Volume 15.42 | Oct 27

Issue 15.42 October 27, 2014
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TOP STORY
Lab-Developed Intestinal Organoids Form Mature Human Tissue in Mice
Researchers have successfully transplanted “organoids” of functioning human intestinal tissue grown from pluripotent stem cells in a lab dish into mice – creating an unprecedented model for studying diseases of the intestine. [Press release from Cincinnati Children’s discussing online prepublication in Nature Medicine]
Press Release | Abstract | Video
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PUBLICATIONS (Ranked by impact factor of the journal)
Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways
Upon heterotypic interaction, exosomes were transferred from stromal to BrCa cells. RNA within exosomes, which are largely noncoding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent antiviral signaling. [Cell] Abstract | Graphical Abstract

Engineering Toxin-Resistant Therapeutic Stem Cells to Treat Brain Tumors
Stem cell-based delivery of IL13-pseudomonas exotoxin (PE) in a clinically-relevant glioblastoma (GBM) resection model led to increased long-term survival of mice compared to IL13-PE protein infusion. Moreover, multiple patient-derived GBM lines responded to treatment, underscoring its clinical relevance. [Stem Cells]
Abstract | Press Release

Ibrutinib Interferes with the Cell-Mediated Anti-Tumor Activities of Therapeutic CD20 Antibodies: Implications for Combination Therapy
Novel Bruton Tyrosine Kinase inhibitor ibrutinib and Phosphatidyl-4-5-biphosphate 3-Kinase-δ inhibitor idelalisib are promising drugs for chronic lymphocytic leukemia and B-non Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. Scientists investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both Type I and Type II CD20 antibodies. [Haematologica] Abstract | Full Article

Adoptive Immunotherapy of Epithelial Ovarian Cancer with Vγ9Vδ2 T Cells, Potentiated by Liposomal Alendronic Acid
When injected into the peritoneal cavity, free and liposomal alendronic acid were both highly effective as sensitizing agents, enabling infused γδ T cells to promote the regression of established ovarian tumors by over one order of magnitude. [J Immunol] Abstract

miR-21 Improves the Neurological Outcome after Traumatic Brain Injury in Rats
Researchers evaluated the impact of microRNA (miR)-21 on apoptosis and angiogenesis in brain after traumatic brain injury. They found that miR-21 inhibited apoptosis and promoted angiogenesis through regulating the expression of apoptosis- and angiogenesis-related molecules. [Sci Rep] Full Article

Human iPS Cell-Engineered Cardiac Tissue Sheets with Cardiomyocytes and Vascular Cells for Cardiac Regeneration
Human induced pluripotent stem cells (HiPSC)-cardiac tissue sheets transplantation to rat infarcted hearts significantly improved cardiac function. In addition to neovascularization, scientists confirmed that engrafted human cells mainly consisted of cardiomyocytes in >40% of transplanted rats four weeks after transplantation. [Sci Rep] Full Article

Sustained Inhibition of Hepatitis B Virus Replication In Vivo Using RNAi-Activating Lentiviruses
Investigators report on the propagation of lentiviral vectors that successfully deliver hepatitis B virus-targeting RNA interference (RNAi) activators to liver cells. [Gene Ther] Abstract

CXCL10-Induced Migration of Adoptively Transferred Human Natural Killer Cells toward Solid Tumors Causes Regression of Tumor Growth In Vivo
Scientists show that ex vivo expansion of human natural killer (NK) cells results in a tenfold increased expression of the chemokine receptor chemokine (C-X-C motif) receptor compared with resting NK cells. Consequently, these NK cells displayed an improved migratory capacity toward solid tumors, which was dependent on tumor-derived C-X-C motif ligand 10 (CXCL10). [Cancer Immunol Immunother] Abstract

Functional Regeneration of Supraspinal Connections in a Patient with Transected Spinal Cord following Transplantation of Bulbar Olfactory Ensheathing Cells with Peripheral Nerve Bridging
A 38-year-old man sustained traumatic transection of the thoracic spinal cord at upper vertebral level Th9. One of the patient’s olfactory bulbs was removed and used to derive a culture containing olfactory ensheathing cells and olfactory nerve fibroblasts. Following resection of the glial scar the cultured cells were transplanted into the spinal cord stumps above and below the injury, and the 8 mm gap bridged by four strips of autologous sural nerve. [Cell Transplant] Full Article | Press Release

Melatonin Pretreatment Improves the Survival and Function of Transplanted Mesenchymal Stem Cells after Focal Cerebral Ischemia
Scientists examined the effect of melatonin pretreatment on mesenchymal stem cells (MSCs) under ischemia-related conditions in vitro and after transplantation into ischemic rat brain. They show that melatonin pretreatment greatly increased survival of MSCs in vitro and reduced their apoptosis after transplantation into ischemic brain. [Cell Transplant] Full Article

View Data: UM729, a Novel Small Molecule for Ex Vivo Expansion of Human hSCs
 
REVIEWS
Synthetic Lethality and Cancer Therapy: Lessons Learned from the Development of PARP Inhibitors
The authors discuss the biological rationale for BRCA-poly(ADP-ribose) polymerase (PARP) synthetic lethality, how the synthetic lethal approach is being assessed in the clinic, and how mechanisms of resistance are starting to be dissected. Applying the synthetic lethal concept to target non-BRCA-mutant cancers also has clear potential, and they discuss how some of the principles learned in developing PARP inhibitors might also drive the development of additional genetic approaches. [Annu Rev Med] Abstract

Optimizing Drug Therapy in Pediatric SCT: Focus on Pharmacokinetics
The authors summarize the pharmacokinetic/dynamic data of hematopoietic SCT conditioning and post-grafting immunosuppression presented at the First Annual Pediatric Bone Marrow Transplant Consortium (PBMTC) meeting in April 2013. [Bone Marrow Transplant] Abstract

The Potential Role for Regulatory T-Cell Therapy in Vascularized Composite Allograft Transplantation
Vascularized composite allograft (VCA) transplantation restores defects to a degree not possible by conventional techniques. The authors consider the evidence for regulatory T cells therapy in VCA transplantation. [Curr Opin Organ Transplant] Abstract

Visit our reviews page to see a complete list of reviews in the cell, gene and immunotherapy research field.

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SCIENCE NEWS
Aduro Presents Updated Interim Results from Phase Ib Clinical Trial in Mesothelioma
Aduro BioTech, Inc. announced the presentation of updated safety and efficacy data from an ongoing Phase Ib clinical trial of its novel immunotherapy CRS-207 in combination with standard chemotherapy in patients with unresectable malignant pleural mesothelioma. [Press release from Aduro Biotech (Business Wire) discussing research presented at the 12th International Mesothelioma Interest Group (iMig) Conference, Cape Town]
Press Release

Verastem Presents New Data on Mesothelioma Programs
Verastem, Inc., focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, announced the presentation of clinical and preclinical data in oral presentation and discussion sessions. [Press release from Verastem, Inc. discussing research presented at the 12th International Mesothelioma Interest Group (iMig) Conference, Cape Town] Press Release

Phase II Data in Crohn’s Disease for Celgene’s Oral Antisense Therapy GED-0301 to Be Presented
Celgene International Sàrl announced that results from a double-blind, placebo-controlled, multicenter Phase II trial of GED-0301 in 166 patients with active Crohn’s disease will be presented. [Press release from Celgene International Sàrl discussing research presented at the United European Gastroenterology (UEG) Week, Vienna] Press Release | Abstract

Global Controls in Stem Cells
 
POLICY
Managers of Discredited STAP Stem Cell Study Refund Salary
The top administrators of RIKEN, Japan’s national network of research laboratories, will voluntarily return one to three months of their salaries to atone for their responsibility for the STAP stem cell fiasco. [ScienceInsider] Editorial

Overhaul of Chinese Science Spending Looms
The Chinese government is readying a major shake-up of how it doles out science funding. The Ministry of Science and Technology may hand control of the lion’s share of research spending to as-yet-unidentified “independent institutes”. [ScienceInsider] Editorial

As Spending Cuts Loom, Embattled Italian Scientists Plea for Mercy
Steep budget cuts could push Italian universities and research centers beyond the point of no return, an academic body warned. [ScienceInsider] Editorial

Indian Research Scholars Welcome Big Bonanza in Stipends
An announcement from the Indian government that young scientists will receive a roughly 60% increase in their stipends drew a mixed reaction from the scientific community. [ScienceInsider] Editorial

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BUSINESS
Celltex Announces ‘Joint’ Partnership with Arthritis Foundation South Central Region
Celltex Therapeutics Corporation announced a partnership with the Arthritis Foundation South Central Region. The coming together of these organizations marks a milestone for the future of regenerative medicine for people who are living with arthritis. [Celltex Therapeutics] Press Release

UC San Diego Named Stem Cell “Alpha Clinic”
In a push to further speed clinical development of emerging stem cell therapies, Sanford Stem Cell Clinical Center at UC San Diego Health System was named one of three new “alpha clinics” by the California Institute for Regenerative Medicine. [UC San Diego Health System] Press Release

The New York Stem Cell Foundation Research Institute Announces Largest-Ever Stem Cell Repository
The New York Stem Cell Foundation Research Institute, through the launch of its repository in 2015, will provide for the first time the largest-ever number of stem cell lines available to the scientific research community. Initially, over 600 induced pluripotent stem cell lines and 1,000 cultured fibroblasts from over 1,000 unique human subjects will be made available, with an increasing number available in the first year. [The New York Stem Cell Foundation] Press Release

AgonOx’s OX40 Platform Being Utilized in MedImmune’s Phase I OX40 Agonist Study
AgonOx, a biotechnology company focused on immunotherapy development, announced that its OX40 platform is being utilized in MedImmune’s Phase I trial of its humanized OX40 agonist, MEDI6383. [AgonOx] Press Release

Clinical Trial to Evaluate Two Biothera Cancer Drugs for Advanced Pancreatic Cancer
A Phase Ib clinical trial at the University of Illinois at Chicago will evaluate a new combination therapy for advanced pancreatic cancer that includes two Biothera cancer immunotherapy drug candidates. [Biothera]
Press Release

TapImmune Provides Update on PolyStart™ Vaccine Platform Applicable to Cancer and Infectious Disease
TapImmune, Inc. provided an update on the status of its PolyStart™ vaccine technology platform in light of recent global concerns regarding pandemic infections and emerging viral threats such as Ebola and Enterovirus. [TapImmune, Inc.] Press Release

First Patient Successfully Implanted in Safety/Efficacy Study of Beta-O2’s ßAir Bio-Artificial Pancreas for Type 1 Diabetes
Beta-O2 announced that the first patient participating in the company’s first broad study of the ßAir Bio-Artificial Pancreas has been successfully implanted. [Beta-O2 Technologies Ltd.] Press Release

Nuvo Research® Completes WF10™ U.S. Market Study for Treatment of Refractory Allergies
Nuvo Research Inc. announced the results of a market study commissioned to investigate the U.S. opportunity for the company’s experimental immunotherapy product, WF10, as a treatment for patients with refractory allergic rhinitis. [Nuvo Research Inc.] Press Release

Pluristem Advances Its Second Major Cell Therapy Product Line from Development to Large-Scale Manufacturing
Pluristem Therapeutics Inc. announced that it has completed development of its second major product line, and can now begin manufacturing the cells on a large-scale at its state-of-the art facility in order to meet demand for anticipated studies in a range of hematologic conditions. [Pluristem Therapeutics Inc.] Press Release
 
NIH
Center for Scientific Review; Notice of Closed Meetings (FR Doc. No: 2014-25039)

Center for Scientific Review; Notice of Closed Meetings (FR Doc. No: 2014-25037)

National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting (FR Doc. No: 2014-25042)

National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting (FR Doc. No: 2014-25041)
 
EVENTS
NEW 20th Association for Molecular Pathology (AMP) Annual Meeting
November 12-15, 2014
National Harbor, United States

Visit our events page to see a complete list of events in the cell, gene and immunotherapy community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Collaborative Training Program in Musculoskeletal Health Research (Western University)

Postdoctoral Position – Muscle Cell Therapy (I-Stem)

Graduate Student – Pediatric Cancers (University of Calgary)

Research Assistant – Cell Therapy (Institute of Biochemistry of the Romanian Academy)

Postdoctoral Position – Leukemic Stem Cells (BC Cancer Agency)

Postdoctoral Position – Hepatic Regenerative Medicine (INSERM)

Postdoctoral Fellowship – AAV Gene Therapy (Icahn School of Medicine at Mount Sinai)

Postdoctoral Position – Novel Mediators of Cardiovascular Disease and Novel Therapeutic Strategies (Monzino Cardiology Center)

Postdoctoral Position – Transplantation Aspects of Hepatocytes Derived from Human Pluripotent Stem Cells (INSERM UMR 1064)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Liver Cell Biology (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)


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