293 results match your criteria: "Rangos Research Center[Affiliation]"

High-purity enrichment of functional cardiovascular cells from human iPS cells.

Cardiovasc Res

August 2012

Department of Developmental Biology, University of Pittsburgh School of Medicine, 530 45th Street, Rangos Research Center, Pittsburgh, PA 15201, USA.

Aims: A variety of human inherited heart diseases affect the normal functions of cardiomyocytes (CMs), endothelial cells (ECs), or smooth muscle cells (SMCs). To study human heart disease and generate cardiac cells for basic and translational research, an efficient strategy is needed for production of cardiac lineages from human stem cells. In the present study, a highly reproducible method was developed that can simultaneously enrich a large number of CMs and cardiac SMCs and ECs from human induced pluripotent stem (iPS) cells with high purity.

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Isolation of human islets for autologous islet transplantation in children and adolescents with chronic pancreatitis.

J Transplant

August 2012

Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.

Chronic pancreatitis is an inflammatory disease of the pancreas that causes permanent changes in the function and structure of the pancreas. It is most commonly a complication of cystic fibrosis or due to a genetic predisposition. Chronic pancreatitis generally presents symptomatically as recurrent abdominal pain, which becomes persistent over time.

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ICA69 (islet cell autoantigen 69 kDa) is a protein implicated in type 1 diabetes mellitus in both the non-obese diabetic (NOD) mouse model and humans. ICA69 is encoded by the Ica1 gene on mouse chromosome 6 A1-A2. We previously reported reduced ICA69 expression in the thymus of NOD mice compared with thymus of several non-diabetic mouse strains.

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MicroRNAs (miRNAs) are a group of small, noncoding RNAs that act as novel regulators of gene expression through the post-transcriptional repression of their target mRNAs. miRNAs have been implicated in diverse biologic processes, and it is estimated that up to half of all transcripts are regulated by miRNAs. Recent studies also demonstrate a critical role for miRNAs in renal development, physiology, and pathophysiology.

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Conditional deletion of fibroblast growth factor receptors (Fgfrs) 1 and 2 in the metanephric mesenchyme (MM) of mice leads to a virtual absence of MM and unbranched ureteric buds that are occasionally duplex. Deletion of Fgfr2 in the MM leads to kidneys with cranially displaced ureteric buds along the Wolffian duct or duplex ureters. Mice with point mutations in Fgfr2's binding site for the docking protein Frs2α (Fgfr2(LR/LR)), however, have normal kidneys; the roles of the Fgfr2/Frs2α signaling axis in MM development and regulating the ureteric bud induction site are incompletely understood.

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Chlamydia trachomatis infection control programs: lessons learned and implications for vaccine development.

Infect Dis Obstet Gynecol

January 2012

Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Room 9123, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.

Chlamydia trachomatis control efforts that enhance detection and treatment of infected women may paradoxically increase susceptibility of the population to infection. Conversely, these surveillance programs lower incidences of adverse sequelae elicited by genital tract infection (e.g.

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Uses of cardiomyocytes generated from induced pluripotent stem cells.

Stem Cell Res Ther

November 2011

Department of Developmental Biology, University of Pittsburgh, Rangos Research Center, Pittsburgh, PA 15201, USA.

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C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937 monocytes in condition of hyperglycemia.

Inflamm Res

January 2012

Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

Objective: We investigated C-peptide effects on inflammatory cytokine release and adhesion of monocytes exposed to high glucose and lipopolysaccharide (LPS) in vitro.

Materials And Methods: Monocytic cells (U-937) were cultured in the presence of 30 mmol/L glucose and stimulated with 0.5 ng/μL LPS in the presence or absence of C-peptide (1 μmol/L) for 24 h to induce inflammatory cytokine secretion.

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Pig-to-nonhuman primates pancreatic islet xenotransplantation: an overview.

Curr Diab Rep

October 2011

Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.

The therapy of type 1 diabetes is an open challenging problem. The restoration of normoglycemia and insulin independence in immunosuppressed type 1 diabetic recipients of islet allotransplantation has shown the potential of a cell-based diabetes therapy. Even if successful, this approach poses a problem of scarce tissue supply.

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Aims/hypothesis: Reactive oxygen species (ROS) generated during hyperglycaemia are implicated in the development of diabetic vascular complications. High glucose increases oxidative stress in endothelial cells and induces apoptosis. A major source of ROS in endothelial cells exposed to glucose is the NAD(P)H oxidase enzyme.

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Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice.

Gastroenterology

October 2011

Department of Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania 15224, USA.

Background & Aims: There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response.

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Role of fibroblast growth factor receptor signaling in kidney development.

Am J Physiol Renal Physiol

August 2011

Rangos Research Center, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Fibroblast growth factor receptors (Fgfrs) consist of four signaling family members and one nonsignaling "decoy" receptor, Fgfr-like 1 (Fgfrl1), all of which are expressed in the developing kidney. Several studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB) in cultured tissues. Transgenic and conditional knockout approaches in whole animals have shown that Fgfr1 and Fgfr2 (predominantly the IIIc isoform) in kidney mesenchyme are critical for early MM and UB formation.

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Amnion-derived stem cells: in quest of clinical applications.

Stem Cell Res Ther

May 2011

Department of Developmental Biology, University of Pittsburgh, 530 45th Street, 8112 Rangos Research Center, Pittsburgh, PA 15201, USA.

In the promising field of regenerative medicine, human perinatal stem cells are of great interest as potential stem cells with clinical applications. Perinatal stem cells could be isolated from normally discarded human placentae, which are an ideal cell source in terms of availability, the fewer number of ethical concerns, less DNA damage, and so on. Numerous studies have demonstrated that some of the placenta-derived cells possess stem cell characteristics like pluripotent differentiation ability, particularly in amniotic epithelial (AE) cells.

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Targeting FoxO1 for hypertriglyceridemia.

Curr Drug Targets

August 2011

Division of Immunogenetics, Rangos Research Center, Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

Hypertriglyceridemia is characterized by increased production and decreased clearance of triglyceride-rich lipoproteins including very low-density lipoprotein (VLDL) and chylomicron. Due to its proatherogenic profile, hypertriglyceridemia contributes to the development of atherosclerosis and coronary artery disease. While the pathophysiology of hypertriglyceridemia remains poorly understood, its close association with obesity and type 2 diabetes implicates insulin resistance in the pathogenesis of hypertriglyceridemia.

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Mice with conditional deletion of fibroblast growth factor receptor 2 (Fgfr2) in the ureteric bud using a Hoxb7cre line (Fgfr2(UB-/-)) develop severe ureteric branching defects; however, ureteric deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key docking protein that transmits fibroblast growth factor receptor intracellular signaling (Frs2α(UB-/-)) leads to mild ureteric defects. Mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2(LR/LR)) have normal kidneys. The aim of this study was to determine the relationship between Fgfr2 and Frs2α in the ureteric lineage.

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Vesicoureteral reflux (VUR) is a common pediatric anomaly linked to renal scarring and hypertension. Although there are many mouse VUR models, cystograms have previously only been performed in euthanized animals, thus preventing serial assessments for VUR in the same animal and not delineating "live" physiology. Our purpose was to develop a live murine cystogram assay that could be used serially to track reflux.

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From fibroblast cells to cardiomyocytes: direct lineage reprogramming.

Stem Cell Res Ther

January 2011

Department of Developmental Biology, University of Pittsburgh, 530 45th Street, 8117 Rangos Research Center, Pittsburgh, PA 15201, USA.

Recent advances in stem cell biology have established the feasibility of reprogramming human and murine fibroblast cells into induced pluripotent stem cells. Three master regulators have been demonstrated to be sufficient in the management of cell status of 'pluripotent' versus 'differentiated'. The same strategy has been used to directly convert one somatic cell type into another cell type, such as the converting of exocrine pancreas cells into cells closely resembling beta cells and the reprogramming of fibroblast cells into functional neuron cells.

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Fibroblast growth factor receptors (Fgfrs) are expressed throughout the developing kidney. Several early studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB). Transgenic mice that over-express a dominant negative receptor isoform develop renal aplasia/severe dysplasia, confirming the importance of Fgfrs in renal development.

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C-peptide and long-term complications of diabetes.

Pediatr Diabetes

May 2011

Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.

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Fibroblast growth factor receptors (Fgfrs) have critical roles in kidney development. FgfrIIIb is thought to act in epithelium, while FgfrIIIc functions in mesenchyme. We aimed to determine roles of Fgfr2IIIc in kidney development.

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Meckel-Gruber syndrome (MKS) is a recessive disorder resulting in multiple birth defects that are associated with mutations affecting ciliogenesis. We recovered a mouse mutant with a mutation in the Mks1 gene (Mks1(del64-323)) that caused a 260-amino-acid deletion spanning nine amino acids in the B9 domain, a protein motif with unknown function conserved in two other basal body proteins. We showed that, in wild-type cells, Mks1 was localized to the mother centriole from which the cilium was generated.

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Drug delivery technologies for autoimmune disease.

Expert Opin Drug Deliv

November 2010

University of Pittsburgh School of Medicine, Diabetes Institute, Department of Pathology, Rangos Research Center 6123, Pittsburgh, PA 15224, USA.

Importance Of The Field: Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome.

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Impaired pancreatic development in Hif2-alpha deficient mice.

Biochem Biophys Res Commun

August 2010

Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, One Children's Drive, 4401 Penn Avenue, Rangos Research Center, Pittsburgh, PA 15244, United States.

Accumulating data suggest the existence of a link between hypoxia and maintenance of the undifferentiated cell state, but little is known about the cellular signaling mechanisms underlying this process. Recent reports reveal a direct link between components of the hypoxia signaling pathway and Notch pathway in maintaining precursor cells in an undifferentiated state. Here, we report that in the developing mouse pancreas, Hif2-alpha is expressed in pancreatic progenitor cells, but its expression is lost in committed endocrine progenitors as well as in differentiated endocrine and exocrine cells.

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Gene-environment interaction in type 1 diabetes mellitus.

Endocrinol Nutr

December 2009

Division of Immunogenetics, Children's Hospital of Pittsburgh, Rangos Research Center, Pittsburgh, PA, USA.

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