Cell Therapy News Volume 17.45 | Dec 12 2016

TOP STORY

Sinoatrial Node Cardiomyocytes Derived from Human Pluripotent Cells Function as a Biological Pacemaker

The authors describe a transgene-independent method for the generation of sinoatrial node (SAN)-like pacemaker cells (SANLPCs) from human pluripotent stem cells by stage-specific manipulation of developmental signaling pathways. SANLPCs are identified as NKX2-5⁻ cardiomyocytes that express markers of the SAN lineage and display typical pacemaker action potentials, ion current profiles and chronotropic responses. When transplanted into the apex of rat hearts, SANLPCs were able to pace the host tissue, demonstrating their capacity to function as a biological pacemaker. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

Influence of Donor Age on Induced Pluripotent Stem Cells

To explore the impact of age on iPSC quality, investigators produced induced pluripotent stem cells (iPSCs) from blood cells of 16 donors aged 21–100. They found that iPSCs from older donors retain an epigenetic signature of age, which can be reduced through passaging. Clonal expansion via reprogramming also enables the discovery of somatic mutations present in individual donor cells, which are missed by bulk sequencing methods. [Nat Biotechnol] Abstract

Self-Organized Amniogenesis by Human Pluripotent Stem Cells in a Biomimetic Implantation-Like Niche

Scientists report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. They showed that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. [Nat Mater] Abstract

β-Cell–Mimetic Designer Cells Provide Closed-Loop Glycemic Control

Investigators achieved glucose responsiveness by a synthetic circuit that couples glycolysis-mediated calcium entry to an excitation-transcription system controlling therapeutic transgene expression. Implanted circuit-carrying cells corrected insulin deficiency and self-sufficiently abolished persistent hyperglycemia in type 1 diabetes mice. [Science] Abstract | Press Release

Dickkopf-1 Promotes Hematopoietic Regeneration via Direct and Niche-Mediated Mechanisms

Scientists showed that deletion of the pro-apoptotic genes Bak and Bax in osterix-expressing cells in mice promotes hematopoietic stem cell regeneration and hematopoietic radioprotection following total body irradiation. Treatment of irradiated hematopoietic stem cells (HSCs) with Dkk1 in vitro increased the recovery of both long-term repopulating HSCs and progenitor cells, and systemic administration of Dkk1 to irradiated mice increased hematopoietic recovery and improved survival. [Nat Med] Abstract | Press Release

Mesenchymal Stem Cell Transplantation Can Restore Lupus Disease-Associated miRNA Expression and Th1/Th2 Ratios in a Murine Model of SLE

The authors compared the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells, and cyclophosphamide treatment in C3.MRL-Fas^lpr/J mice using a murine systemic lupus erythematosus model. [Sci Rep] Full Article

The Secretome of Periodontal Ligament Stem Cells from MS Patients Protects against EAE

Researchers showed that human periodontal ligament stem cells-derived conditioned medium and purified exosomes/microvesicles obtained from Relapsing Remitting-multiple sclerosis (MS) patients and healthy donors block experimental autoimmune encephalomyelitis, a mouse model of MS, by inducing anti-inflammatory and immunosuppressive effects in spinal cord and spleen, and reverse disease progression by restoring tissue integrity via remyelination in the spinal cord. [Sci Rep] Full Article

Preclinical Evaluation of Radiation and Systemic, RGD-Targeted, Adeno-Associated Virus Phage-TNF Gene Therapy in a Mouse Model of Spontaneously Metastatic Melanoma

Researchers demonstrated that the combination of RGD-targeted adeno-associated virus phage with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. [Cancer Gene Ther] Abstract

Tailored Transgene Expression to Specific Cell Types in the Central Nervous System after Peripheral Injection with AAV9

Without a well-tailored system, the use of a peripheral route injection may lead to undesirable transgene expression in nontarget cells or organs. To refine this approach, investigators characterized the transduction profiles of new self-complementary AAV9 expressing the green fluorescent protein either under an astrocyte or neuronal promoter, after intravenous injection of adult mice. [Mol Ther Methods Clin Dev] Full Article

Dynamics of Antigen Presentation to Transgene Product-Specific CD4⁺ T Cells and of Treg Induction upon Hepatic AAV Gene Transfer

Scientists administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells. They found that that the liver-draining lymph nodes are the major sites of MHC II presentation of the virally encoded antigen, as judged by in vivo proliferation of DO11.10 CD4⁺ T cells and CD4⁺CD25⁺FoxP3⁺ Treg induction. [Mol Ther Methods Clin Dev] Full Article

Patient-Derived Induced Pluripotent Stem Cells in Cancer Research and Precision Oncology

The authors discusses the main advantages and limitations of induced pluripotent stem cells (iPSCs) modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts. They highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology. [Nat Med] Abstract

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

Moffitt Cancer Center Study Shows Promising Clinical Activity, Safety Results of KTE-C19 in Aggressive B-Cell Non-Hodgkin Lymphoma

Anti-cancer therapeutics, such as chimeric antigen receptor (CAR) modified T cells, can be engineered to target tumor-associated antigens to attack and kill cancer cells. This allows for an improved precision medicine approach to treating cancer. Moffitt Cancer Center physician-scientist Fredrick L. Locke, M.D. presented interim results from cohort 2 of the Phase II portion of the ZUMA-1 study, which uses CAR-T therapy for patients with refractory primary mediastinal B-cell lymphoma and transformed follicular lymphoma. [Press release from Moffitt Cancer Center discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release | Abstract

Gamida Cell Presents Positive Data from Phase I/II Study of NiCord^® as a Curative Treatment for Sickle Cell Disease

Gamida Cell announced results from its Phase I/II study of NiCord for sickle cell disease (SCD). The results presented at ASH demonstrated the potential of NiCord as a novel transplant approach for patients with SCD. The study provided a clinical proof of concept that NiCord, which was transplanted with an un-manipulated unit of umbilical cord blood, may enable very rapid engraftment in SCD patients transplanted after myeloablative conditioning. [Press release from Gamida Cell discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Bayer and Versant Ventures Join Forces to Launch Stem Cell Therapy Company BlueRock Therapeutics

Bayer AG and Versant Ventures announced the launch of BlueRock Therapeutics, a next-generation regenerative medicine company that plans to develop best-in-class induced pluripotent stem cell therapies to cure a range of diseases using an industry-leading platform. BlueRock Therapeutics will be led by a world-class team and has assembled its platform through a series of strategic partnerships with academia and industry. [Bayer AG] Press Release

MeiraGTx Expands Neurodegenerative Gene Therapy Pipeline in Alzheimer’s and Parkinson’s Disease in Collaboration with Weill Cornell Medicine

MeiraGTx announced the expansion of its Neurodegenerative Disease gene therapy pipeline. Research into the causes of neurodegenerative disease has converged upon the central idea that misfolded proteins play a critical role in damaging neuronal function and the ultimate progression to neuronal cell death. The new program, a collaboration with Dr. Greg Petsko of Weill Cornell Medicine, targets neurodegenerative disease by altering neuronal protein processing. [MeiraGTx] Press Release

TxCell Signs In-Licensing Global Agreement with Inserm Transfert for Novel Population of Regulatory T Cells

TxCell SA and Inserm Transfert, on behalf of Inserm, the Nantes University and the Nantes CHU, announce the signature of an exclusive worldwide licensing agreement. As per the terms of this agreement, TxCell has been granted an exclusive worldwide license to two patent families filed by the Center for Research in Transplantation and Immunology (CRTI), a center of excellence in the field of transplantation and immunology. [TxCell SA] Press Release

Cedars-Sinai to Expand Evaluation of Cardiac Cell Therapy after Winning $7.3 Million California Institute for Regenerative Medicine Grant

Researchers from the Cedars-Sinai Heart Institute and the Cedars-Sinai Department of Medicine are expanding their ongoing evaluation of a novel cell-based therapeutic candidate into the area of pulmonary arterial hypertension. This work will be supported by a recently awarded $7.3 million grant from the California Institute for Regenerative Medicine. [Cedars-Sinai Medical Center] Press Release

Visikol Inc. Launches Visikol^® HISTO^™ Platform for 3D Histology with Easy to Use Starter Kit

Visikol Inc. has launched Visikol^® HISTO^™, the market’s first portfolio of tissue clearing kits and reagents that can integrate 3D imaging into existing tissue processing workflows. The Visikol HISTO technology requires no special equipment to clear tissue and provides a rapid, non-destructive, easy-to-use process that allows any researcher to add a new dimension to his or her research with the power of tissue clearing. [Visikol Inc. (PR Newswire Association LLC.)] Press Release

Renova Therapeutics Secures Novel AAV Vector License for Use in Metabolic and Cardiovascular Gene Therapy Development

Renova^™ Therapeutics announced that it has obtained a nonexclusive license for a novel adeno-associated virus (AAV) vector developed in the laboratory of professor Mark Kay, M.D., Ph.D., at Stanford University. The company plans to use this vector in development of its paracrine gene therapy product pipeline. [Renova Therapeutics^™] Press Release

Pioneers in Oncolytic Virus and Gene Therapy Fields Announce Formation of IGNITE Immunotherapy Inc., a Company Focused on Oncolytic Cancer Vaccine Discovery and Development

IGNITE Immunotherapy Inc. announced its formation. Along with strategic collaborative partner and lead investor Pfizer Inc., IGNITE will focus on the discovery and development of targeted and proprietary next-generation intravenous oncolytic virus vaccines for the immunotherapy of cancer. These biotherapeutics may be optimized for use in combination with immune checkpoint inhibitors. [IGNITE Immunotherapy Inc. (Business Wire, Inc.)] Press Release

First Ever Employer to Store Lifesaving Stem Cells for Employees

Precious Cells is offering their employees the ultimate employee benefit unlike anything ever seen before. They will cryogenically store employees’ and their loved ones’ stem cells, for free. This means they can be used in treatment for life threatening conditions today, tomorrow and in the future. [Precious Cells (PR Newswire Association LLC.)] Press Release

Brexit by the Numbers: The Fear of Brain Drain

British universities fear losing large swathes of their research staff as the country faces up to Brexit, the split with the European Union. More than 31,000 academics at UK universities are non-British EU citizens, and so may lose their rights to live in the United Kingdom after Brexit. [Nature Trend Watch] Editorial

Italian Scientists Won’t Miss Departing Prime Minister Matteo Renzi

Italian politics is in turmoil after the resignation of Prime Minister Matteo Renzi — but researchers say that they are not particularly sad to see him go. In his almost three years in charge, Renzi promised improvements for universities and science but failed to raise the status of research in the country, according to scientists who complain that he also directly interfered in academic affairs. [Nature News] Editorial

FDA

Agency Information Collection Activities; Proposed Collection; Comment Request; Recommended Glossary and Educational Outreach To Support Use of Symbols on Labels and in Labeling of In Vitro Diagnostic Devices Intended for Professional Use (FR Doc. No:2016-29104) Notice

Agency Information Collection Activities; Proposed Collection; Comment Request; Providing Information About Pediatric Uses of Medical Devices (FR Doc. No:2016-29105) Notice

NEW 19^th International Conference on Clinical Application of Adult Stem Cells
February 14-15, 2017
Havana, Cuba

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

NEW Staff Research Associate III – Translational Research to Clinical Cell Therapies (University of California Davis Health System)

NEW Senior Research Scientist – Otolaryngology (Vanderbilt University Medical Center)

NEW Laboratory Technician – Cellular Production Associate II-III (Fred Hutchinson Cancer Research Center)

Staff Research Associate III – Clinical Gene, Cellular, and Other Pharmaceutical Product Manufacturing (University of California Davis Health System)

Independent Research Group Leaders – Stem Cell Science (University of Cambridge)

Postdoctoral Fellow – Statistical Computing in Cancer Research and Personalized Medicine (European Molecular Biology Laboratory)

GMP Manufacturing Director – Cell and Gene Therapy (Fred Hutchinson Cancer Research Center)

Division Head – Cell Labeling and Sensing (Helmholtz Zentrum München)

Pioneer/Division Head – Human Organoids (Helmholtz Zentrum München)

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)

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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