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islet,beta-cell,diabetes,stem cell

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https://www.readbyqxmd.com/read/28655312/transplantation-of-human-fetal-pancreatic-progenitor-cells-ameliorates-renal-injury-in-streptozotocin-induced-diabetic-nephropathy
#1
Yongwei Jiang, Wenjian Zhang, Shiqing Xu, Hua Lin, Weiguo Sui, Honglin Liu, Liang Peng, Qing Fang, Li Chen, Jinning Lou
BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem. OBJECTIVE: To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM...
June 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#2
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#3
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. The valproic acid, is an inhibitor of class I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
June 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28464767/heterogeneity-of-type-1-diabetes-the-effect-of-ethnicity
#4
Mustafa Tosur, Maria Jose Redondo
BACKGROUND: Most of the current understanding of type 1 diabetes (T1D) etiology and pathogenesis stemmed from studies conducted in majoritarily Non-Hispanic White (NHW) populations. However, evidence is emerging that unique mechanisms of disease may contribute to the development of T1D in individuals of Hispanic ethnicity. OBJECTIVE: We reviewed the currently available literature on genetic, immunologic, metabolic and clinical characteristics of T1D in Hispanic as compared with NHW individuals...
May 1, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#5
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28399484/the-effect-of-g-csf-and-amd3100-on-mice-treated-with-streptozotocin-expansion-of-alpha-cells-and-partial-islet-protection
#6
Yonathan Gomez, Dylana Diaz-Solano, Teresa Gledhill, Olga Wittig, Jose Cardier
Administration of streptozotocin (STZ) is one of the most used experimental models of diabetes (STZ-DT). STZ induces beta-cell damage in pancreatic islets. It is known that hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow to damaged tissues. In this work, we evaluated the effects of the hematopoietic mobilizers G-CSF (250μg/kg; for five consecutive days) and AMD3100 (5mg/kg; single s.c injection) in mice treated with STZ (175mg/kg). Mice injected with STZ showed a significant reduction in the number and area of islets and in the number of beta- and alpha-cells...
April 8, 2017: Cytokine
https://www.readbyqxmd.com/read/28363269/establishing-a-large-animal-model-for-in-vivo-reprogramming-of-bile-duct-cells-into-insulin-secreting-cells-to-treat-diabetes
#7
Caitlin M Hill, Anannya Banga, Juan E Abrahante, Ce Yuan, Lucas A Mutch, Jody Janecek, Timothy O'Brien, Melanie L Graham, James R Dutton
Type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. Both of these approaches have severe limitations. Repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures. Islet transplantation, while highly effective, is severely limited by shortage of donor organs...
June 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28321233/heterogeneity-of-the-pancreatic-beta-cell
#8
REVIEW
Giselle Dominguez Gutierrez, Jesper Gromada, Lori Sussel
The pancreatic beta cell functions as a key regulator of blood glucose levels by integrating a variety of signals in response to changing metabolic demands. Variations in beta cell identity that translate into functionally different subpopulations represent an interesting mechanism to allow beta cells to efficiently respond to diverse physiological and pathophysiological conditions. Recently, there is emerging evidence that morphological and functional differences between beta cells exist. Furthermore, the ability of novel single cell technologies to characterize the molecular identity of individual beta cells has created a new era in the beta cell field...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#9
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
February 2017: Biochimie
https://www.readbyqxmd.com/read/28000178/quercetin-potentiates-transdifferentiation-of-bone-marrow-mesenchymal-stem-cells-into-the-beta-cells-in-vitro
#10
B Miladpour, M Rasti, A A Owji, Z Mostafavipour, Z Khoshdel, A Noorafshan, F Zal
PURPOSE: Type 1 diabetes is an autoimmune disease caused by the destruction of β-cells in the pancreas. Bone marrow mesenchymal stem cells are multipotent and easy accessible adult stem cells that may provide options in the treatment of type 1 diabetes. Injured pancreatic extract can promote the differentiation of rat bone marrow mesenchymal stem cells into β-cells. We aimed to observe the effect of quercetin in differentiation and insulin secretion in β-cells. METHODS: Bone marrow mesenchymal stem cells were obtained from the tibiae of rats...
December 20, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27925205/generation-of-insulin-producing-cells-from-human-induced-pluripotent-stem-cells-using-a-stepwise-differentiation-protocol-optimized-with-platelet-rich-plasma
#11
Seyed Ehsan Enderami, Yousef Mortazavi, Masoud Soleimani, Samad Nadri, Alireza Biglari, Reyhaneh Nassiri Mansour
Studies on patient-specific human-induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet-rich plasma (PRP) that induce the hiPSCs into insulin-producing cells (IPCs). We present here a differentiation protocol consisting of five stages in two groups including protocol with PRP and without PRP...
October 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27903221/in-vitro-generated-mesenchymal-stem-cells-suitable-tools-to-target-insulin-dependent-diabetes-mellitus
#12
Shruti D Dave, Patel C N, Patel J V, Thakkar U G
A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions...
November 21, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27820660/long-term-function-and-optimization-of-mouse-and-human-islet-transplantation-in-the-subcutaneous-device-less-site
#13
Andrew R Pepper, Antonio Bruni, Rena L Pawlick, Boris Gala-Lopez, Yasmin Rafiei, John Wink, Tatsuya Kin, A M James Shapiro
Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated with intrahepatic portal cellular infusion and the scarcity of human donor pancreata. Recent progress in stem cell biology has demonstrated that the potential to expand new β cells for clinical transplantation is now a reality...
November 2016: Islets
https://www.readbyqxmd.com/read/27787618/immunogenicity-of-human-embryonic-stem-cell-derived-beta-cells
#14
Cornelis R van der Torren, Arnaud Zaldumbide, Gaby Duinkerken, Simone H Brand-Schaaf, Mark Peakman, Geert Stangé, Laura Martinson, Evert Kroon, Eugene P Brandon, Daniel Pipeleers, Bart O Roep
AIMS/HYPOTHESIS: To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. METHODS: We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27508066/genome-edited-human-stem-cell-derived-beta-cells-a-powerful-tool-for-drilling-down-on-type-2-diabetes-gwas-biology
#15
REVIEW
Nicola L Beer, Anna L Gloyn
Type 2 diabetes (T2D) is a disease of pandemic proportions, one defined by a complex aetiological mix of genetic, epigenetic, environmental, and lifestyle risk factors. Whilst the last decade of T2D genetic research has identified more than 100 loci showing strong statistical association with disease susceptibility, our inability to capitalise upon these signals reflects, in part, a lack of appropriate human cell models for study. This review discusses the impact of two complementary, state-of-the-art technologies on T2D genetic research: the generation of stem cell-derived, endocrine pancreas-lineage cells and the editing of their genomes...
2016: F1000Research
https://www.readbyqxmd.com/read/27500307/hypoxic-preconditioning-improves-the-therapeutic-potential-of-aging-bone-marrow-mesenchymal-stem-cells-in-streptozotocin-induced-type-1-diabetic-mice
#16
Muhammad Waseem, Irfan Khan, Hana'a Iqbal, Sana Eijaz, Shumaila Usman, Nazia Ahmed, Gulzar Alam, Asmat Salim
Insulin replacement is the current therapeutic option for type-1 diabetes. However, exogenous insulin cannot precisely represent the normal pattern of insulin secretion. Another therapeutic strategy is transplantation of pancreatic islets, but this is limited by immune rejection, intrinsic complications, and lack of donor availability. Stem cell therapy that results in the regeneration of insulin-producing cells represents an attractive choice. However, with advancing age, stem cells also undergo senescence, which leads to changes in the function of various cellular processes that result in a decrease in the regeneration potential of these aging stem cells...
October 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27473069/the-quest-to-make-fully-functional-human-pancreatic-beta-cells-from-embryonic-stem-cells-climbing-a-mountain-in-the-clouds
#17
REVIEW
James D Johnson
The production of fully functional insulin-secreting cells to treat diabetes is a major goal of regenerative medicine. In this article, I review progress towards this goal over the last 15 years from the perspective of a beta cell biologist. I describe the current state-of-the-art, and speculate on the general approaches that will be required to identify and achieve our ultimate goal of producing functional beta cells. The need for deeper phenotyping of heterogeneous cultures of stem cell derived islet-like cells in parallel with a better understanding of the heterogeneity of the target cell type(s) is emphasised...
October 2016: Diabetologia
https://www.readbyqxmd.com/read/27426087/umbilical-cord-derived-mesenchymal-stem-cells-useful-in-insulin-production-another-opportunity-in-cell-therapy
#18
Shabari Sarang, Chandra Viswanathan
BACKGROUND AND OBJECTIVES: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. METHODS AND RESULTS: We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors...
May 30, 2016: International Journal of Stem Cells
https://www.readbyqxmd.com/read/27400873/cell-therapies-for-pancreatic-beta-cell-replenishment
#19
REVIEW
Bernard Okere, Laura Lucaccioni, Massimo Dominici, Lorenzo Iughetti
The current treatment approach for type 1 diabetes is based on daily insulin injections, combined with blood glucose monitoring. However, administration of exogenous insulin fails to mimic the physiological activity of the islet, therefore diabetes often progresses with the development of serious complications such as kidney failure, retinopathy and vascular disease. Whole pancreas transplantation is associated with risks of major invasive surgery along with side effects of immunosuppressive therapy to avoid organ rejection...
July 11, 2016: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/27363412/stem-cell-based-therapies-for-improving-islet-transplantation-outcomes-in-type-1-diabetes
#20
Joao Paulo Monteiro Carvalho Mori Cunha, Conny Gysemans, Pieter Gillard, Chantal Mathieu
Beta-cell replacement by human islets or whole pancreas offers a life-saving therapeutic remedy for patients suffering from type 1 diabetes, providing considerable advantages with respect to diminishing total daily insulin dose and lowering frequencies of debilitating hypoglycemic reactions as well as preventing chronic micro- and macrovascular complications. Although remarkable progress has been made in this area, several hurdles remain, hampering its wide-spread applicability. Such hurdles include a limiting supply of islets, the necessity of several donors to achieve enough islet mass for insulin independence, and graft failure because of metabolic pressure, continued autoimmunity, alloimmunity, high concentrations of immunosuppressive drugs as well as oxidative stress caused by hypoxia or inflammation...
June 28, 2016: Current Diabetes Reviews
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