Cell Therapy News Volume 17.42 | Nov 21 2016

TOP STORY

In Vivo Genome Editing via CRISPR/Cas9 Mediated Homology-Independent Targeted Integration

Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9), technology, the authors devised a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo. As a proof of concept of its therapeutic potential, they demonstrated the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Engineered Human Pluripotent-Stem-Cell-Derived Intestinal Tissues with a Functional Enteric Nervous System

Scientists recapitulated normal intestinal enteric nervous system development by combining human-pluripotent stem cells-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. [Nat Med] Abstract | Press Release

Improved Vascularization of Porous Scaffolds through Growth Factor Delivery from Heparinized Polyethylene Glycol Hydrogels

In order to determine its efficacy with sustained release, heparin was covalently incorporated into degradable and non-degradable polyethylene glycol hydrogels. After in vitro characterization of their physicochemical properties, growth factor loaded, heparinized Type D gels were formed within the pores of porous polyurethane disks, which were then implanted and evaluated in a subcutaneous model. [Acta Biomater] Abstract

miR-101 Targets the EZH2/Wnt/β-Catenin the Pathway to Promote the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

Investigators found that the miR-101 expression level was significantly increased during the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. miR-101 depletion suppressed osteogenic differentiation, whereas the overexpression of miR-101 was sufficient to promote this process. They further demonstrated that enhancer of zeste homolog 2 (EZH2) was a target gene of miR-101. miR-101 also promoted in vivo bone formation by hBMSCs. [Sci Rep] Full Article

Human Endometrial Mesenchymal Stem Cells Exhibit Intrinsic Anti-Tumor Properties on Human Epithelial Ovarian Cancer Cells

Whether endometrial mesenchymal stem cells (EnSCs) endow innate anti-tumor properties on epithelial ovarian cancer (EOC) cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, the authors found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. [Sci Rep] Full Article

The Novel miR-9600 Suppresses Tumor Progression and Promotes Paclitaxel Sensitivity in Non–Small-Cell Lung Cancer through Altering STAT3 Expression

miR-9600 inhibited cell growth, hampered expression of cell cycle-related proteins and inhibited cell migration and invasion in human non–small-cell lung cancer cell lines. Further, miR-9600 significantly suppressed tumor growth in nude mice. [Mol Ther Nucleic Acids] Full Article

A Reproducible Method for the Isolation and Expansion of Ovine Mesenchymal Stromal Cells from Bone Marrow for Use in Regenerative Medicine Preclinical Studies

Scientists described a method for isolation and expansion of fibroblastic-like, adherent ovine mesenchymal stromal cells (MSCs) that express CD44, CD90, CD140a, CD105 and CD166, and display trilineage differentiation potential. The osteogenic potential of MSCs derived following this methodology was further evaluated in vivo in a translational model of osteonecrosis of the femoral head, in which the persistence of grafted cells in the host tissue and their lineage commitment into osteoblasts and osteocytes was demonstrated by tracking enhanced green fluorescent protein-labelled cells. [J Tissue Eng Regen Med] Abstract

Absence of Spontaneous Response Improvement Beyond Day +100 after Autologous Stem Cell Transplantation in Multiple Myeloma

Researchers evaluated the rate of improved response and outcome beyond day +100 after autologous stem-cell transplantation (ASCT), with and without maintenance therapy. One hundred and forty-four patients who underwent single ASCT with chemosensitive disease and achieved less than CR at day 100 post ASCT were evaluated. [Bone Marrow Transplant] Abstract

Immunological Quality and Performance of Tumor Vessel-Targeting CAR-T Cells Prepared by mRNA-EP for Clinical Research

Scientists prepared anti-vascular endothelial growth factor receptor 2 (VEGFR2) CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6–12 hours after mRNA-EP. Triple transfer of murine anti-VEGFR2 CAR-T cells into B16BL6 tumor-bearing mice demonstrated an antitumor effect comparable to that for the single transfer of CAR-T cells engineered with retroviral vector. [Mol Ther Oncolytics] Full Article

AAV-Mediated Sirt1 Overexpression in Skeletal Muscle Activates Oxidative Capacity but Does Not Prevent Insulin Resistance

Researchers examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1) specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice. AAV1-Sirt1-treated mice showed up-regulated expression of key genes related to β-oxidation together with increased levels of phosphorylated AMP protein kinase. [Mol Ther Methods Clin Dev] Full Article

CRISPR-Cas9 System as a Versatile Tool for Genome Engineering in Human Cells

The authors discuss the most recent advancements in the molecular basis of the type II CRISPR/Cas system and encapsulate applications and elements affecting its use in human cells. They also propose possible applications covering its uses ranging from basic science to implementation in the clinic. [Mol Ther Nucleic Acids] Full Article

Molecular Imaging and Cancer Gene Therapy

The authors discuss most recent advances in cancer gene therapy and molecular approaches as well as imaging techniques that are utilized to detect cancer gene therapeutics and to monitor the patients’ response to these therapies worldwide, particularly in Iranian Academic Medical Centers and Hospitals. [Cancer Gene Ther] Abstract

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

ImmunoCellular Therapeutics Reports Updated Immune Monitoring Data from ICT-107 Phase II Trial in Newly Diagnosed Glioblastoma

ImmunoCellular Therapeutics, Ltd. announced the presentation of updated immune monitoring data from the Phase II trial of ICT-107 in patients with newly diagnosed glioblastoma. Also presented were updated long-term survival data from the Phase I trial of ICT-107. ICT-107 is a dendritic cell-based immunotherapy targeting multiple tumor-associated antigens on glioblastoma stem cells. [Press release from ImmunoCellular Therapeutics, Ltd. discussing research presented at the Society for Neuro-Oncology Annual Meeting 2016, Scottsdale] Press Release

New Data from Global aHUS Registry Show a Three-Fold Reduction in Post-Transplant Dialysis in Patients Initiating Soliris^® (Eculizumab) Treatment Prior to Transplant Compared to Initiating Treatment Post-Transplant

Alexion Pharmaceuticals, Inc. announced that researchers presented new data from an analysis of patients enrolled in the Global atypical Hemolytic Uremic Syndrome (aHUS) Registry, demonstrating that initiation of Soliris^® prior to kidney transplant reduces the risk of dialysis post-transplant in patients with aHUS. Specifically, results showed that starting Soliris prior to transplant reduced the likelihood of dialysis three-fold compared to initiating Soliris post-transplant. [Press release from Alexion Pharmaceuticals, Inc. discussing research presented at the 2016 Annual Meeting of the American Society of Nephrology (ASN), Chicago] Press Release

Salk Institute Awarded $25 Million Grant from Helmsley Charitable Trust

The Salk Institute for Biological Studies has received a $25 million grant—a renewal of the largest research gift in the Institute’s 56-year history—that will be used to continue exploring an ambitious range of projects aimed at understanding the role chronic inflammation plays in driving human disease. [Salk Institute for Biological Studies] Press Release

Morgridge–UW Project Investigates Tissue-Engineered Arteries for Transplant

The prospect of creating artery “banks” available for cardiovascular surgery, bypassing the need to harvest vessels from the patient, could transform treatment of many common heart and vascular ailments. The Morgridge Institute for Research and the University of Wisconsin–Madison will address both the engineering and biomedical hurdles in this process through a five year, $8 million project funded by the National Heart, Lung, and Blood Institute. [University of Wisconsin–Madison (UW)] Press Release

OrbusNeich Introduces a New Generation COMBO Plus Dual Therapy Stent for Active Healing

OrbusNeich has announced the launch of its latest generation Dual Therapy Stent, the COMBO Plus. The COMBO Plus has a unique anti-CD34 antibody biological coating that offers an advanced approach to active vessel healing combined with improved deliverability for patients with complex coronary artery disease. Following implantation, the biological coating on the outer surface of the COMBO Plus immediately captures endothelial progenitor cells and initiates the formation of an endothelial layer. [OrbusNeich] Press Release

Pharnext Announces that the Data Safety Monitoring Board Recommends Continuing the Ongoing Phase III Trial of PXT3003 for Charcot-Marie-Tooth Disease Type 1A

Pharnext SA announced that the independent Data Safety Monitoring Board (DSMB) has completed its first pre-specified safety evaluation of PXT3003 in the ongoing PLEO-CMT Phase III clinical trial. Based on a review of safety data from 100 patients who completed at least three months of study treatment, the DSMB recommended continuing the PLEO-CMT study as planned. [Pharnext SA (Business Wire, Inc.)] Press Release

Celyad Announces the Approval to Initiate Its NKR-2 CAR-T Clinical Trial in Belgium

Celyad announced the approval in Belgium to initiate the THerapeutic Immunotherapy with NKR-2 (THINK) clinical trial. THINK is the second clinical trial of its NKR-2 product candidate, a CAR-T cell therapy using NKG2D ligands as a target, to evaluate safety and efficacy in seven cancer indications including both solid and hematological malignancies. [Celyad] Press Release

Center for Regenerative Medicine Receives Three Prestigious NIH Awards To Further Stem Cell Research

The Center for Regenerative Medicine at Boston Medical Center and Boston University School of Medicine has received three prestigious awards from the National Institutes of Health to further its commitment to induced pluripotent stem cell research and education. [Boston University School of Medicine] Press Release

Vertera Spine’s COHERE Fusion Device Wins Award for Best Spine Technologies for 2016

Vertera Spine announced that the COHERE^® Cervical Interbody Fusion Device has been recognized by Orthopedics This Week as one of the Top Ten Best Spine Technologies for 2016. COHERE features Vertera Spine’s patented porous PEEK (polyetheretherketone) Scoria^® biomaterial technology, a porous architecture that seamlessly integrates with solid PEEK to mimic the cancellous to cortical transition of native bone. [Vertera Spine (PR Newswire Association LLC.)] Press Release

Agilis Biotherapeutics Achieves FDA “Rare Pediatric Disease” Designation for AADC Gene Therapy Candidate

Agilis Biotherapeutics, LLC (Agilis) announced that the Food and Drug Administration (FDA) has granted a Rare Pediatric Disease (RPD) designation for its gene therapy product candidate, AGILAADC for the treatment of Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency. The RPD designation supplements the Orphan Drug Designation granted by the FDA and announced by Agilis earlier this year. [Agilis Biotherapeutics, LLC] Press Release

Regenicin Signs Supplier Agreement with Pure Med Farma LLC to Provide Closed Herd Collagen for the Manufacturing of NovaDerm^®

Regenicin, Inc. announced that they have signed a supplier agreement with Pure Med Farma, LLC to provide closed herd collagen for the production of its proprietary collagen scaffolds for the manufacturing of NovaDerm^®. [Regenicin, Inc.] Press Release

Cautious Welcome for UK’s Vague £2 Billion Research Pledge

UK scientists have welcomed a surprise government promise to invest an extra £2 billion (US$2.5 billion) per year into research and development by 2020 – although details of the pledge will not be made clear for at least another two days. [Nature News] Editorial

Conservatives, Liberals Team Up Against Animal Research

“Painful, bizarre, and wasteful experiments.” Buying dogs “just to cut them apart … and kill them.” These statements might sound like the rhetoric used by extreme animal rights groups, but they come from White Coat Waste—a new, unlikely coalition of fiscal conservatives and liberal activists that aims to end federal funding for research involving dogs and other animals by targeting people’s pocketbooks in addition to their heartstrings. [ScienceInsider] Editorial

FDA

Revised Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products Who Have Received Human-Derived Clotting Factor Concentrates; Guidance for Industry; Availability (FR Doc. No:2016-27768) Notice

Withdrawal of Two Proposed Rules (FR Doc. No:2016-27329) Notice

NEW Cellular Therapy 2017 International Symposium
March 16-17, 2017
Erlangen, Germany

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

NEW Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Research Fellow – Fat Tissue-Derived Stem Cells for Treating Metabolic Diseases (SBIC, A*STAR)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

Associate Director – Cellular Process Development (Celgene Corporation)

Postdoctoral Fellowship – Genetic Medicine (Weill Cornell Medical College)

Research Fellow in Pluripotent Stem Cells Self-Renewal Program and Cell Cycle (KU Leuven)

Research Associate – Hematology (Editas Medicine)

Postdoctoral Fellow – Novel Systems for Treatment of Type 1 Diabetes (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Assistant Professor – Developmental Biology (Florida State University)

Postdoctoral Fellow – Pluripotent Stem Cell Technology (University of California Davis)

Postdoctoral Fellow – Oxidative Lung Injury (Temple University)

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