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Islet cell transplantation

Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
We tested whether exposure of beta cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike...
October 20, 2016: Islets
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
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
Kevin V Chow, Emma M Carrington, Yifan Zhan, Andrew M Lew, Robyn M Sutherland
Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2...
October 13, 2016: Cell Transplantation
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Riccardo Calafiore, Giuseppe Basta, Pia Montanucci
Microencapsulation technology, based on use of alginic acid biopolymers, has been devised many years ago. However, when intended for enveloping human islets for transplantation purposes, the method needs to be up-scaled and implemented with care being taken to comply with simple but important measures. It is almost indispensable to rely on an ultrapurified alginic polymers: in fact, any, even minimal, alginate contamination with endotoxins, pyrogens, and proteins could provoke the host's inflammatory reaction upon graft, with heavy adverse consequences on the capsules immunoprotective properties, hence on graft survival per se...
2017: Methods in Molecular Biology
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
Youngjin Kim, Hyeongseok Kim, Ung Hyun Ko, Youjin Oh, Ajin Lim, Jong-Woo Sohn, Jennifer H Shin, Hail Kim, Yong-Mahn Han
Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin secretion as well as therapeutic effects. Pancreatic hormone-expressing endocrine cells (ECs) were differentiated from hESCs using a step-wise protocol...
October 12, 2016: Scientific Reports
Shuyun Liu, Lanlan Zhang, Jingqiu Cheng, Yanrong Lu, Jingping Liu
Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated...
2016: International Journal of Nanomedicine
Ka Hei Chan, Rahul Krishnan, Michael Alexander, Jonathan Rt Lakey
The islets of Langerhans are endocrine tissue clusters that secrete hormones that regulate the body's glucose, carbohydrate and fat metabolism, the most important of which is insulin, a hormone secreted by β cells within the islets. In certain instances, a person's own immune system attacks and destroys them leading to the development of Type 1 diabetes (T1D), a lifelong condition that needs daily insulin administration to maintain health and prolong survival. Islet transplantation is a surgical procedure that has demonstrated the ability to normalize blood sugar levels for up to a few years, but the need for chronic immunosuppression relegates it to a last resort that is often only used sparingly, and in seriously-ill patients...
October 10, 2016: Cell Transplantation
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
Junbi Xv, Qianwen Ming, Xiaotong Wang, Wenjing Zhang, Zheng Li, Shuai Wang, Yulin Li, Lisha Li
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by lack of insulin and irreversible destruction of islet β cells. In order to alleviate the symptoms, lifelong exogenous insulin administration has been the primary treatment of T1DM. In recent years, as a novel promising therapy, the transplantation of mesenchymal stem cells (MSCs) with or without pancreatic islets has achieved great therapeutic effects in animal models due to their multipotency along with their secretion of cytokines, angiogenic factors and immunomodulatory substances...
October 10, 2016: Cell and Tissue Research
Junfeng Li, Johann Karunananthan, Bradley Pelham, Fouad Kandeel
It was estimated that every year more than 30000 persons in the United States - approximately 80 people per day - are diagnosed with type 1 diabetes (T1D). T1D is caused by autoimmune destruction of the pancreatic islet (β cells) cells. Islet transplantation has become a promising therapy option for T1D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography (PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism...
September 28, 2016: World Journal of Radiology
Hiroshi Nomoto, Hideaki Miyoshi, Tomoo Furumoto, Koji Oba, Hiroyuki Tsutsui, Atsushi Inoue, Tatsuya Atsumi, Naoki Manda, Yoshio Kurihara, Shin Aoki
OBJECTIVES: The DPP-4 inhibitors are incretin-related drugs that improve hyperglycemia in a glucose-dependent manner and have been reported to exert favorable effects on atherosclerosis. However, it has not been fully elucidated whether DPP-4 inhibitors are able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with that of the sulfonylurea glimepiride...
2016: PloS One
João Paulo M C M Cunha, Gunter Leuckx, Peter Sterkendries, Hannelie Korf, Gabriela Bomfim-Ferreira, Lutgart Overbergh, Bart Vaes, Harry Heimberg, Conny Gysemans, Chantal Mathieu
AIMS/HYPOTHESIS: Hypoxia in the initial days after islet transplantation leads to considerable loss of islet mass and contributes to disappointing outcomes in the clinical setting. The aim of the present study was to investigate whether co-transplantation of human non-endothelial bone marrow-derived multipotent adult progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic growth factors during the initial days after implantation, could improve islet engraftment and survival...
October 4, 2016: Diabetologia
Anna M Knapinska, Sabrina Amar, Zhong He, Sandro Matosevic, Claudia Zylberberg, Gregg B Fields
Cell isolation methods for therapeutic purposes have seen little advancement over the years. The original methods of stem cell and islet isolation using bacterial collagenases were developed in the early 1980s and are still used today. Bacterial collagenases are subject to autodegradation, and isolates obtained with these enzymes may be contaminated with endotoxins, reducing cell viability and contributing to toxicity in downstream applications. Here we describe a novel method for isolation of mesenchymal stem cells from adipose tissue (ADSC) utilizing recombinantly produced matrix metalloproteases (MMPs)...
November 2016: Enzyme and Microbial Technology
R Roat, M M Hossain, J Christopherson, C Free, S Jain, C Guay, R Regazzi, Z Guo
Currently there is no effective approach for monitoring early β cell loss during islet graft rejection following human islet transplantation (HIT). Due to ethical and technical constraints, it is difficult to directly study biomarkers of islet destruction in humans. Here, we established a humanized mouse model with induced human β cell death using adoptive lymphocyte transfer (ALT). Human islet grafts of ALT-treated mice had peri-graft lymphocyte infiltration, fewer insulin(+) β cells, and increased β cell apoptosis...
October 3, 2016: American Journal of Transplantation
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
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