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Pancreatic islet transplantation

Maria Csobonyeiova, Stefan Polak, Lubos Danisovic
Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent destruction of the insulin-secreting β-cells in pancreatic islets, resulting in a deficiency of the glucose-lowering hormone insulin and persisting high blood glucose levels. Insulin has to be replaced by regular subcutaneous injections, and blood glucose level must be monitored due to the risk of hyperglycemia. Recently, transplantation of new pancreatic β-cells into T1D patients has come to be considered one of the most potentially effective treatments for this disease...
August 16, 2018: Experimental and Clinical Endocrinology & Diabetes
Florence Renaud, Mikael Chetboun, Julien Thevenet, Nathalie Delalleau, Valery Gmyr, Thomas Hubert, Caroline Bonner, Mathieu Messager, Emmanuelle Leteurtre, Christophe Mariette, Julie Kerr-Conte, Guillaume Piessen, François Pattou
BACKGROUND: total pancreatectomy with intraportal islet autotransplantation (TPIAT) rather than partial pancreatectomy could represent a major shift in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC) when risks of postoperative pancreatic fistula are well identified. This approach provides a theoretical risk of tumor cell dissemination when islet cells are transplanted into the portal vein. Our objective was to demonstrate the safety of TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of human cells isolated from pancreatic specimen during partial pancreatectomy performed for PDAC...
August 15, 2018: Transplantation
Brett A Johnson, Margaret Coutts, Hillary M Vo, Xinya Hao, Nida Fatima, Maria J Rivera, Robert J Sims, Michael J Neel, Young-Jin Kang, Edwin S Monuki
BACKGROUND: Choroid plexus epithelial cells express high levels of transthyretin, produce cerebrospinal fluid and many of its proteins, and make up the blood-cerebrospinal fluid barrier. Choroid plexus epithelial cells are vital to brain health and may be involved in neurological diseases. Transgenic mice containing fluorescent and luminescent reporters of these cells would facilitate their study in health and disease, but prior transgenic reporters lost expression over the early postnatal period...
August 16, 2018: Fluids and Barriers of the CNS
Edith J Arany, Muhammad Waseem, Brenda J Strutt, Astrid Chamson-Reig, Adam Bernardo, Elizabeth Eng, David J Hill
Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) improve glycemic control in diabetic mice, but their kinetics and associated changes in pancreatic morphology have not been directly compared. Our goal was to examine the time course of improvements in glucose tolerance and associated changes in β-cell mass and proliferation following transplantation of equivalent numbers of HSC or MSC from the same bone marrow into diabetic non-obese diabetic severe combined immune deficiency (NOD...
August 15, 2018: Islets
Takayuki Anazawa, Hideaki Okajima, Shinji Uemoto
No abstract text is available yet for this article.
2018: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
Rehana Akter, Rebekah L Bower, Andisheh Abedini, Ann Marie Schmidt, Debbie L Hay, Daniel P Raleigh
Islet amyloid formation contributes to β-cell death and dysfunction in type-2 diabetes and to the failure of islet transplants. Amylin (Islet amyloid polypeptide, IAPP), a normally soluble 37 residue polypeptide hormone produced in the pancreatic β-cells, is responsible for amyloid formation in type-2 diabetes. The peptide is deficient in type-1 diabetes. Amylin normally plays an adaptive role in metabolism and the development of non-toxic, non-amyloidogenic, bioactive variants of human amylin are of interest for use as adjuncts to insulin therapy...
August 7, 2018: ACS Chemical Biology
Rita Sofia Garcia Ribeiro, Conny Gysemans, João Paulo Monteiro Carvalho Mori da Cunha, Bella B Manshian, Daniel Jirak, Jan Kriz, Juan Gallo, Manuel Bañobre-López, Tom Struys, Marcel De Cuyper, Chantal Mathieu, Stefaan J Soenen, Willy Gsell, Uwe Himmelreich
Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity. In vivo experiments showed that pancreatic islets (50-1000 units) labeled with MLs were detectable for up to 6 weeks post-transplantation in the kidney subcapsular space...
July 31, 2018: Scientific Reports
Stephen J Hughes, Paul A Bateman, Sarah E Cross, Daniel Brandhorst, Heide Brandhorst, Ioannis Spiliotis, Chitra Ballav, Miranda Rosenthal, Martin K Rutter, James Shaw, Stephen Gough, Paul R V Johnson
BACKGROUND: It has been proposed that islet transplants comprised primarily of small rather than large islets may provide better graft function, due to their lower susceptibility to hypoxic damage. Our aim was to determine whether islet size correlated with in vivo graft function in islet transplant recipients with C peptide negative type 1 diabetes when islets have undergone pretransplant islet culture. METHODS: Human pancreatic islets were isolated, cultured for 24hours and infused by standardised protocols...
July 30, 2018: Transplantation
Kayoung Lee, Jaeyoon Kim, Martin Köhler, Jia Yu, Yue Shi, Shao-Nian Yang, Sung Ho Ryu, Per-Olof Berggren
Voltage-gated Ca2+ channels (Cav ) are essential for pancreatic beta cell function as they mediate Ca2+ influx, which leads to insulin exocytosis. The β3 subunit of Cav (Cav β3 ) has been suggested to regulate cytosolic Ca2+ ([Ca2+ ]i ) oscillation frequency and insulin secretion under physiological conditions, but its role in diabetes is unclear. Here, we report that islets from diabetic mice show Cav β3 overexpression, altered [Ca2+ ]i dynamics, and impaired insulin secretion upon glucose stimulation. Consequently, in high-fat diet (HFD)-induced diabetes, Cav β3 -deficient (Cav β3 -/- ) mice showed improved islet function and enhanced glucose tolerance...
July 24, 2018: Cell Reports
Yoshinobu Takahashi, Takanori Takebe, Hideki Taniguchi
Despite the promise of emerging organoid-based approaches, building additional complexity, such as the vascular network, remains a major challenge toward regenerative therapy. Recently, we developed a complex organoid engineering method by "self-condensation," wherein mesenchymal cell-dependent contraction enables large-scale condensation from heterotypic multiple progenitors. Here, we describe the adaptation of this protocol for generating three-dimensional (3D) pancreatic condensates from dissociated β cell lines (MIN6) together with blood vessel-forming progenitors...
May 2018: Current Protocols in Stem Cell Biology
Kuo-Cheng Lan, Ching-Chia Wang, Yuan-Peng Yen, Rong-Sen Yang, Shing-Hwa Liu, Ding-Cheng Chan
A population of muscle-derived stem/progenitor cells (MDSPCs) contained in skeletal muscle is responsible for muscle regeneration. MDSPCs from mouse muscle have been shown to be capable of differentiating into pancreatic islet-like cells. However, the potency of MDSPCs to differentiate into functional islet-like cluster remains to be confirmed. The therapeutic potential of autologous MDSPCs transplantation on type 1 diabetes still remains unclear. Here, we investigated a four-stage method to induce the differentiation of MDSPCs into insulin-producing clusters in vitro, and tested the autologous transplantation to control type 1 diabetes in mice...
July 23, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Anil Dangi, Shuangjin Yu, Xunrong Luo
PURPOSE OF REVIEW: This article is aimed to provide readers with an updated review on the applicability, efficacy, and challenges of employing donor apoptotic cell-based therapies to promote transplantation tolerance in various experimental and clinical settings. RECENT FINDINGS: Recently, donor apoptotic cell-based therapies have been employed in various models of cell (including pancreatic islets and bone marrow hematopoietic stem cells) and solid organ (heart and kidney) transplantation to promote donor-specific tolerance...
July 17, 2018: Current Opinion in Organ Transplantation
Farooq Syed, Marco Bugliani, Michela Novelli, Francesco Olimpico, Mara Suleiman, Lorella Marselli, Ugo Boggi, Franco Filipponi, Vittoria Raffa, Silke Krol, Daniela Campani, Pellegrino Masiello, Vincenzo De Tata, Piero Marchetti
To improve the efficiency of pancreatic islet transplantation, we performed in-vitro and in-vivo experiments with isolated human pancreatic islets coated by multi-layer nano-encapsulation using differently charged polymers [chitosan and poly(sodium styrene sulfonate)] to obtain up to 9 layers. The islet coating (thickness: 104.2 ± 4.2 nm) was uniform, with ≥ 90% cell viability and well preserved beta- and alpha-cell ultrastructure. Nano-encapsulated islets maintained physiological glucose-stimulated insulin secretion by both static incubation and perifusion studies...
July 23, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Cheng Xiang, Qiu-Ping Xie
Ectogenic pancreatic islet transplantation has long been discussed as having the potential to reverse diabetes. The aim of the present study was to evaluate the therapeutic efficacy of co‑transplantation with hypoxia pretreated mesenchymal stem cells (MSCs) and islets in a diabetic mouse model. MSCs were isolated from femoral and tibial bone marrow aspirates from female BALB/c donor mice. MSC proliferation rates and the expression levels of vascular endothelial growth factor A (VEGFA), interleukin (IL)‑6, monocyte chemoattractant protein (MCP)‑1 and matrix metalloproteinase (MMP)‑9 were measured in hypoxic conditions...
September 2018: Molecular Medicine Reports
O V Kokorev, V N Khodorenko, S G Anikeev, V E Gunter
The dynamics of the development of the pancreatic islet cells in the porous TiNi scaffold was studied by electron microscopy. Changes in the metabolism of glucose and glycosylated hemoglobin and parameters of the peripheral blood and bone marrow were shown after transplantation of pancreatic islet cells on porous permeable TiNi scaffold during alloxan-induced diabetes. The cells administered on the porous biocompatible scaffold produced more prolonged anti-diabetic effect and normalized hemopoiesis parameters in comparison with their intraperitoneal administration...
July 13, 2018: Bulletin of Experimental Biology and Medicine
Anaïs Schaschkow, Séverine Sigrist, Carole Mura, Caroline Dissaux, Karim Bouzakri, Anne Lejay, Catherine Bruant-Rodier, Michel Pinget, Elisa Maillard
Following the tremendous development of hydrogels for cell therapy, there is now a growing need for surgical techniques to validate in vivo scaffold benefits for islet transplantation. Therefore, we propose a newly designed surgical procedure involving the injection of hydrogel-embedded pancreatic islets in the omentum, which is considered a favorable environment for cell survival and function. Our technique, called h-Omental Matrix Islet filliNG (hOMING) was designed to test the benefits of hydrogel on islet survival and function in vivo...
January 1, 2018: Cell Transplantation
Sara Dutton Sackett, Daniel M Tremmel, Fengfei Ma, Austin K Feeney, Rachel M Maguire, Matthew E Brown, Ying Zhou, Xiang Li, Cori O'Brien, Lingjun Li, William J Burlingham, Jon S Odorico
Extracellular matrix (ECM) plays an important developmental role by regulating cell behaviour through structural and biochemical stimulation. Tissue-specific ECM, attained through decellularization, has been proposed in several strategies for tissue and organ replacement. Decellularization of animal pancreata has been reported, but the same methods applied to human pancreas are less effective due to higher lipid content. Moreover, ECM-derived hydrogels can be obtained from many decellularized tissues, but methods have not been reported to obtain human pancreas-derived hydrogel...
July 11, 2018: Scientific Reports
Muhammad R Haque, Jee-Heon Jeong, Kyo Won Lee, Du Yeon Shin, Geun-Soo Kim, Sung Joo Kim, Youngro Byun
The microenvironment of pancreatic islets gets disrupted during enzyme digestion and causes islets to remain in vulnerable state, leading to poor outcome in the initial days of transplantation. To avoid immune invasion while allowing the reconstruction of microenvironment of the transplanted site, we propose immunoisolation polymers, which can nano-encapsulate islets quickly without cytotoxicity. Here, non-human primate (NHP) islets were nano-encapsulated with hyperbranched polyethylene glycol (hb-PEG) and heparin by layer-by-layer technology and transplanted into the kidney subcapsular space of diabetic C57BL/6 mice...
July 9, 2018: Bioconjugate Chemistry
Jingyi Yang, Shaofeng Lou, Deling Kong, Chen Li
Cell surface engineering can protect implanted cells from host immune attack. It can also reshape cellular landscape to improve graft function and survival post-transplantation. This protocol aims to achieve surface engineering of pancreatic islets using an ultrathin heparin-incorporated starPEG (Hep-PEG) nanocoating. To generate the Hep-PEG nanocoating for pancreatic islet surface engineering, heparin succinimidyl succinate (Heparin-NHS) was first synthesized by modification of its carboxylate groups using N-(3-dimethylamino propyl)-N'-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS)...
June 23, 2018: Journal of Visualized Experiments: JoVE
Alban Zarzavadjian Le Bian, Manuela Cesaretti, Nicolas Tabchouri, Philippe Wind, David Fuks
BACKGROUND: With an increasing postoperative survival and prolonged follow-up, late complications following pancreaticoduodenectomy (PD) have yet to be thoroughly described and analyzed. Among those, pancreatic anastomosis stricture may lead to severe consequences. METHODS: A systematic review focusing on pancreaticojejunostomy anastomosis (PJA) stricture. RESULTS: PJA stricture incidence reached 1.4-11.4% with a median time interval of 34 months after PD...
July 6, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
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