Cell Therapy News Volume 18.05 | Feb 20 2017

TOP STORY

Targeting CASP8 and FADD-Like Apoptosis Regulator Ameliorates Nonalcoholic Steatohepatitis in Mice and Nonhuman Primates

Scientists report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. They provide mechanistic evidence that CFLAR directly targets the kinase MAP3K5 (also known as ASK1) and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8. [Nat Med] Abstract

(Ranked by impact factor of the journal)

Human γδ T Cells Are Quickly Reconstituted after Stem-Cell Transplantation and Show Adaptive Clonal Expansion in Response to Viral Infection

To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells, researchers applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors before and after transplantation in a prospective cohort study. [Nat Immunol] Abstract

Drug Discovery for Diamond-Blackfan Anemia Using Reprogrammed Hematopoietic Progenitors

Identifying therapeutics for diamond-blackfan anemia (DBA) requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, investigators adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. [Sci Transl Med] Abstract | Press Release

Muscle-Specific CRISPR/Cas9 Dystrophin Gene Editing Ameliorates Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy

The authors developed multiple approaches for editing the Duchenne muscular dystrophy gene in dystrophic mdx^4cv mice using single and dual adeno-associated viral vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. [Nat Commun] Full Article

Preclinical Efficacy Failure of Human CNS-Derived Stem Cells for Use in the Pathway Study of Cervical Spinal Cord Injury

Investigators tested the efficacy of two human CNS neural stem cell lines in cervical spinal cord injury (SCI): one research cell line, and one clinical cell lot/line (CCL) intended for use in the Pathway Study of cervical SCI in man. They assessed locomotor recovery and sensory function, as well as engraftment, migration, and fate. No evidence of efficacy of the CCL was observed; some data suggested a negative impact of the CCL on outcomes. [Stem Cell Reports] Full Article | Graphical Abstract

Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs

The authors showed that bone marrow stromal cells (BMSCs) reverted to a primitive stem cell population elicit stronger homing and glioma-killing effects together with cytosine deaminase/5-fluorocytosine compared with unmanipulated BMSCs in vivo. [Stem Cell Reports] Full Article | Graphical Abstract

Repeated Doses of Cardiac Mesenchymal Cells Are Therapeutically Superior to a Single Dose in Mice with Old Myocardial Infarction

Mice with a three-week-old myocardial infarction received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that investigators have recently described. CMCs or vehicle were infused percutaneously into the left ventricular (LV) cavity, 14 days apart. Compared with vehicle-treated mice, the single-dose group exhibited improved LV ejection fraction after the first infusion but not after the second and third. [Basic Res Cardiol] Abstract

Cryogel-Supported Stem Cell Factory for Customized Sustained Release of Bispecific Antibodies for Cancer Immunotherapy

A macroporous biohybrid cryogel platform displayed effectiveness in supporting proliferation and survival of bispecific antibody (bsAb)-releasing-mesenchymal stromal cells overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33⁺ acute myeloid leukemia blasts. [Sci Rep] Full Article

In Patients with Chronic Aplastic Anemia, Bone Marrow–Derived MSCs Regulate the Treg/Th17 Balance by Influencing the Notch/RBP-J/FOXP3/RORγT Pathway

Mesenchymal stromal cells (MSCs) obtained from bone marrow donors were concentrated and intravenously injected into 15 chronic aplastic anemia (AA) patients who had been refractory to prior immunosuppressive therapy. Researchers showed that bone marrow–derived MSCs modulate the levels of Th1, Th2, Th17 and Treg cells, as well as their related cytokines in chronic AA patients. [Sci Rep] Full Article

The Novel BMI-1 Inhibitor PTC596 Downregulates MCL-1 and Induces p53-Independent Mitochondrial Apoptosis in Acute Myeloid Leukemia Progenitor Cells

PTC596 induced apoptosis in a p53-independent manner. PTC596 induced apoptosis along with the reduction of MCL-1 and phosphorylated AKT in patient-derived CD34⁺CD38^low/− stem/progenitor cells. Mouse xenograft models demonstrated in vivo anti-leukemia activity of PTC596, which inhibited leukemia cell growth in vivo while sparing normal hematopoietic cells. [Blood Cancer J] Full Article

Changes in the Incidence, Patterns and Outcomes of Graft Failure following Hematopoietic Stem Cell Transplantation for Hurler Syndrome

Hematopoietic stem cell transplantation (HSCT) is the standard of care in children with Hurler syndrome (HS) as it is the only therapy that can arrest disease progression. The authors examined the incidence, patterns and outcomes of graft failure in all HS children undergoing first HSCT at the Royal Manchester Children’s Hospital or the University of Minnesota Children’s Hospital from 1983 to 2016. [Bone Marrow Transplant] Abstract

MicroRNA Therapeutics: Towards a New Era for the Management of Cancer and Other Diseases

The authors describe recent advances in their understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. They also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics. [Nat Rev Drug Discov] Abstract

Applications of Induced Pluripotent Stem Cell Technologies in Spinal Cord Injury

The beneficial effect of iPSC-derived neural precursor cell transplantation has been reported from the authors’ group and others working in rodent and non-human primate models. These promising results facilitate the application of iPSCs for clinical applications in spinal cord injury patients. However, iPSCs also have issues, such as genetic/epigenetic abnormalities and tumorigenesis due to the artificial induction method, that must be addressed prior to clinical use. [J Neurochem] Abstract

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

PureTech Health’s Vedanta Biosciences Announces Clinical Translational Medicine Collaborations with Stanford University School of Medicine and Leiden University Medical Center

Vedanta Biosciences announced that it has entered into translational medicine collaborations with Stanford University School of Medicine and Leiden University Medical Center. The relationships will focus on food allergies in children and on patients with C. difficile infection or graft-versus-host disease, respectively. [Vedanta Biosciences] Press Release

Penn Gene Therapy Pioneer Teams Up with FAST in Race to Cure Angelman Syndrome

Downers Grove, a pioneer on the frontier of genetic medicine and his team at one of the nation’s top-five medical research schools have joined forces with FAST to develop a treatment for the rare disorder Angelman syndrome. Researcher James M. Wilson, M.D., Ph.D., has been working for three decades to develop effective strategies to treat and cure genetic diseases. [FAST (Foundation for Angelman Syndrome Therapeutics) (Newswise, Inc.)] Press Release

City of Hope to Manufacture NurOwn^® for Brainstorm’s Phase III ALS Clinical Trial

BrainStorm Cell Therapeutics Inc. announced that it plans to contract with City of Hope’s Center for Biomedicine and Genetics to produce clinical supplies of NurOwn^® adult stem cells for the company’s planned randomized, double-blind, multi-dose Phase III clinical study in patients with Amyotrophic Lateral Sclerosis (ALS). [BrainStorm Cell Therapeutics Inc.] Press Release

Celyad Registers First Hematological Patient in CAR-T NKR-2 THINK Trial

Celyad announced a further step in the CAR-T NKR-2 THINK trial with the registration of a first refractory Multiple Myeloma patient. This patient is expected to receive the first dose-level in the coming weeks, opening the first cohort of the hematological arm of the study. [Celyad] Press Release

MeiraGTx Provides Clinical Trial Updates for Achromatopsia and Leber’s Congenital Amaurosis Ocular Gene Therapy Programs

MeiraGTx announced the first patient in its clinical study for achromatopsia due to mutations in the CNGB3 gene was treated at the Moorfields Eye Hospital in London. The AAV-mediated gene therapy study design for CNGB3 deficiency is an open label, multi-center, Phase I/II dose escalation trial. [MeiraGTx] Press Release

Minerva Biotechnologies Launches AlphaSTEM^™, A Naïve Stem Cell Culture System

Minerva Biotechnologies announced the launch of the AlphaSTEM^™ Culture System. The system uses a newly discovered growth factor that is only expressed in the naïve cells of the inner cell mass during the earliest days of embryogenesis. [Minerva Biotechnologies] Press Release

TapImmune Expands Intellectual Property on PolyStart^™ Platform for Use in Next-Generation T-Cell Vaccines

TapImmune, Inc. announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for its patent application titled, “Chimeric nucleic acid molecules with non-AUG initiation sequences and uses thereof.” [TapImmune, Inc.] Press Release

Upstate Opens Cord Blood Bank in a Ribbon-Cutting Ceremony

Upstate Medical University officially opened the Upstate Cord Blood Bank in a ribbon-cutting ceremony. The $15 million, 20,000 square foot facility features a state of the art processing laboratory and cryogenic storage containers that can store nearly 14,500 units of cord blood. [Upstate Medical University] Press Release

Delay in Hiring Science Advisers Intensifies Brexit Worries

Policy experts want scientists to be at the table when government decides on environmental protection and membership of international collaborations. [Nature News] Editorial

Why the CRISPR Patent Verdict Isn’t the End of the Story

The US Patent and Trademark Office issued a key verdict this week in the battle over the intellectual property rights to the potentially lucrative gene-editing technique CRISPR–Cas9. But the fight for patent rights to CRISPR technology is by no means over. [Nature News] Editorial

FDA

Advisory Committee Nominations; Modification To Process for Collecting and Posting Curricula Vitae (FR Doc. No:2017-02411) Notice

Bioequivalence Recommendations for Difluprednate; Revised Draft Guidance for Industry; Availability (FR Doc. No:2017-02972) Notice

Q11 Development and Manufacture of Drug Substances-Questions and Answers (Regarding the Selection and Justification of Starting Materials); International Council for Harmonisation; Guidance for Industry; Availability (FR Doc. No:2017-03309) Notice

NEW Stem Cells and Regenerative Medicine 2^nd International Congress
April 19-21, 2017
Mashhad, Iran

NEW Stem Cell Summit
April 26-28, 2017
Boston, United States

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

NEW Postdoctoral Positions – Stem Cell Research (Indian Institute of Science Education and Research Thiruvananthapuram)

Assistant Professor – Medicine by Design Junior Chair in Immunobioengineering (University of Toronto)

Associate/Full Professor – Loretta Rogers Chair in Immunobioengineering (University of Toronto)

Medical Director – Clinical Research Physician (Celgene Corporation)

Postdoctoral Fellow – Various Projects (University of Oklahoma)

Scientist – Regulatory Support (Cook MyoSite, Inc.)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

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

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)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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

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