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Pancreas cells transplantation

Kathrin Fielitz, Kristina Althoff, Katleen De Preter, Julie Nonnekens, Jasmin Ohli, Sandra Elges, Wolfgang Hartmann, Günter Klöppel, Thomas Knösel, Marc Schulte, Ludger Klein-Hitpass, Daniela Beisser, Henning Reis, Annette Eyking, Elke Cario, Johannes H Schulte, Alexander Schramm, Ulrich Schüller
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland...
October 19, 2016: Oncotarget
Jamal Mohammadi Ayenehdeh, Bahareh Niknam, Seyed Mahmoud Hashemi, Hossein Rahavi, Nima Rezaei, Masoud Soleimani, Nader Tajik
BACKGROUND: Islet transplantation could be an ideal alternative treatment to insulin therapy for type 1 diabetes Mellitus (T1DM). This clinical and experimental field requires a model that covers problems such as requiring a large number of functional and viable islets, the optimal transplantation site, and the prevention of islet dispersion. Hence, the methods of choice for isolation of functional islets and transplantation are crucial. METHODS: The present study has introduced an experimental model that overcomes some critical issues in islet transplantation, including in situ pancreas perfusion by digestive enzymes through common bile duct...
October 18, 2016: Iranian Biomedical Journal
M H Park, S Kim, H Hwang, H Park, J Kwak, E K Kwon, H Y Sung, B Han
OBJECTIVE: For deceased-donor organ transplantations, negative T cell crossmatches (XMs) are mandatory for kidney and pancreas allocation in the Korean Network for Organ Sharing (KONOS) organ allocation system. Submission and periodic renewal of serum to the KONOS is required for all transplantation candidates of kidney or pancreas and these sera are distributed to 23 laboratories for preliminary XMs. We have investigated how sensitization status varies among transplantation candidates waitlisted for different organs...
September 2016: Transplantation Proceedings
Kevin Enck, John Patrick McQuilling, Giuseppe Orlando, Riccardo Tamburrini, Sittadjody Sivanandane, Emmanuel C Opara
Islet transplantation (IT) has recently been shown to be a promising alternative to pancreas transplantation for reversing diabetes. IT requires the isolation of the islets from the pancreas, and these islets can be used to fabricate a bio-artificial pancreas. Enzymatic digestion is the current gold standard procedure for islet isolation but has lingering concerns. One such concern is that it has been shown to damage the islets due to nonselective tissue digestion. This chapter provides a detailed description of a nonenzymatic method that we are exploring in our lab as an alternative to current enzymatic digestion procedures for islet isolation from human and nonhuman pancreatic tissues...
2017: Methods in Molecular Biology
Varna Sharma, Michael Hunckler, Melur K Ramasubramanian, Emmanuel C Opara, Kalyan C Katuri
Bioartificial pancreas made of insulin-secreting islets cells holds great promise in the treatment of individuals with Type-1 diabetes. Successful islet cell microencapsulation in biopolymers is a key step for providing immunoisolation of transplanted islet cells. Because of the variability in the size and shape of pancreatic islets, one of the main obstacles in their microencapsulation is the inability to consistently control shape, size, and microstructure of the encapsulating biopolymer capsule. In this chapter, we provide a detailed description of a microfluidic approach to islet cell encapsulation in alginate that might address the microencapsulation challenges...
2017: Methods in Molecular Biology
Cornelis R van der Torren, Jessica S Suwandi, DaHae Lee, Ernst-Jan T van 't Wout, Gaby Duinkerken, Godelieve Swings, Arend Mulder, Frans H J Claas, Zhidong Ling, Pieter Gillard, Bart Keymeulen, Peter In 't Veld, Bart O Roep
Transplantation of islet allografts into type 1 diabetic recipients usually requires multiple pancreas donors to achieve insulin independence. This adds to the challenges of immunological monitoring of islet transplantation currently relying on surrogate immune markers in peripheral blood. We investigated donor origin and infiltration of islets transplanted in the liver of a T1D patient who died of hemorrhagic stroke four months after successful transplantation with two intraportal islet grafts combining six donors...
October 10, 2016: Cell Transplantation
Sumeeta Khurana, Nitya Batra
Toxoplasmosis in organ transplant patients can be a result of donor-transmitted infection, or reactivation of latent infection, or de novo infection. Solid organ transplants including heart, liver, kidney, pancreas and small bowel, and hematogenous stem cell transplants have been implicated in the risk of acquiring infection. In contrast to a benign course in immunocompetent individuals, the spectrum of illness is severe in transplant recipients. Clinical manifestations usually occur within the first 3 months of transplant and may present as encephalitis, pneumonitis, chorioretinitis, meningitis, and disseminated toxoplasmosis with multi-organ involvement...
July 2016: Tropical Parasitology
R Girlanda, A Pozzi, C S Matsumoto, T M Fishbein
Organ transplantation in patients with prior malignancy increases the risk of tumor recurrence post-transplantation due to immunosuppression. Only two cases of liver transplantation have so far been reported in children with hepatic metastases from pancreatoblastoma, a rare malignant neoplasm originating from the epithelial exocrine cells of the pancreas. Herein, we describe a case of a successful multi-visceral transplant in a man with intestinal failure after surgical resection of pancreatoblastoma.
2016: International Journal of Organ Transplantation Medicine
Hang Zhao, Zhiying He, Dandan Huang, Jun Gao, Yanfang Gong, Hongyu Wu, Aifang Xu, Xiangjun Meng, Zhaoshen Li
Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection...
2016: Stem Cells International
Hong-Tu Li, Fang-Xu Jiang, Ping Shi, Tao Zhang, Xiao-Yu Liu, Xue-Wen Lin, Zhong-Yan San, Xi-Ning Pang
Islet transplantation provides curative treatments to patients with type 1 diabetes, but donor shortage restricts the broad use of this therapy. Thus, generation of alternative transplantable cell sources is intensively investigated worldwide. We previously showed that bone marrow-derived mesenchymal stem cells (bmMSCs) can be reprogrammed to pancreatic-like cells through simultaneously forced suppression of Rest/Nrsf (repressor element-1 silencing transcription factor/neuronal restrictive silencing factor) and Shh (sonic hedgehog) and activation of Pdx1 (pancreas and duodenal transcription factor 1)...
October 3, 2016: In Vitro Cellular & Developmental Biology. Animal
Nancy El-Hossary, Hamdy Hassanein, Abdel Wahab El-Ghareeb, Hisham Issa
AIM: To evaluate the efficiency of mesenchymal stem cells isolated from Wharton's jelly (WJ-MSCs) through either the intravenous or intraperitoneal transplantations into streptozotocin (STZ)-induced diabetic rats as a therapy for type 1 diabetes mellitus (T1DM). METHODOLOGY: A rat model with STZ induction was established and the rats were divided into 3 groups: a tail vein injection group, an intraperitoneal injection group and a STZ control group. Following transplantation, blood glucose levels were monitored weekly then the pancreatic tissues were collected to examine the pancreatic islets by histopathology and morphometric studies...
September 21, 2016: Diabetes Research and Clinical Practice
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Hyun-Je Kim, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Sang-Man Jin, Chung-Gyu Park
BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months...
September 27, 2016: Xenotransplantation
Orit Markowitz, Michelle Schwartz
Immunosuppressed transplant recipients have increased risk for the development of basal cell carcinoma skin cancers. While oral vismodegib therapy has been successful in treating locally advanced basal cell tumors, few studies document its use and efficacy in organ transplant patients. In this immunocompromised population, topical imiquimod 5% cream has been shown to be an effective and well-tolerated option for superficial and nodular basal cell carcinomas. To the authors' knowledge, no data documents the use of optical coherence tomography, a noninvasive imaging technique, to monitor progress of such combined therapies on in vivo skin...
August 2016: Journal of Clinical and Aesthetic Dermatology
Issei Saitoh, Masahiro Sato, Miki Soda, Emi Inada, Yoko Iwase, Tomoya Murakami, Hayato Ohshima, Haruaki Hayasaki, Hirofumi Noguchi
Type 1 diabetes occurs due to the autoimmune destruction of pancreatic β-cells in islets. Transplantation of islets is a promising option for the treatment of patients with type 1 diabetes that experience hypoglycemic unawareness despite maximal care, but the present shortage of donor islets hampers such transplantation. Transplantation of insulin-producing cells derived from the patients themselves would be one of the most promising approaches to cure type 1 diabetes. Previously, we demonstrated that insulin-producing cells could be produced by transfecting murine pancreatic cells with Yamanaka's reprogramming factors...
2016: PloS One
Gabriel Fernandes-Silva, Mayara Ivani de Paula, Érika B Rangel
INTRODUCTION: Patient and pancreas allograft survival improved following reductions in surgical complications, tighter donor selection and optimization in immunosuppressive protocols. However, long-term survival of pancreas allografts is adversely affected by rejection and immunosuppressive regimen toxicity. AREAS COVERED: This article reviews the existing literature and knowledge of mammalian target of rapamycin inhibitors (mTORi). Some clinically relevant drug-drug interactions are highlighted...
September 23, 2016: Expert Opinion on Drug Metabolism & Toxicology
Meike Hohwieler, Anett Illing, Patrick C Hermann, Tobias Mayer, Marianne Stockmann, Lukas Perkhofer, Tim Eiseler, Justin S Antony, Martin Müller, Susanne Renz, Chao-Chung Kuo, Qiong Lin, Matthias Sendler, Markus Breunig, Susanne M Kleiderman, André Lechel, Martin Zenker, Michael Leichsenring, Jonas Rosendahl, Martin Zenke, Bruno Sainz, Julia Mayerle, Ivan G Costa, Thomas Seufferlein, Michael Kormann, Martin Wagner, Stefan Liebau, Alexander Kleger
OBJECTIVE: The generation of acinar and ductal cells from human pluripotent stem cells (PSCs) is a poorly studied process, although various diseases arise from this compartment. DESIGN: We designed a straightforward approach to direct human PSCs towards pancreatic organoids resembling acinar and ductal progeny. RESULTS: Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultrastructural, global gene expression and functional hallmarks of the human pancreas in the dish...
September 15, 2016: Gut
Cynthia M Stonnington, Betty Darby, Angela Santucci, Pamela Mulligan, Patricia Pathuis, Andrea Cuc, Joseph G Hentz, Nan Zhang, David Mulligan, Amit Sood
Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience...
September 12, 2016: Clinical Transplantation
Keiko Omori, Eiji Kobayashi, Jeffrey Rawson, Masafumi Takahashi, Yoko Mullen
Prolonged pancreas cold ischemia is known to negatively correlate with islet isolation outcomes, hindering successful islet transplantation to treat Type-1 Diabetes. Due to poor islet isolation outcome, pancreata with over 16 h cold ischemia are currently not considered for islet transplantation. Mechanisms involved in pancreas cold ischemia/rewarming mediated islet damage during islet isolation and culture are not well understood. Using an en bloc cold preserved rat pancreas preparation, we attempted to clarify possible mechanisms of islet death associated with prolonged pancreas cold ischemia and subsequent rewarming...
October 2016: Cryobiology
Wayne J Hawthorne, Lindy Williams, Yi Vee Chew
The overarching success of islet transplantation relies on the success in the laboratory to isolate the islets. This chapter focuses on the processes of human islet cell isolation and the ways to optimally provide islet cells for transplantation. The major improvements in regards to the choice of enzyme type, way the digested pancreas tissue is handled to best separate islets from the acinar and surrounding tissues, the various methods of purification of the islets, their subsequent culture and quality assurance to improve outcomes to culminate in safe and effective islet transplantation will be discussed...
2016: Advances in Experimental Medicine and Biology
Wayne J Hawthorne
For more than two decades we have been refining advances in islet cell transplantation as a clinical therapy for patients suffering from type 1 diabetes. A great deal of effort has gone to making this a viable therapy for a broader range of patients with type 1 diabetes. Clinical results have progressively improved, demonstrating clinical outcomes on par with other organ transplants, specifically in terms of insulin independence, graft and patient survival. We are now at the point where islet cell transplantation, in the form of allotransplantation, has become accepted as a clinical therapy in adult patients affected by type 1 diabetes, in particular those suffering from severe hypoglycaemic unawareness...
2016: Advances in Experimental Medicine and Biology
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