Volume 4.15 | Apr 23

Pancreatic Cell News 4.15 April 23, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs 
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TOP STORY
Pluripotent Stem Cell Models of Shwachman-Diamond Syndrome Reveal a Common Mechanism for Pancreatic and Hematopoietic Dysfunction
Scientists created human pluripotent stem cell models of Shwachman-Diamond syndrome (SDS) through knockdown of Shwachman-Bodian-Diamond syndrome (SBDS) in human embryonic stem cells (hESCs) and generation of induced pluripotent stem cell (iPSC) lines from two patients with SDS. SBDS-deficient hESCs and iPSCs manifest deficits in exocrine pancreatic and hematopoietic differentiation in vitro, enhanced apoptosis, and elevated protease levels in culture supernatants, which could be reversed by restoring SBDS protein expression through transgene rescue or by supplementing culture media with protease inhibitors. [Cell Stem Cell] Abstract

Directed Differentiation of Pluripotent Stem Cells - A Cell Stem Cell Poster
PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

Microphtalmia Transcription Factor (Mitf) Regulates Pancreatic β Cell Function
Scientists showed that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse postnatal development and in the adult islet. A Mitf loss of function mutation results in improved glucose tolerance and enhanced insulin secretion, but no increase in β cell mass in adult mice. [Diabetes] Abstract

Suppression of Epithelial to Mesenchymal Transitioning (EMT) Enhances Ex Vivo Reprogramming of Human Exocrine Pancreatic Tissue towards Functional Insulin Producing β-Like Cells
The aim of this study was to determine whether the human exocrid fraction from the islet isolation procedure could be reprogrammed to provide additional islet tissue for transplantation. The exocrine enriched cells rapidly dedifferentiated in culture and grew as a mesenchymal monolayer. [Diabetes] Abstract

Co-Regulation of Intragenic MicroRNA miR-153 and Its Host Gene Ia-2 β: Identification of miR-153 Target Genes with Functions Related to IA-2β in Pancreas and Brain
Investigators analyzed the genomic organization of miR-153, a microRNA embedded in genes that encode two of the major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2β. They demonstrated that expression of miR-153-2 and Ia-2β in rodents is partially co-regulated as demonstrated by a strong reduction of miR-153 expression levels in Ia-2β knockout and Ia-2/Ia-2β double knockout mice. [Diabetologia
Full Article

Ligand-Bound Thyroid Hormone Receptor Contributes to Reprogramming of Pancreatic Acinar Cells into Insulin-Producing Cells
Investigators used adenovirus vector that expresses ligand-bound thyroid hormone receptor α (TRα) driven by the amylase 2 promoter to induce the reprogramming of pancreatic acinar cells into insulin-producing cells. Treatment with L-3,5,3-triiodothyronine increases the association of TRα with the p85α subunit of PI3K, leading to the phosphorylation and activation of Akt and the expression of Pdx1, Ngn3 and MafA in purified acinar cells. [J Biol Chem] Abstract | Full Article

Pancreatic Tissue Resident Mesenchymal Stromal Cell (MSC)-Like Cells as a Source of In Vitro Islet Neogenesis
Researchers isolated mesenchymal stromal cell – like cells from adult mouse pancreas by collagenase digestion. Upon exposure to islet differentiation serum-free cocktail a significant upregulation of pancreatic markers like Nkx2.2, Nkx6.1, Pdx1, insulin and somatostatin was seen. [J Cell Biochem] Abstract

PANCREATIC CANCER

Nr5a2 Heterozygosity Sensitizes to, and Cooperates with, Inflammation in KRasG12V-Driven Pancreatic Tumourigenesis
Nr5a2+/− and KRasG12V;Ptf1a-Cre;Nr5a2+/− mice were used to investigate whether a full dose of Nr5a2 is required for normal pancreas development, recovery from caerulein-induced pancreatitis, and protection from tumor development. Adult Nr5a2+/− mice did not display histological abnormalities in the pancreas but showed a more severe acute pancreatitis, increased acino-ductal metaplasia and impaired recovery from damage. [Gut]
Abstract

Nontoxic Radioactive Listeriaat Is a Highly Effective Therapy against Metastatic Pancreatic Cancer
Researchers coupled a radioisotope, 188Rhenium, to an attenuated (at) live Listeria monocytogenes (Listeriaat) using Listeria-binding antibodies, thus creating a unique radioactive Listeriaat (RL). They then demonstrated in a highly metastatic pancreatic mouse tumor model that RL delivered radioactivity to the metastases and less abundantly to primary tumors in vivo, without harming normal cells. [Proc Natl Acad Sci USA]
Abstract | Press Release

Transforming Growth Factor-α Activates Pancreatic Stellate Cells and May Be Involved in Matrix Metalloproteinase-1 Upregulation
Scientists evaluated the effects of transforming growth factor-α (TGF-α) on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-α and metalloproteinase-1 in human chronic pancreatitis and pancreatic cancer tissues. TGF-α stimulated the proliferation and migration of PSCs. [Lab Invest] Abstract

Inflammation Increases Cells Expressing ZSCAN4 and Progenitor-Cell Markers in the Adult Pancreas
The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. In the adult human pancreas a small number of ZSCAN4-positive cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. [Am J Physiol-Gastr L] Abstract

Gemcitabine-Loaded Albumin Nanospheres (GEM-ANPs) Inhibit PANC-1 Cells In Vitro and In Vivo
Investigators assessed the drug distribution, side effects, and antitumor activity of GEM-ANPs in vivo. The metabolic viability and flow cytometry analysis revealed that both GEM-ANPs, especially 406-nm GEM-ANPs, could effectively inhibit the metabolism and proliferation and promote the apoptosis of human pancreatic carcinoma (PANC-1) in vitro. [Nanoscale Res Lett] Abstract | Full Article

New TeSR™-E8™ is Here For Feeder-Free Culture of Human ES Cells and iPS Cells

REVIEWS

CD40 Immunotherapy for Pancreatic Cancer
The authors describe both laboratory and clinical efforts to target the CD40 pathway for immunotherapy in pancreatic ductal adenocarcinoma. Findings suggest that CD40 agonists can mediate both T-cell-dependent and T-cell-independent immune mechanisms of tumor regression in mice and patients. [Cancer Immunol Immun] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
INDUSTRY NEWS

Lilly Announces Positive Results of Phase III Trials of Dulaglutide in Type 2 Diabetes
Eli Lilly and Company announced positive top-line results of two additional Phase III AWARD trials for dulaglutide, an investigational, long-acting glucagon-like peptide 1 receptor agonist being studied as a once-weekly treatment for type 2 diabetes. [Eli Lilly and Company] Press Release

Halozyme Initiates Randomized Phase II Trial of PEGPH20 in Pancreatic Cancer
Halozyme Therapeutics, Inc. announced the initiation of a Phase II multicenter, randomized clinical trial evaluating PEGPH20, a proprietary, investigational drug, as a first-line therapy for patients with stage IV metastatic pancreatic cancer. [Halozyme Therapeutics, Inc.] Press Release

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POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW The European Cancer Congress 2013
September 27 – October 1, 2013
Amsterdam, Netherlands

Visit our events page to see a complete list of events in the pancreatic cell community.

JOB OPPORTUNITIES

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

Postdoctoral Fellowship – Developmental Biology/Biophysics (University of Copenhagen)

Scientist/Specialist – Mitochondrial Function (The Nestlé Institute of Health Sciences)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

Postdoctoral Position – Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

Postdoctoral Fellow – Pancreatic Beta Cell Regeneration and Survival (Oklahoma Medical Research Foundation)

Research Associate – Progression and Metastasis of Pancreatic and Breast Cancer (University of North Carolina at Charlotte)


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