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pancreatic Transplant

Cindy J M Loomans, Nerys Williams Giuliani, Jeetindra Balak, Femke Ringnalda, Léon van Gurp, Meritxell Huch, Sylvia F Boj, Toshiro Sato, Lennart Kester, Susana M Chuva de Sousa Lopes, Matthias S Roost, Susan Bonner-Weir, Marten A Engelse, Ton J Rabelink, Harry Heimberg, Robert G J Vries, Alexander van Oudenaarden, Françoise Carlotti, Hans Clevers, Eelco J P de Koning
Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi ), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue...
March 13, 2018: Stem Cell Reports
Rita Sofia Garcia Ribeiro, Ashwini Ketkar-Atre, Ting Yin, Karim Louchami, Tom Struys, Ivo Lambrichts, Abdullah Sener, Willy Jean Malaisse, Marcel De Cuyper, Uwe Himmelreich
Pancreatic islets (PIs) transplantation is an alternative approach for the treatment of severe forms of type 1 diabetes (T1D). To monitor the success of transplantation, it is desirable to follow the location of engrafted PIs non-invasively. In vivo magnetic resonance imaging (MRI) of transplanted PIs is a feasible cell tracking method; however, this requires labeling with a suitable contrast agent prior to transplantation. We have tested the feasibility of cationic magnetoliposomes (MLs), compared to commercial contrast agents (Endorem and Resovist), by labeling insulinoma cells and freshly isolated rat PIs...
March 12, 2018: Journal of Personalized Medicine
Zhimin Tao, Mandar Deepak Muzumdar, Alexandre Detappe, Xing Huang, Eric Xu, Yingjie Yu, Tarek H Mouhieddine, Haiqin Song, Tyler Jacks, P Peter Ghoroghchian
Human pancreatic ductal adenocarcinoma (PDAC) contains a distinctively dense stroma that limits the accessibility of anticancer drugs, contributing to its poor overall prognosis. Nanoparticles can enhance drug delivery and retention in pancreatic tumors and have been utilized clinically for their treatment. In preclinical investigations, various mouse models differentially recapitulate the microenvironmental features of human PDAC. Here, we demonstrate that through utilization of different organic co-solvents and by doping of a homopolymer of poly(ε-caprolactone), a diblock copolymer composition of poly(ethylene oxide)- block-poly(ε-caprolactone) may be utilized to generate biodegradable and nanoscale micelles with different physical properties...
March 13, 2018: Nano Letters
Francis D Gratte, Sara Pasic, John K Olynyk, George C T Yeoh, David Tosh, Deirdre R Coombe, Janina E E Tirnitz-Parker
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium...
March 12, 2018: Scientific Reports
Andrew A Gumbs, Despoina Daskalaki, Luca Milone
Although minimally invasive pancreatectomy has been performed increasingly for pancreatic malignancies, many authors feel that a history of pancreatitis is a contraindication to either laparoscopic or robotic-assisted pancreatectomy. Shown here is a video (Supplemental Digital Content 1, of a laparoscopic total pancreatectomy with splenectomy for chronic pancreatitis. This patient was denied auto-islet cell transplantation because of insurance restraints. In total, 4 laparoscopic total pancreatectomies have been attempted and completed...
March 8, 2018: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques
Olga Ulyanova, Abay Baigenzhin, Zhaksylyk Doskaliyev, Temirlan Karibekov, Larissa Kozina, Samat Saparbayev, Rakhat Trimova
OBJECTIVES: Our objective was to determine transforming growth factor β1 levels in patients with type 2 diabetes mellitus after fetal pancreatic stem cell transplant. MATERIALS AND METHODS: We examined 10 patients (age range, 41-65 y) with type 2 diabetes mellitus, which we subsequently divided into 2 groups. Group 1 comprised 5 patients who received fetal pancreatic stem cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion. Group 2 comprised 5 patients (control group) who were on hypoglycemic tablet therapy or insulin therapy...
March 2018: Experimental and Clinical Transplantation
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
March 7, 2018: Biochemical and Biophysical Research Communications
Zubaidah Nor Hanipah, Suriya Punchai, Stacy A Brethauer, Philip R Schauer, Ali Aminian
INTRODUCTION: While bariatric surgery leads to significant prevention and improvement of type 2 diabetes, patients may rarely develop diabetes after bariatric surgery. The aim of this study was to determine the incidence and the characteristic of new-onset diabetes after bariatric surgery over a 17-year period at our institution. METHODS: Non-diabetic patients who underwent bariatric surgery at a single academic center (1997-2013) and had a postoperative glycated hemoglobin (HbA1c) ≥ 6...
March 9, 2018: Obesity Surgery
Rayner Rodriguez-Diaz, R Damaris Molano, Jonathan R Weitz, Midhat H Abdulreda, Dora M Berman, Barbara Leibiger, Ingo B Leibiger, Norma S Kenyon, Camillo Ricordi, Antonello Pileggi, Alejandro Caicedo, Per-Olof Berggren
Every animal species has a signature blood glucose level or glycemic set point. These set points are different, and the normal glycemic levels (normoglycemia) of one species would be life threatening for other species. Mouse normoglycemia can be considered diabetic for humans. The biological determinants of the glycemic set point remain unclear. Here we show that the pancreatic islet imposes its glycemic set point on the organism, making it the bona fide glucostat in the body. Moreover, and in contrast to rodent islets, glucagon input from the alpha cell to the insulin-secreting beta cell is necessary to fine-tune the distinctive human set point...
March 6, 2018: Cell Metabolism
Arianne Aslamy, Eunjin Oh, Miwon Ahn, Abu Saleh Md Moin, Mariann Chang, Molly Duncan, Jeannette Hacker-Stratton, Mohamed El-Shahawy, Fouad Kandeel, Linda A DiMeglio, Debbie C Thurmond
Context: Efforts to preserve β-cell mass in the preclinical stages of type 1 diabetes (T1D) are limited by few blood-derived biomarkers of β-cell destruction. Objective: Platelets are proposed sources of blood-derived biomarkers for a variety of diseases, and they show distinct proteomic changes in T1D. Thus, we investigated changes in the exocytosis protein, double C2 domain protein-β (DOC2B) in platelets and islets from T1D humans and pre-diabetic NOD mice...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
Luis Muñoz-Bellvis, María Del Carmen Esteban, Manuel Iglesias, Luis González, Juan Ignacio González-Muñoz, Cristina Muñoz-González, José E Quiñones, Guadalupe Tabernero, Rosa Ana Iglesias, José María Sayagués, Pilar Fraile
INTRODUCTION: Simultaneous kidney-pancreas transplantation for patients with type 1 diabetes and end-stage chronic renal disease is widely performed. However, the rate of surgical morbidity from pancreatic complications remains high. The aim of this study was to describe the development and results of a new program, from the point of view of the pancreatic surgeon. METHODS: We analyzed 53 simultaneous kidney-pancreas transplantations performed over a period of seven years (2009-2016), with a median follow up of 39 months (range: 1-86 months)...
February 28, 2018: Cirugía Española
Tiziana A L Brevini, Georgia Pennarossa, Elena F M Manzoni, Fulvio Gandolfi
Type 1 Diabetes Mellitus (T1DM) is a chronic disease that leads to loss of insulin secreting β-cells, causing high levels of blood glucose. Exogenous insulin administration is not sufficient to mimic the normal function of β-cells and, consequently, diabetes mellitus often progresses and can lead to major chronic complications and morbidity. The physiological control of glucose levels can only be restored by replacing the β-cell mass.We recently developed a new strategy that allows for epigenetic conversion of dermal fibroblasts into insulin-secreting cells (EpiCC), using a brief exposure to the demethylating agent 5-aza-cytidine (5-aza-CR), followed by a pancreatic induction protocol...
March 3, 2018: Advances in Experimental Medicine and Biology
Rajesh Guruswamy Damodaran, Patrick Vermette
Diabetes Mellitus involves the loss of function and/or absolute numbers of insulin-producing β-cells in pancreatic islets. Islet transplantation is currently being investigated as a potential cure, and advances in tissue engineering methods can be used to improve pancreatic islets survival and functionality. Transplanted islets experience anoikis, hypoxia and inflammation-mediated immune response, leading to early damage and subsequent failure of the graft. Recent development in tissue engineering enables the use of decellularized organs as scaffolds for cell therapies...
March 2, 2018: Journal of Tissue Engineering and Regenerative Medicine
Vitale Miceli, Mariangela Pampalone, Giovanna Frazziano, Giuseppe Grasso, Enrico Rizzarelli, Camillo Ricordi, Anna Casu, Gioacchin Iannolo, Pier Giulio Conaldi
Islet transplantation is a valid therapeutic option for type 1 diabetes treatment. However, in this procedure one of the major problems is the oxidative stress produced during pancreatic islet isolation. The aim of our study was to evaluate potential protective effects of L-carnosine and its isomer D-carnosine against oxidative stress. We evaluated the carnosine effect on cell growth, cell death, insulin production, and the main markers of oxidative stress in rat and murine stressed beta cell lines as well as in human pancreatic islets...
February 26, 2018: Molecular and Cellular Endocrinology
M F Nijhoff, V A L Huurman, J Dubbeld, A R van Erkel, T A Rabelink, M A Engelse, E J P de Koning
Pancreatic islet isolation and transplantation are complicated procedures, indicated for a carefully selected group of patients. After isolation from the pancreas, the islets are infused into the portal vein. Allogeneic islet transplantation is performed in patients with diabetes mellitus, who suffer from severe hypoglycaemic events and/or progressive complications. One or more donor pancreases are used, which necessitates immunosuppressive treatment. In autologous islet transplantation, which is performed in patients in whom the pancreas has to be removed due to a non-malignant disease, the patients' own islets are isolated and reinfused...
2018: Nederlands Tijdschrift Voor Geneeskunde
Carmen Fotino, Diego Dal Ben, Elena Adinolfi
BACKGROUND: Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the generation, recognition and degradation of extracellular ATP and adenosine. The main actors of this system include P2X, P2Y and Adenosine Receptors, ectonucleotidases CD39 and CD73 and Adenosine Deaminase. The purinergic network recently emerged as a central player in several physiopathological conditions particularly those linked to immune system regulation including type 1 and type 2 diabetes...
February 26, 2018: Medicinal Chemistry
Yun Zhang, Garth L Warnock, Ziliang Ao, Yoo Jin Park, Nooshin Safikhan, Aziz Ghahary, Lucy Marzban
Amyloid formation in the pancreatic islets due to aggregation of human islet amyloid polypeptide (hIAPP) contributes to reduced β-cell mass and function in type 2 diabetes (T2D) and islet transplantation. Protein kinase B (PKB) signaling plays a key role in the regulation of β-cell survival, function and proliferation. In this study, we used human and hIAPP-expressing transgenic mouse islets in culture as two ex vivo models of human islet amyloid formation to: 1. Investigate the effects of amyloid formation on PKB phosphorylation in primary islet β-cells; 2...
2018: PloS One
Antonio Matrone, Alessandro Brancatella, Piero Marchetti, Enrico Vasile, Ugo Boggi, Rossella Elisei, Filomena Cetani, Claudio Marcocci, Paolo Vitti, Francesco Latrofa
Absence of neoplastic disease in the organ-recipient is required in order to allow organ transplantation. Due to its rarity, no data regarding management of patients with Multiple endocrine neoplasia type 1 (MEN1) and end-stage renal failure candidates for kidney transplantation are available. A 36 year-old man was referred to the present hospital with MEN1, with a neuroendocrine pancreatic tumor and primary hyperparathyroidism and associated Alport syndrome with end stage renal failure. The present study aimed to establish the eligibility of the patient for a kidney transplantation...
March 2018: Molecular and Clinical Oncology
Mercedes Rubio-Manzanares Dorado, Luis Miguel Marín Gómez, Daniel Aparicio Sánchez, Sheila Pereira Arenas, Juan Manuel Praena-Fernández, Juan Jose Borrero Martín, Francisco Farfán López, Miguel Ángel Gómez Bravo, Jordi Muntané Relat, Javier Padillo Ruiz
AIM: To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. METHODS: This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic)...
February 21, 2018: World Journal of Gastroenterology: WJG
Deepak Tripathi, Satyanarayana S Cheekatla, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Elwyn Welch, Ramya Sivangala Thandi, Amy R Tvinnereim, Ramakrishna Vankayalapati
CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to allografts. Here, we found that co-transplantation of allogeneic pancreatic islets with Tregs that are defective in c-Jun N-terminal kinase 1 (JNK1) signaling prolongs islet allograft survival in the liver parenchyma of chemically induced diabetic mice (CDM). Adoptively transferred JNK1-/- but not wild-type (WT) Tregs survive longer in the liver parenchyma of CDM. JNK1-/- Tregs are resistant to apoptosis and express anti-apoptotic molecules...
February 19, 2018: Scientific Reports
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