in a model of β cell regeneration. We further investigated the role of Isx9 in β-cell survival. We find that Isx9 drives the expression of Calbindin-D28K (D28K), a key regulator of calcium homeostasis, and plays a cytoprotective role through its calcium buffering capacity in β cells...
August 27, 2018: International Journal of Molecular Sciences
Marcos Perez-Basterrechea, Manuel M Esteban, Jose A Vega, Alvaro J Obaya
Pancreatic islet transplantation is a promising alternative to whole-pancreas transplantation as a treatment of type 1 diabetes mellitus. This technique has been extensively developed during the past few years, with the main purpose of minimizing the complications arising from the standard protocols used in organ transplantation. By using a variety of strategies used in tissue engineering and regenerative medicine, pancreatic islets have been successfully introduced in host patients with different outcomes in terms of islet survival and functionality, as well as the desired normoglycemic control...
August 25, 2018: Biotechnology and Bioengineering
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