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https://www.readbyqxmd.com/read/29319179/muscle-derived-satellite-cells-for-treating-type-1-diabetes-in-rats-rattus-norvegicus
#1
Yu Ren, Hefei Wang, Si Ha, Xingsheng Zhao, Xiao Wang, Yu Lan, Xiaoling Liu
Diabetes mellitus(DM) is a complicated metabolic disease, with the fundamental treatment nowadays being diet control, insulin injections, slet or pancreas transplantation, which is limited because exogenous insulin injections fail to simulate normal insulin secretion in islet beta cells successfully and islet transplantation lacks organ donors. So far, stem cells with highly self-renewal and multi-directional differentiation potential have become a new hope for the treatment of diabetes. In this research, rat Muscle-derived satellite cells *MDSCs*were separated and cultivated in vitro and inducted into insulin-producing cells with observation and identification using dithizone staining and so on...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29288549/transplantation-of-macro-encapsulated-human-islets-within-the-bioartificial-pancreas-%C3%AE-air-to-patients-with-type-1-diabetes-mellitus
#2
Per-Ola Carlsson, Daniel Espes, Amir Sedigh, Avi Rotem, Baruch Zimermann, Helena Grinberg, Tali Goldman, Uriel Barkai, Yuval Avni, Gunilla T Westermark, Lina Carlbom, Håkan Ahlström, Olof Eriksson, Johan Olerud, Olle Korsgren
Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes...
December 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29275427/hope-vs-hype-where-are-we-in-type-1-diabetes
#3
REVIEW
Jay S Skyler
Much progress has been made in type 1 diabetes research. Biological replacement of islet function has been achieved with pancreas transplantation and with islet transplantation. In the future, human embryonic stem cells and/or induced pluripotent stem cells may offer a potentially unlimited source of cells for islet replacement. Another potential strategy is to induce robust beta cell replication so that regeneration of islets can be achieved. Immune interventions are being studied with the hope of arresting the type 1 diabetes disease process to either prevent the disease or help preserve beta cell function...
December 23, 2017: Diabetologia
https://www.readbyqxmd.com/read/29241367/differentiation-of-conjunctiva-mesenchymal-stem-cells-into-secreting-islet-beta-cells-on-plasma-treated-electrospun-nanofibrous-scaffold
#4
Samad Nadri, Ghasem Barati, Hossein Mostafavi, Abdolreza Esmaeilzadeh, Seyed Ehsan Enderami
Transplantation of stem cells using biocompatible nanofibrous scaffolds is a promising therapeutic method for treating Diabetic Mellitus. The aim of this study was to derive insulin-producing cells (IPCs) from conjunctiva-derived mesenchymal stem cell (CJMSCs) and to compare the functionality of differentiated IPCs in a three-dimensional (3D) culture with 2D. Furthermore, the effects of hydrophobicity of scaffold on IPCs differentiation were examined. Scanning electron microscopy (SEM), quantitative real times PCR (qPCR), Immunostaining and flow cytometry were used to analyze fabricated scaffold and the presence of IPCs...
December 14, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29181780/3d-models-of-insulin-producing-%C3%AE-cells-from-primary-islet-cells-to-stem-cell-derived-islets
#5
REVIEW
Diana Ribeiro, Alexander J Kvist, Pernilla Wittung-Stafshede, Ryan Hicks, Anna Forslöw
There is a need for physiologically relevant assay platforms to provide functionally relevant models of diabetes, to accelerate the discovery of new treatment options and boost developments in drug discovery. In this review, we compare several 3D-strategies that have been used to increase the functional relevance of ex vivo human primary pancreatic islets and developments into the generation of stem cell derived pancreatic beta-cells (β-cells). Special attention will be given to recent approaches combining the use of extracellular matrix (ECM) scaffolds with pancreatic molecular memory, which can be used to improve yield and functionality of in vitro stem cell-derived pancreatic models...
November 27, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29150935/generation-of-insulin-producing-cells-from-human-adipose-derived-mesenchymal-stem-cells-on-pva-scaffold-by-optimized-differentiation-protocol
#6
Seyed Ehsan Enderami, Masoud Soleimani, Yousef Mortazavi, Samad Nadri, Ali Salimi
The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The Characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#7
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#8
REVIEW
Yaxi Zhu, Qian Liu, Zhiguang Zhou, Yasuhiro Ikeda
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells...
November 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29083510/on-the-etiology-of-type-1-diabetes-physiological-growth-in-children-impacts-disease-progression
#9
REVIEW
Oskar Skog, Olle Korsgren
The prevailing view is that Type 1 Diabetes (T1D) develops as a consequence of a severe fall in beta-cell mass resulting from T-cell mediated autoimmunity. However, progression from islet autoantibody seroconversion to overt diabetes and finally to total loss of c-peptide production occurs in most affected subjects only slowly over many years or even decades. This slow disease progression should be viewed in relation to the total beta cell mass of only 0.2 - 1.5 g in non-diabetic adults. Focal lesions of acute pancreatitis with accumulation of leukocytes, often located around the ducts, are frequently observed in subjects with recent onset T1D and most patients display extensive periductal fibrosis, the end stage of inflammation...
October 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29058819/involvement-of-dying-beta-cell-originated-messenger-molecules-in-differentiation-of-pancreatic-mesenchymal-stem-cells-under-glucotoxic-and-glucolipotoxic-conditions
#10
Selda Gezginci-Oktayoglu, Evren Onay-Ucar, Serap Sancar-Bas, Ayse Karatug-Kacar, Emine Sekure Nazli Arda, Sehnaz Bolkent
Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type2 diabetes mellitus. Pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized...
October 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#11
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet beta cells. Here we review several approaches to replace beta cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies demonstrating the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28931519/beta-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#12
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
September 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28789815/bioprinting-and-cellular-therapies-for-type-1-diabetes
#13
REVIEW
Dino J Ravnic, Ashley N Leberfinger, Ibrahim T Ozbolat
Type 1 diabetes mellitus is a chronic autoimmune disease that results from the destruction of beta (β) cells in the pancreatic islets, leading to loss of insulin production and resultant hyperglycemia. Recent developments in stem cell biology have generated much excitement for β-cell replacement strategies; β cells are one of many cell types in the complex islet environment and pancreas. In this Opinion, we discuss recent successful attempts to generate β cells and how this can be coupled with bioprinting technologies in order to fabricate pancreas tissues, which holds great potential for type 1 diabetes...
November 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28655312/transplantation-of-human-fetal-pancreatic-progenitor-cells-ameliorates-renal-injury-in-streptozotocin-induced-diabetic-nephropathy
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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