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Archive for the ‘Regenerative Biology and Medicine’ Category


Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders at https://www.amazon.com/dp/B078313281 – electronic Table of Contents 

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

Available on Kindle Store @ Amazon.com since 12/9/2017

List of Contributors & Contributors’ Biographies

Volume Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Preface, all Introductions, all Summaries and Epilogue

Part One:

1.4, 1.5, 1.6, 2.1.1, 2.1.2, 2.1.3, 2.1.4, 2.2.1, 2.2.2, 2.2.3, 2.3, 2.4, 2.4.1, 2.4.2, 2.5, 2.6.1, 2.6.2, 2.6.3, 2.6.4, 2.7, 2.8, 2.9, 2.10, 3.1, 3.2, 3.3, 3.4, 4.1, 4.2, 4.3

Part Two:

5.2, 5.3, 5.6, 6.1.2, 6.1.4, 6.2.1, 6.2.2, 6.3.2, 6.3.4, 6.3.5, 6.3.6, 6.3.8, 6.3.10, 6.4.1, 6.4.2, 6.5.1.2, 6.5.1.3, 6.5.2.2, 7.1, 7.2, 7.3, 7.4, 7.5, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 8.9.1, 8.9.3, 8.9.4, 8.9.5, 8.9.6, 8.10.1, 8.10.2, 8.10.3, 8.10.4, 9.2, 9.3, 9.5, 9.6, 9.7, 9.8, 9.9, 9.10, 9.11, 9.12, 9.13, 9.14, 9.15, 9.16, 10.2, 10.5, 10.6, 10.7, 10.8, 10.10, 10.11, 11.1, 11.2, 11.3, 11.5, 11.6, 11.7, 12.1, 12.2, 12.3, 12.4, 12.5, 12.7, 12.8, 12.9, 12.10, 12.11, 12.12, 13.1, 13.2, 13.3, 13.6, 13.12, 13.13, 14.1, 14.2

Guest Authors:

Pnina Abir-Am, PhD Part Two: 6.1.1

Stephen J Williams, PhDPart Two: 6.2.6, 6.5.2.2, 10.4, 10.9, 13.4

Aviva Lev-Ari, PhD, RN:

Part One:

1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2.2.1, 2.3

Part Two:

5.1, 5.4, 5.5, 5.7, 5.8, 5.9, 5.10, 5.11, 6.1.3, 6.2.3, 6.2.4, 6.2.5, 6.3.1, 6.3.3, 6.3.7, 6.3.9, 6.4.3, 6.5.1.1, 6.5.2.1, 6.5.2.2, 6.5.3.1, 6.5.4, 6.5.5, 6,5,6, 8.9.2, 8.10.2, 9.1, 9.4, 10.1, 10.3, 11.4, 12.6, 13.5, 13.7, 13.8, 13.9, 13.10, 13.11

Adam Sonnenberg, BSC, MSc(c)Part Two: 13.9

 

electronic Table of Contents

PART ONE:

Physician as Authors, Writers in Medicine and Educator in Public Health

 

Chapter 1: Physicians as Authors

Introduction

1.1  The Young Surgeon and The Retired Pathologist: On Science, Medicine and HealthCare Policy – Best writers Among the WRITERS

1.2 Atul Gawande: Physician and Writer

1.3 Editorial & Publication of Articles in e-Books by  Leaders in Pharmaceutical Business Intelligence:  Contributions of Larry H Bernstein, MD, FCAP

1.4 Abraham Verghese, MD, Physician and Notable Author

1.5 Eric Topol, M.D.

1.6 Gregory House, MD

1.7 Peter Mueller, MD  Professor of Radiology @MGH & HMS – 2015 Synergy’s Honorary Award Recipient

Summary

Chapter 2: Professional Recognition

Introduction

2.1 Proceedings

2.1.1 Research Presentations

2.1.2 Proceedings of the NYAS

2.1.3 Cold Spring Harbor Conference Meetings

2.1.4 Young Scientist Seminars

2.2 Meet Great Minds

2.2.1 Meet the Laureates

2.2.2 Richard Feynman, Genius and Laureate

2.2.3 Fractals and Heat Energy

2.3 MacArthur Foundation Awards

2.4 Women’s Contributions went beyond Rosie the Riveter

2.4.1 Secret Maoist Chinese Operation Conquered Malaria

2.4.2 Antiparasite Drug Developers Win Nobel

2.5 Impact Factors and Achievement

2.6   RAPsodisiac Medicine

2.6.1 Outstanding-achievements-in-radiology-or-radiotherapy

2.6.2 Outstanding-achievement-in-anesthesiology

2.6.3 Outstanding-achievement-in-pathology

2.6.4 Topics in Pathology – Special Issues from Medscape Pathology

2.7 How to win the Nobel Prize

2.8 Conversations about Medicine

2.9 Current Advances in Medical Technology

2.10 Atul Butte, MD, PhD

Summary

Chapter 3:  Medical and Allied Health Sciences Education

Introduction

3.1 National Outstanding Medical Student Award Winners

3.2 Outstanding Awards in Medical Education

3.3 Promoting Excellence in Physicians and Nurses

3.4 Excellence in mentoring

Summary

Chapter 4: Science Teaching in Math and Technology (STEM)

Introduction

4.1 Science Teaching in Math and Technology

4.2 Television as a Medium for Science Education

4.2.1 Science Discovery TV

4.3 From Turing to Watson

Summary

PART TWO:

Medical Scientific Discoveries Interviews with Scientific Leaders

Chapter 5: Cardiovascular System

Introduction

5.1 Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem

5.2 Mitochondrial Dysfunction and Cardiac Disorders

5.3 Notable Contributions to Regenerative Cardiology

5.4 For Accomplishments in Cardiology and Cardiovascular Diseases: The Arrigo Recordati International Prize for Scientific Research

5.5 Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

5.6 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

5.7 CVD Prevention and Evaluation of Cardiovascular Imaging Modalities: Coronary Calcium Score by CT Scan Screening to justify or not the Use of Statin

5.8 2013 as A Year of Revolutionizing Medicine and Top 11 Cardiology Stories

5.9 Bridging the Gap in Medical Innovations – Elazer Edelman @ TEDMED 2013

5.10 Development of a Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinoma PIs: Jeffrey Clark (MGH), Robert Langer (Koch), Elazer Edelman (Harvard:MIT HST Program)

5.11 Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

Summary

Chapter 6: Genomics

Introduction
6.1 Genetics before the Human Genome Project

6.1.1 Why did Pauling Lose the “Race” to James Watson and Francis Crick? How Crick Describes his Discovery in a Letter to his Son

6.1.2 John Randall’s MRC Research Unit and Rosalind Franklin’s role at Kings College

6.1.3 Interview with the co-discoverer of the structure of DNA: Watson on The Double Helix and his changing view of Rosalind Franklin

6.1.4 The Initiation and Growth of Molecular Biology and Genomics, Part I

6.2 The Human Genome Project: Articles of Note  @ pharmaceuticalintelligence.com by multiple authors

6.2.1 CRACKING THE CODE OF HUMAN LIFE: The Birth of BioInformatics & Computational Genomics

6.2.2 What comes after finishing the Euchromatic Sequence of the Human Genome?

6.2.3 Human Genome Project – 10th Anniversary: Interview with Kevin Davies, PhD – The $1000 Genome

6.2.4 University of California Santa Cruz’s Genomics Institute will create a Map of Human Genetic Variations

6.2.5 Exceptional Genomes: The Process to find them

6.2.6 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

6.3 The Impact of Genome Sequencing on Biology and Medicine

6.3.1 Genomics in Medicine – Establishing a Patient-Centric View of Genomic Data

6.3.2 Modification of genes by homologous recombination – Mario Capecchi, Martin Evans, Oliver Smithies

6.3.3 AAAS February 14-18, 2013, Boston: Symposia – The Science of Uncertainty in Genomic Medicine

6.3.4 The Metabolic View of Epigenetic Expression

6.3.5  Pharmacogenomics

6.3.6 Neonatal Pathophysiology

6.3.7 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

6.3.8 3D mapping of genome in combine FISH and RNAi

6.3.9 Human Variome Project: encyclopedic catalog of sequence variants indexed to the human genome sequence

6.3.10 DNA mutagenesis and DNA repair

6.4 Scientific Leadership Recognition for Contributions to Genomics

6.4.1 Interview with Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak (44 minutes)

6.4.2 DNA Repair Pioneers Win Nobel – Tomas Lindahl, Paul Modrich, and Aziz Sancar 2015 Nobel Prize in Chemistry for the mechanisms of DNA repair

6.4.3  Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

6.5 Contemporary Field Leaders in Genomics

6.5.1 ROBERT LANGER

6.5.1.1 2014 Breakthrough Prizes Awarded in Fundamental Physics and Life Sciences for a Total of $21 Million – MIT’s Robert Langer gets $3 Million

6.5.1.2 National Medal of Science – 2006 Robert S. Langer

6.5.1.3  Confluence of Chemistry, Physics, and Biology

6.5.2 JENNIFER DOUDNA

6.5.2.1 Jennifer Doudna, cosmology teams named 2015 Breakthrough Prize winners

6.5.2.2 UPDATED – Medical Interpretation of the Genomics Frontier – CRISPR – Cas9: Gene Editing Technology for New Therapeutics

6.5.3 ERIC LANDER

6.5.3.1  2012 Harvey Prize in April 30: at the Technion-Israel Institute of Technology to Eric S. Lander @MIT & Eli Yablonovitch @UC, Berkeley

6.5.4 2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

6.5.5 Recognitions for Contributions in Genomics by Dan David Prize Awards

6.5.6   65 Nobel Laureates meet 650 young scientists covering the fields of physiology and medicine, physics, and chemistry, 28 June – 3 July, 2015, Lindau & Mainau Island, Germany

Summary

Chapter 7: The RNAs

Introduction

7.1 RNA polymerase – molecular basis for DNA transcription – Roger Kornberg, MD

7.2  One gene, one protein – Charles Yanofsky

7.3 Turning genetic information into working proteins – James E. Darnell Jr.

7.4 Small but mighty RNAs – Victor Ambros, David Baulcombe, and Gary Ruvkun, Phillip A. Sharp

7.5 Stress-response gene networks – Nina V. Fedoroff

Summary

Chapter 8: Proteomics, Protein-folding, and Cell Regulation
Introduction.

8.1 The Life and Work of Allan Wilson

8.2 Proteomics

8.3 More Complexity in Protein Evolution

8.4 Proteins: An evolutionary record of diversity and adaptation

8.5 Heroes in Basic Medical Research – Leroy Hood

8.6 Ubiquitin researchers win Nobel – Ciechanover, Hershko, and Rose awarded for discovery of ubiquitin-mediated proteolysis

8.7 Buffering of genetic modules involved in tricarboxylic acid cycle metabolism provides homeostatic regulation

8.8 Dynamic Protein Profiling

8.9 Protein folding

8.9.1 Protein misfolding and prions – Susan L. Lindquist, Stanley B. Prusiner

8.9.2 A Curated Census of Autophagy-Modulating Proteins and Small Molecules Candidate Targets for Cancer Therapy

8.9.3 Voluntary and Involuntary S-Insufficiency

8.9.4 Transthyretin and Lean Body Mass in Stable and Stressed State

8.9.5 The matter of stunting in the Ganges Plains

8.9.6 Proteins, Imaging and Therapeutics

8.10 Protein Folding and Vesicle Cargo

8.10.1 Heat Shock Proteins (HSP) and Molecular Chaperones

8.10.2 Collagen-binding Molecular Chaperone HSP47: Role in Intestinal Fibrosis – colonic epithelial cells and sub epithelial myofibroblasts

8.10.3 Biology, Physiology and Pathophysiology of Heat Shock Proteins

8.10.4 The Role of Exosomes in Metabolic Regulation 


Summary

Chapter 9:  Neuroscience

Introduction

9.1 Nobel Prize in Physiology or Medicine 2013 for Cell Transport: James E. Rothman of Yale University; Randy W. Schekman of the University of California, Berkeley; and Dr. Thomas C. Südhof of Stanford University

9.2 Proteins that control neurotransmitter release – Richard H. Scheller

9.3 Heroes in Basic Medical Research – Robert J. Lefkowitz

9.4 MIND AND MEMORY: BIOLOGICAL AND DIGITAL – 2014 Dan David Prize Symposium

9.5 A new way of moving – Michael Sheetz, James Spudich, Ronald Vale

9.6 Role the basal ganglia

9.7 The Neurogenetics of Language – Patricia Kuhl – 2015 George A. Miller Award

9.8 The structure of our visual system

9.9 Outstanding Achievement in Schizophrenia Research

9.10 George A. Miller, a Pioneer in Cognitive Psychology, Is Dead at 92

9.11 – To understand what happens in the brain to cause mental illness

9.12 Brain and Cognition

9.13 – To reduce symptoms of mental illness and retrain the brain

9.14 Behavior

9.15 Notable Papers in Neurosciences

9.16 Pyrroloquinoline quinone (PQQ) – an unproved supplement

Summary

Chapter 10: Microbiology & Immunology

Introduction

10.1 Reference Genes in the Human Gut Microbiome: The BGI Catalogue

10.2 Malnutrition in India, high newborn death rate and stunting of children age under five years

10.3 In His Own Words: Leonard Herzenberg, The Immunologist Who Revolutionized Research, Dies at 81

10.4 Heroes in Medical Research: Dr. Robert Ting, Ph.D. and Retrovirus in AIDS and Cancer

10.5 Tang Prize for 2014: Immunity and Cancer

10.6 Halstedian model of cancer progression

10.7 The History of Hematology and Related Sciences

10.8 Pathology Emergence in the 21st Century

10.9 Heroes in Medical Research: Barnett Rosenberg and the Discovery of Cisplatin

10.10  T cell-mediated immune responses & signaling pathways activated by TLRs – Bruce A. Beutler, Jules A. Hoffmann, Ralph M. Steinman

10.11 Roeder – the coactivator OCA-B, the first cell-specific coactivator, discovered by Roeder in 1992, is unique to immune system B cells

Summary

Chapter 11: Endocrine Hormones

Introduction

11.1 Obesity – 2010 Douglas L. ColemanJeffrey M. Friedman

11.2 Lonely Receptors: RXR – Jensen, Chambon, and Evans – Nuclear receptors provoke RNA production in response to steroid hormones

11.3 The Fred Conrad Koch Lifetime Achievement Award—the Society’s highest honor—recognizes the lifetime achievements and exceptional contributions of an individual to the field of endocrinology

11.4 Gerald D Aurbach Award for Outstanding Translational Research

11.5 Roy O. Greep Award for Outstanding Research in Endocrinology – Martin M. Matzuk

11.6 American Physiology Society Awards

11.7 Solomon Berson and Rosalyn Yalow

Summary

Chapter 12. Stem Cells

Introduction

12.1 Mature cells can be reprogrammed to become pluripotent – John Gurdon and Shinya Yamanaka

12.2 Observing the spleen colonies in mice and proving the existence of stem cells – Till and McCulloch

12.3 McEwen Award for Innovation: Irving Weissman, M.D., Stanford School of Medicine, and Hans Clevers, M.D., Ph.D., Hubrecht Institute

12.4 Developmental biology

12.5  CRISPR/Cas-mediated genome engineering – Rudolf Jaenisch

12.6 Ribozymes and RNA Machines –  Work of Jennifer A. Doudna

12.7 Ralph Brinster, ‘Father of Transgenesis’

12.8 Targeted gene modification

12.9 Stem Cells and Cancer

12.10 ALPSP Awards

12.11 Eppendorf Award for Young European Investigators

12.12 Breaking news about genomic engineering, T2DM and cancer treatments

Summary
Chapter 13: 3D Printing and Medical Application

Introduction

13.1 3D Printing

13.2 What is 3D printing?

13.3 The Scientist Who Is Making 3D Printing More Human

13.4 Join These Medical 3D Printing Groups on Twitter and LinkedIn for great up to date news

13.5 Neri Oxman and her Mediated Matter group @MIT Media Lab have developed a technique for 3D-printing Molten Glass

13.6 The ‘chemputer’ that could print out any drug

13.7 3-D-Bioprinting in use to Create Cardiac Living Tissue: Print your Heart out

13.8 LPBI’s Perspective on Medical and Life Sciences Applications – 3D Printing: BioInks, BioMaterials-BioPolymer

13.9 Medical MEMS, Sensors and 3D Printing: Frontier in Process Control of BioMaterials

13.10 NIH and FDA on 3D Printing in Medical Applications: Views for On-demand Drug Printing, in-Situ direct Tissue Repair and Printed Organs for Live Implants

13.11 ‘Pop-up’ fabrication technique trumps 3D printing

13.12 Augmentation of the ONTOLOGY of the 3D Printing Research

13.13 Superresolution Microscopy

Summary

Chapter 14: Synthetic Medicinal Chemistry

Introduction

14.1 Insights in Biological and Synthetic Medicinal Chemistry

14.2 Breakthrough work in cancer

Summary to Part Two

Volume Summary and Conclusions

EPILOGUE

 

 

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LIVE Key Note Presentations @Biotech Week Boston, October 5, 2016 3:25PM

Boston Convention and Exhibition Center

 

#BiotechWeekBoston

 avivalev-ari@alum.berkeley.edu

@pharma_BI

@AVIVA1950

ANNOUNCEMENT

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

pharma_bi-background0238

will cover in REAL TIME

Biotech Week Boston, October 5, 2016 @ Boston Convention and Exhibition Center

 

In Attendance, streaming LIVE using Social Media

Aviva Lev-Ari, PhD, RN

Editor-in-Chief

http://pharmaceuticalintelligence.com

 

Key Sessions

Arnold I. Caplan, Ph.D.

Adult Mesenchymal Stem Cells: The New Medicine

Case Western Reserve University

  • HSC – hematopoietic Stem Cells
  • MSC – mesengenic in vitro not in Tissue Engineering – can be derived from multiple tissue sources
  1. all MSC are Pericytes cells on capillaries and microvessels – CD34 CD146
  2. during injury – pericyte – differentiates – sentinal fro damage and innate tissue regenerations, sense environment
  3. MSC = Medicinal Signaling Cell – the injury specific – 655 Clinical Trials – KIDNEY AND OTHER ORGAN TRANSPLANTATION
  4. hCAP-18/LL37 is secreted by hMSCs
  5. LL37 is in Maternal milk and prevent infection in neonatals
  6. Lipoaspirate
  7. immunomodulatory and Trophic activity
  8. Universal Stem Cell Niche pMSC, Niche
  9. MSCs in cancer metastasis: BRCA, prostate and Melanoma (binding protein) – pericyte pull
  10. http://www.ctte

David DiGiusto, Ph.D.

Building a Sustainable Academic Engine for Feeding De-Risked Assets into the Biopharma Pipeline

Stanford Health Care / Stanford School of Medicine, Cell and Gene Medicine

  1. viral vector
  2. bacterial culture
  3. standard tissue
  • Risks of developing Academic Cell Therapy Products
  • Center for Definitive and Curative Medicine – Regenerative Medicine
  1. translational Staging Score: min 6 points
  2. Scientific Review and Prioritization: 0-9 points
  • Lentiviral vector mediated FOXP3 converts T effector cells into T regulatory cells – CD4 LV-FOXP3
  • CD34 CD90+ blood stem cells: ADM of alpha CD117mAB 0 transplant HSC
  • Cancer Immunotherapy: CD19/CD@@: Leukemia
  • cell transduction
  • Vector Production
  • Plasmid Production
  • Skin DEBnb- low keratinocyte stem cells – neoantigen
  • COmbining CRISPR/Cas9 and rAAV6 mediates High Targeting Efficiencies into peripheral blood CD34+ +HSPCs
  1. Cutting: mRNA and RNP
  2. recombination – AAV only, mRNA : Total population vs Sorted GFP(high)  – get 95% due to Gene correction
  3. Genome editing:
  • starting DNA
  • Edited DNA
  • Edited Protein

4. Closed systems, scalable technology, reagents and automation, clean reagents

5. Invest in the Delivery Channel: Basic Research, Product development, clinical research

6. Transplantation Blood and marrow

7. Cell pharmacy

8. Translational Research : Funding Mix Commercialization, licensing and commercial

9. Infrastructure utilized by every stage of development is different

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LIVE 9/20 2PM to 5:30PM New Viruses for Therapeutic Gene Delivery at CHI’s 14th Discovery On Target, 9/19 – 9/22/2016, Westin Boston Waterfront, Boston

http://www.discoveryontarget.com/

http://www.discoveryontarget.com/crispr-therapies/

Leaders in Pharmaceutical Business Intelligence (LPBI) Group is a

Media Partner of CHI for CHI’s 14th Annual Discovery on Target taking place September 19 – 22, 2016 in Boston.

In Attendance, streaming LIVE using Social Media

Aviva Lev-Ari, PhD, RN

Editor-in-Chief

http://pharmaceuticalintelligence.com

#BostonDOT16

@BostonDOT

 

COMMENTS BY Stephen J Williams, PhD

Gene Therapy Breakthroughs

New Strategies for Better Specificity and Delivery

 

2:05  Chairman’s Remarks

Joseph Gold, Ph.D. Director Manufacturing Center for Biomedicine and Genetics, Beckman Research Institute City of Hope

 

  • CBG (center for biomedicine and Genetics) 20000 sq feet
  • CTPC (center therapy production) mainly CART
  • CBG 16 years operation do all stem cells and >400 products
  • New stem cell Beta cell progenitor
  • Do oncolytic VSV
  • CTPC is investigator driven CART islet cells,
  • Like to do novel work so work with CIRM
  • Banking of modified stem cells
  • Adherent scale out limitations: cost,inefficient; solution can be suspension
  • Establish hESC; plate on CELLstart > Accutase>StemPRO SFM>differentiation process; defined reagents — they use this for cardiomyocyte differentiation: they are functional (inotropy, chronotropy response to isoproterenol) can freeze back cells
  • Create a bank of intermediate cells and when you need it for surgery they will put on their matrix, enrich, expand and ship out
  • Allogeneic cells: project where take allogeneic neural stem cells to deliver a chemotherapy payload as they like to migrate to brain tumors
  • Allogeneic cells: for ALS modified to express GDNF
  • HIV resistance with engineered CCR5 negative blood stem cells
  • Release assay considerations: viability, sterility, if cryopreserved then can determine identity, viral insertions, VSV-G copy number, endotoxin and potency (FDA is wanting phase I potency assays) for CART potency is % transduced
  • Good in vivo activity of the neural stem cells loaded with chemotherapeutic

 

ALS  

  • If deliver GDNF to muscle  using genetically modified myoblasts
  • Best to use fetal stem cells – less issues

 

Canavan disease: progressive fatal neurologic disorder that begins in infancy and don’t make it past teenage years

  • Rossbach is taking autologous cells reprogramming generating iPS cells and then modifying by CRISPR but the CRISPR issues of off target effects persist as well the time required for process and verification; also don’t want to use a selectable marker and put in patients; so you can differentiate the cells and hit them with a lentiviral vector system

 

They have been named a PACT Center Production Assistance for Cell Therapy where you can apply for a project grant.  Applicable for startups up to larger mature companies

www.pactgroup.net

 

They do a standard panel of tests for viral infections.

They work with investigators or companies at all stages of manufacturing processes.

 

@BeckmanInst

@cityofhope

 

2:15 Large-Scale Production of Cell Therapies for Regenerative Medicine

Joseph Gold, Ph.D. Director Manufacturing Center for Biomedicine and Genetics, Beckman Research Institute

 

2:45  Directed Evolution of New Viruses for Therapeutic Gene Delivery

David Schaffer, Ph.D.  Professor of Chemical and Biomolecular Engineering, BioEngineering, Molecular and Cell Biology and Neuroscience;

 

AAV is very safe as many people already infected with it

 

  • Spark (Leber’s cogenital anaurosis
  • Hemophilia B
  • Lipoprotein lipase deficiency
  • Spinal muscular atrophy
  • Challenges: are we just getting the ‘low hanging fruit’ eg Spark therapy must be injected after retinal therapy, hemo B needs to be given at high doses
  • Their theory was AAV had been evolving for its own purposes so hence the limitations of AAV;
  • Utilized 25 different techniques to generate variants of AAV in a library then packaged (each will have its own barcode)
  • Broad platform technology: retina, lung, brain and spinal cord

Retinal:  AAV may be too large to get through layers of the eye, problems; subretinal injections and damage or retinal detachment.  Then they used their whole library in an in-vivo screen (as hard to recapitulate the multi cell layers of the retina).  

 

Cystic Fibrosis

  • AAV2H22 variant worked very well to supply the CFTR gene in pig model of cystic fibrosis and increases chloride transport and reduce bacterial load
  • Then found pig variant AAV did not work well on human tissue so designed a human variant and worked well in human tissues
  • The variant AAV2.5T surrounds sialic acid binding pockets and increases binding and endocytosis

 

Brain and Spinal Cord:  Sanfilippo B trial  8 holes drilled into skull followed by 16 AAV injections

 

  • Injected a generated AAV variant (by evolution process) : engineered AAV2 is 100 fold better getting through blood brain barrier… novel variant undergoes retrograde transport to cortex ; made a cas9 to remove a tdTomato gene overexpressed in mouse and found 90% knockdown
  • Also interesting point: the porcine variant did not work in human and the human variant did not work in porcine.  Implication for FDA safety and efficacy testing must do in monkeys

They started a spinout 4D Molecular Therapeutics

 

4:25 Lentiviral Vectors for Gene Therapy

 

Munapaty Swani, Ph.D. Texas Tech Health Science Center

 

  • Can express multiple shRNA under a separate promoter but toxic so if expressed in miRNA backbone could be safer under a pol II
  • How much of flanking sequence is needed?
  • 30 nt flanking sequence is enough for Drosha processing
  • Constructed 1 to 7 shRNA-miR targeting CCR5 and 6 viral genes; all constructs were functional
  • Problem with pol ii promoter
  • These 7 shRNA miRNA protect against HIV entry if against CCR5 and the 7 viral elements
  • Used the non-integrating lentivirus for transient to see if infect T cells or not versus integrating lentivirus ; results non-integrating lentivirus did not infect t cells so safer to use
  • CCR5 disruption reduced HIV infection in T cells in vitro;
  • ZFN treatment of HIV+ PBMC prevents activation of HIV
  • Encapsulted CAS9 within LV; cas9 protein is incorporated within LV and is functional
  • First transduce then come in with the Cas9 so made all in one lentivirus with Cas9 and an sgRNA expression vector *******
  • This shows that it is possible to put all in a nanoparticle based lentivirus and an all in one may make it easier and safer (supposedly)

 

4:55 AAV Capsid Design

Miguel Seria Esteves, PhD Associate Professor Neurology, Gene Therapy Center University of Massachusetts Medical School

 

-AAV replication dependent no known human disease with native AAV

  •  Multiple barriers to get across blood brain barrier
  • AAV9 preferentially target neonatal neurons and adult astrocytes
  • Multiple capsids can be used for AAV9 infection in brain but not complete
  • Can we design better capsids to give it better tropic properties and better penetration to blood brain barrier
  • Using a polyalanine in the 5’ end of the caspid was most efficeint
  • Increases gene transfer efficiency especially IN SELECT CELL TYPES; Glial transduction and increased in striatum: increase is structure specific so little in thalamus but good in cerebellum and spinal cord
  • AAV9 tranduces also in peripheral tissues with or without modified capsid

 

Huntington’s Disease

  • Polyglutamate disease polyy glu on huntingtin protein
  • They get a 40 to 50% reduction of huntingtin but not significant between capsid design
  • They did a directed evolution of AAV capsid and generated capsid gene delivery diversity: DNA shuffling and in vivo selection
  • AAV-B1 is a new tropic capsid showing transduction of different structures
  • Five fold reduction in tropism to the liver but massive increases in muscle and beta exocrine cells and lung
  • Presence of neutralizing antibodies is a problem with AAV therapy
  • In conclusion unknown mechanisms by whivh a highly hydrophobic string of 19 alanines modifies the CHS tropism of AAV9 kvariants
  • Chimeric capsids identified from in vivo screen can reveal interesting patterns of tropism

12:45 PM Screening with shRNA and CRISPR

Ryan Raver, PhD Global Product Manager, Functional Genomics, MilliporeSigma

  • KO – Knock Out
  • KD – Knock Down
  1. RNAi -KD
  2. CRISPR-Cas9 – KO

NEW STRATEGIES FOR BETTER SPECIFICITY AND DELIVERY

2:05 Chairperson’s Remarks

Joseph Gold, Center for Biomedicine and Genetics Beckman Research Institute, City of Hope

2:15 Large Scale Production of cell Therapies for Regenerative Medicine: COmbination Cell and Gene Therapy products

Joseph Gold, Center for Biomedicine and Genetics Beckman Research Institute, City of Hope

  • Biological & Cellular GMP manufacturing Core at COH
  • Establishing scalable hESC suspension Culture
  • Optimized small molecule concentration, induction timing, stirring rates
  1. Almost Xeno free
  2. defined
  3. very good reproducibility
  4. high purity and yield:
  • Immuno-staining,
  • FACS – cTnT, sMHC, Alpha-actinin
  • Cryopreservation, Multi-electrode Array (MEA)
  • hESC-RPE monolayer on synthetic substrate

Combination cell/gene therapy products at COH

  1. CAR T CCR5-inactivated CD34+ HSPC – Target: AIDS
  • adoptive immunotherapy using CAR-Engineering T cells – glioblastoma

2. HIV resistance with engineering CCR5-negative blood stem cells: gene KO by ZFNs

  • assay considerations 0 If cryopreservation : Identify, viral insertion, endotoxin, residual beads Potency: CAR T- % transduced cells, CCR5-?-CD34 cells: HIV resistance

3. Glioblastoma

4.  In vivo activity of transduced NSCs: Assay consideration – viability, sterility, mycobatom,

5.  ALS: degeneration of neurones

  • Embryonic stem cells
  • Fetal neural stem cells
  • Adult stem cells – human Proginetor neural cells

6.  Canavan Disease – Y.Shi – ASPA gene mutations cause Canavan disease

Strategy: autologous iPSC-derived, modified neural progenitors: DIferentiate to neural progenitors

Gene therapy: Correction (Off-taregt effects, correct individual cell lines)  or Over expression (Copy number, selection, transduce iPSC)

  • release assay consideration
  • identity – markers and HLA, contaminants, Potency: in vivo efficacy modified autologous
  • production Assistance for Cell therapy
  • cell therapy manufacturing development
  • roles of Biobanks

 

2:45 Directed Evolution of New Viruses for Therapeutic Gene Delivery

David Schaffer, Ph.D., Professor of Chemical and Biomolecular Engineering, Bioengineering, Molecular and Cell Biology, and Neuroscience; Director, Berkeley Stem Cell Center, University of California, Berkeley

Adeno-associated viral (AAV) vectors have been increasingly successful in clinical trials; however, viruses face many delivery barriers that limit their efficacy for most disease targets. We have developed directed vector evolution – the iterative genetic diversification of a viral genome and functional selection for desired properties – to engineer novel, optimized AAV vectors for efficient, selective delivery for a range of tissue and disease targets.

  • DNA (gene therapy and editing) >> RNAi (antisense) >> Protein: Small molecules and monoclonal antibodies
  • Dlivery
  • Adeno Associated Viral Vectors Adenoviral helper genes
  • AAV2, efficacy in Leber’s Congenital samaurosis (AAV)
  • Spinal muscular, lipolrotein lipase deficiency (AAV)

Gene Delivery

  1. neutralization of pre-esisting antibodies
  2. target tissue – deep penetration
  3. Inefficient transduction to target cells
  4. target specific cells

Fitness as Therapy – virus evolutionary: Tropism and immunity

  • AAV directed Vector evolution : Input /sequence >> Diversity/generation >> Packaging
  • Retinoschisis Model – Eye therapeutic gene to protect vision – AAV – transduction of retinal cell, vitreas in Human different scale — eventually Macualr degeneration Therapy for: Photo receptor is the target for therapy
  • Dog: Fundus Imaging of Engineered AAV: Variant Expression GFP Pool Carrying

Lung- Cystic Fibrosis (mucus production amplifies (enhanced transduction) due to MAC3 translation error) – Gene Therapy – cilia function to restore ability to clear mucos: Variant evolved on Human airway epithelia – AA  particles

  1. AAV2>>> AAV%>> T mutation
  • efficacy must be improved

Brain and Spinal Cord

  1. Scull – 8 drills followed by 16 AAV injections
  2. Spinal cord: injuction in muscle

Synthetic version of AAV — Engineered AAV for enhanced Retrograde Transport

  • AAV2-retrograded transport – Noval variant Undergoes Transport along multiple Projections
  • Cas9 – Retrograde Delivery of Cas9 to cortex of mouse – KD –

Summary

  • Virus as gene delivery mechanism
  • designer AAV variants

 

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

4:25 Lentiviral Vectors for Gene Therapy

Manjunath N. Swamy, MD, Professor of Biomedical Sciences and Co-DIrector of the Center of Emphasis in Infectious Diseases. Paul L Foster School of Medicine, Texas Tech University Health Science Center

  • RNAi targets for HIV
  • Expression of multiple shRNAs
  • COnstruction od 7 shRNA-miR targeting CCR5 and 6 viral genes – protect against both 5 ans x4 tropic HIV-1
  • shRNA expression does not decrease with distance from promoter
  • Lentiviral vector to express ZFNs: HIV envelop – ZFN-mediated CCR5 gene editing in Primary T cells
  • ZFN treatment of HIV+PBMC prevents activation of HIV
  • Strategy to encapsulate Cas9 Protein wihtin LV : AIm to deliver Cas9 protein deliver sgRNA expression vector. A Lentiviral
  • Gene editing by all-in-one Lentivirus = to prepack

 

4:55 AAV Caspid Engineering

Miguel Sena Esteves, Ph.D., Associate Professor, Department of Neurology, Gene Therapy Center, University of Massachusetts Medical School

Adeno-associated virus vectors have become the leading platform for development of in vivo gene therapies for neurological diseases. We have developed new AAV vectors for widespread gene delivery to the CNS through vascular infusion in adult animals through peptide grafting and in vivo library selection. These new neurotropic AAVs have achieved CNS-wide silencing of gene expression using gene-specific microRNAs.

  • Adeno-associated virus – Paravovirus family
  • Recombinant AAV vectors carry gene expression cassette of choice flanked by two
  • CNS – route of gene delivery
  • Crossing BBB
  • Systemic delivery of AAV9 vectors: IV
  • Peptide grafting – in vivo selection of novel CNS: DIstribution of GFP transduced cells – robust neuronal transducture with transduction AAV-AS
  • motor cortex, Straiatum, thalamus, motor cortex, ventral horn of spinal cord, cerebelum, liver, muscle, oculomotor nerve, nucleus of oculomotor nerve

Huntington’s Disease > 40 CAG vs <26 CAG in normal – Peptide grafting of AAV vectors for CNS

  • DNA shuffling and in vivo selection: Brain vs Liver

Next generation of AAV vectors for CNS 

  • Liver, pancreas, lung — same pattern

neural transduction after vascular delivery

  • AAV-B1 caspid vs AAV8 – 19 amino acids

Conclusion

New capsids with improved CNS tropism

19 alanines modifies the CNS tropism of AAV9 variants

Chimeric caspids identified from in vivo screens

 

5:25 Welcome Reception in the Exhibit Hall with Poster Viewing

 

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cvd-series-a-volume-iv-cover

Series A: e-Books on Cardiovascular Diseases

Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC

VOLUME FOUR

Regenerative and Translational Medicine

The Therapeutic Promise for

Cardiovascular Diseases

  • on Amazon since 12/26/2015

http://www.amazon.com/dp/B019UM909A

 

by  

Larry H Bernstein, MD, FCAP, Senior Editor, Author and Curator

and

Aviva Lev-Ari, PhD, RN, Editor and Curator

 

Part One:

Cardiovascular Diseases,Translational Medicine (TM) and Post TM

Introduction to Part 1: Cardiovascular Diseases,Translational Medicine (TM) and Post TM

Chapter 1: Translational Medicine Concepts

1.0 Post-Translational Modification of Proteins

1.1 Identifying Translational Science within the Triangle of Biomedicine

1.2 State of Cardiology on Wall Stress, Ventricular Workload and Myocardial Contractile Reserve: Aspects of Translational Medicine (TM)

1.3 Risk of Bias in Translational Science

1.4 Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers

Chapter 2: Causes and the Etiology of Cardiovascular Diseases: Translational Approaches for Cardiothoracic Medicine

2.1 Genomics

2.1.1 Genomics-Based Classification

2.1.2  Targeting Untargetable Proto-Oncogenes

2.1.3  Searchable Genome for Drug Development

2.1.4 Zebrafish Study Tool

2.1.5  International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome.

2.2  Proteomics

2.2.1 The Role of Tight Junction Proteins in Water and Electrolyte Transport

2.2.2 Selective Ion Conduction

2.2.3 Translational Research on the Mechanism of Water and Electrolyte Movements into the Cell

2.2.4 Inhibition of the Cardiomyocyte-Specific Kinase TNNI3K ­ Oxidative Stress

2.2.5 Oxidized Calcium Calmodulin Kinase and Atrial Fibrillation

2.2.6 S-Nitrosylation in Cardiac Ischemia and Acute Coronary Syndrome

2.2.7 Acetylation and Deacetylation

2.2.8 Nitric Oxide Synthase Inhibitors (NOS-I) 

2.3 Cardiac and Vascular Signaling

2.3.1 The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets

2.3.2 Leptin Signaling in Mediating the Cardiac Hypertrophy associated with Obesity

2.3.3 Triggering of Plaque Disruption and Arterial Thrombosis

2.3.4 Sensors and Signaling in Oxidative Stress

2.3.5 Resistance to Receptor of Tyrosine Kinase

2.3.6  S-nitrosylation signaling in cell biology.

2.4  Platelet Endothelial Interaction

2.4.1 Platelets in Translational Research ­ 1

2.4.2 Platelets in Translational Research ­ 2: Discovery of Potential Anti-platelet Targets

2.4.3 The Final Considerations of the Role of Platelets and Platelet Endothelial Reactions in Atherosclerosis and Novel Treatments

2.4.4 Endothelial Function and Cardiovascular Disease
Larry H Bernstein, MD, FCAP

2.5 Post-translational modifications (PTMs)

2.5.1 Post-Translational Modifications

2.5.2.  Analysis of S-nitrosylated Proteins

2.5.3  Mechanisms of Disease: Signal Transduction: Akt Phosphorylates HK-II at Thr-473 and Increases Mitochondrial HK-II Association to Protect Cardiomyocytes

2.5.4  Acetylation and Deacetylation of non-Histone Proteins

2.5.5  Study Finds Low Methylation Regions Prone to Structural Mutation

2.6 Epigenetics and lncRNAs

2.6.1 The Magic of the Pandora’s Box : Epigenetics and Stemness with Long non-coding RNAs (lincRNA)

2.6.2 The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

2.6.3 Long Noncoding RNA Network regulates PTEN Transcription

2.6.4 How mobile elements in “Junk” DNA promote cancer. Part 1: Transposon-mediated tumorigenesis.

2.6.5 Transposon-mediated Gene Therapy improves Pulmonary Hemodynamics and attenuates Right Ventricular Hypertrophy: eNOS gene therapy reduces Pulmonary vascular remodeling and Arterial wall hyperplasia

2.6.6 Junk DNA codes for valuable miRNAs: non-coding DNA controls Diabetes

2.6.7 Targeted Nucleases

2.6.8 Late Onset of Alzheimer’s Disease and One-carbon Metabolism
Dr. Sudipta Saha

2.6.9 Amyloidosis with Cardiomyopathy

2.6.10 Long non-coding RNAs: Molecular Regulators of Cell Fate

2.7 Metabolomics

2.7.1 Expanding the Genetic Alphabet and Linking the Genome to the Metabolome

2.7.2 How Methionine Imbalance with Sulfur-Insufficiency Leads to Hyperhomocysteinemia

2.7.3 A Second Look at the Transthyretin Nutrition Inflammatory Conundrum

2.7.4 Transthyretin and Lean Body Mass in Stable and Stressed State

2.7.5 Hyperhomocysteinemia interaction with Protein C and Increased Thrombotic Risk

2.7.6 Telling NO to Cardiac Risk

2.8 Mitochondria and Oxidative Stress

2.8.1 Reversal of Cardiac Mitochondrial Dysfunction

2.8.2 Calcium Signaling, Cardiac Mitochondria and Metabolic Syndrome

2.8.3. Mitochondrial Dysfunction and Cardiac Disorders

2.8.4 Mitochondrial Metabolism and Cardiac Function

2.8.5 Mitochondria and Cardiovascular Disease: A Tribute to Richard Bing

2.8.6 MIT Scientists on Proteomics: All the Proteins in the Mitochondrial Matrix Identified

2.8.7 Mitochondrial Dynamics and Cardiovascular Diseases

2.8.8 Mitochondrial Damage and Repair under Oxidative Stress

2.8.9 Nitric Oxide has a Ubiquitous Role in the Regulation of Glycolysis -with a Concomitant Influence on Mitochondrial Function

2.8.10 Mitochondrial Mechanisms of Disease in Diabetes Mellitus

2.8.11 Mitochondria Dysfunction and Cardiovascular Disease – Mitochondria: More than just the “Powerhouse of the Cell”

Chapter 3: Risks and Biomarkers for Diagnosis and Prognosis in Translational Cardiothoracic Medicine

3.1 Biomarkers. Diagnosis and Management: Biomarkers. Present and Future.

3.2 Landscape of Cardiac Biomarkers for Improved Clinical Utilization

3.3 Achieving Automation in Serology: A New Frontier in Best

3.4 Accurate Identification and Treatment of Emergent Cardiac Events

3.5 Prognostic Marker Importance of Troponin I in Acute Decompensated Heart Failure (ADHF)

3.6 High-Sensitivity Cardiac Troponin Assays Preparing the United States for High-Sensitivity Cardiac Troponin Assays

3.7 Voices from the Cleveland Clinic On Circulating apoA1: A Biomarker for a Proatherogenic Process in the Artery Wall

3.8 Triggering of Plaque Disruption and Arterial Thrombosis

3.9 Relationship between Adiposity and High Fructose Intake Revealed

3.10 The Cardio-Renal Syndrome (CRS) in Heart Failure (HF)

3.11 Aneuploidy and Carcinogenesis

3.12 “Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US

Chapter 4: Therapeutic Aspects in Translational Cardiothoracic Medicine

4.1 Molecular and Cellular Cardiology

4.1.1 αllbβ3 Antagonists As An Example of Translational Medicine Therapeutics

4.1.2 Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function post MI

4.1.3 Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization

4.1.4 CELLWAVE Randomized Clinical Trial: Modest improvement in LVEF at 4 months ­ “Shock wave­facilitated intracoronary administration of BMCs” vs “Shock wave treatment alone”

4.1.5 Prostacyclin and Nitric Oxide: Adventures in vascular biology –  a tale of two mediators

4.1.6 Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmiasand Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy

4.1.7 Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

4.2 Interventional Cardiology and Cardiac Surgery – Mechanical Circulatory Support and Vascular Repair

4.2.1 Mechanical Circulatory Support System, LVAD, RVAD, Biventricular as a Bridge to Heart Transplantation or as “Destination Therapy”: Options for Patients in Advanced Heart Failure

4.2.2 Heart Transplantation: NHLBI’s Ten Year Strategic Research Plan to Achieving Evidence-based Outcomes

4.2.3 Improved Results for Treatment of Persistent type 2 Endoleak after Endovascular Aneurysm Repair: Onyx Glue Embolization

4.2.4 Carotid Endarterectomy (CEA) vs. Carotid Artery Stenting (CAS): Comparison of CMMS high-risk criteria on the Outcomes after Surgery: Analysis of the Society for Vascular Surgery (SVS) Vascular Registry Data

4.2.5 Effect of Hospital Characteristics on Outcomes of Endovascular Repair of Descending Aortic Aneurysms in US Medicare Population

4.2.6 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus

4.2.7 Preventive Medicine Philosophy: Excercise vs. Drug, IF More of the First THEN Less of the Second

4.2.8 Cardio-oncology and Onco-Cardiology Programs: Treatments for Cancer Patients with a History of Cardiovascular Disease

Summary to Part One

 

Part Two:

Cardiovascular Diseases and Regenerative Medicine

Introduction to Part Two

Chapter 1: Stem Cells in Cardiovascular Diseases

1.1 Regeneration: Cardiac System (cardiomyogenesis) and Vasculature (angiogenesis)

1.2 Notable Contributions to Regenerative Cardiology by Richard T. Lee (Lee’s Lab, Part I)

1.3 Contributions to Cardiomyocyte Interactions and Signaling (Lee’s Lab, Part II)

1.4 Jmjd3 and Cardiovascular Differentiation of Embryonic Stem Cells

1.5 Stem Cell Therapy for Coronary Artery Disease (CAD)

1.6 Intracoronary Transplantation of Progenitor Cells after Acute MI

1.7 Progenitor Cell Transplant for MI and Cardiogenesis (Part 1)

1.8 Source of Stem Cells to Ameliorate Damage Myocardium (Part 2)

1.9 Neoangiogenic Effect of Grafting an Acellular 3-Dimensional Collagen Scaffold Onto Myocardium (Part 3)

1.10 Transplantation of Modified Human Adipose Derived Stromal Cells Expressing VEGF165

1.11 Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function Post MI

Chapter 2: Regenerative Cell and Molecular Biology

2.1 Circulating Endothelial Progenitors Cells (cEPCs) as Biomarkers

2.2 Stem Cell Research — The Frontier at the Technion in Israel

2.3 Blood vessel-generating stem cells discovered

2.4 Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered

2.5 The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN

2.6 Innovations in Bio instrumentation for Measurement of Circulating Progenetor Endothelial Cells in Human Blood.

2.7 Endothelial Differentiation and Morphogenesis of Cardiac Precursor

Chapter 3: Therapeutics Levels In Molecular Cardiology

3.1 Secrets of Your Cells: Discovering Your Body’s Inner Intelligence (Sounds True, on sale May 1, 2013) by Sondra Barrett

3.2 Human Embryonic-Derived Cardiac Progenitor Cells for Myocardial Repair

3.3 Repair using iPPCs or Stem Cells

3.3.1 Reprogramming cell in Tissue Repair

3.3.2 Heart patients’ skin cells turned into healthy heart muscle cells

3.4 Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel 

3.5 Cardiovascular Outcomes: Function of circulating Endothelial Progenitor Cells (cEPCs): Exploring Pharmaco-therapy targeted at Endogenous Augmentation of cEPCs

3.6 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

Chapter 4: Research Proposals for Endogenous Augmentation of circulating Endothelial Progenitor Cells (cEPCs)

4.1 Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes

4.2 Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

4.3 Endothelin Receptors in Cardiovascular Diseases: The Role of eNOS Stimulation

4.4 Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

4.5 Positioning a Therapeutic Concept for Endogenous Augmentation of cEPCs — Therapeutic Indications for Macrovascular Disease: Coronary, Cerebrovascular and Peripheral

4.6 Endothelial Dysfunction, Diminished Availability of cEPCs, Increasing CVD Risk for Macrovascular Disease – Therapeutic Potential of cEPCs

4.7 Vascular Medicine and Biology: CLASSIFICATION OF FAST ACTING THERAPY FOR PATIENTS AT HIGH RISK FOR MACROVASCULAR EVENTS Macrovascular Disease – Therapeutic Potential of cEPCs

4.8 Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production

4.9 Resident-cell-based Therapy in Human Ischaemic Heart Disease: Evolution in the PROMISE of Thymosin beta4 for Cardiac Repair

4.10 Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

4.11 Bystolic’s generic Nebivolol – positive effect on circulating Endothelial Proginetor Cells endogenous augmentation

4.12 Heart Vasculature – Regeneration and Protection of Coronary Artery Endothelium and Smooth Muscle: A Concept-based Pharmacological Therapy of a Combination Three Drug Regimen including THYMOSIN

Summary to Part Two

Epilogue to Volume Four

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Agenda for Frontiers in Cancer Immunotherapy, February 27 – 28, 2017, The New York Academy of Sciences

Reporter: Aviva Lev-Ari, PhD, RN

 

  •  Frontiers in Cancer Immunotherapy

    February 27 – 28, 2017
    The New York Academy of Sciences

    Presented by The Mushett Family Foundation, Science, Science Immunology, Science Translational Medicine, and the New York Academy of Sciences

    Register Now

    Agenda

    * Presentation titles and times are subject to change.


    Day 1: February 27, 2017

    7:45 AM Breakfast and Registration
    8:30 AM Introduction and Welcome Remarks
    Representative, Mushett Family Foundation
    Representative, Science, Science Translational Medicine, and Science Immunology
    Representative, The New York Academy of Sciences
    8:55 AM Day 1 Keynote Address:
    Immune Checkpoint Blockade in Cancer Therapy: New Insights, Opportunities and Prospects for A Cure
    James P. Allison, PhD, The University of Texas MD Anderson Cancer Center

    Session 1: Assessment of Current Therapeutic Approaches in Cancer Immunotherapy: Successes and Challenges

    9:40 AM Title to Be Announced
    Phillip D. Greenberg, MD, University of Washington
    10:05 AM In situ Vaccination for the Treatment of Cancer
    Nina Bhardwaj, MD, PhD, Mount Sinai School of Medicine
    10:30 AM Treating the Tumor and Treating the Host
    Ronald Levy, MD, Stanford University
    10:55 AM Networking Coffee Break

    Session 2: Evaluation of Combination Therapy Strategies to Improve Clinical Outcomes

    11:25 AM Title to Be Announced
    Jedd D. Wolchok, MD, Memorial Sloan Kettering Cancer Center
    11:50 AM The Promise of Epigenetic Therapies for Enhancing the Efficacy of Immune Checkpoint Therapy
    Stephen B. Baylin, MD, Johns Hopkins University
    12:15 PM HPV Theraputic Vacccines: Where Are We Now and Where Are We Going?
    Cornelia (Connie) Liu Trimble, MD, Johns Hopkins University
    12:40 PM Networking Lunch and Poster Viewing
    12:55 PM Underrepresented Minorities, Women, and Early Career Investigator Career Development Workshop and Lunch Running Concurrently with the Networking Lunch

    For Graduate Students, Post-doctoral Fellows, and Junior Faculty

    Editor’s Guide to Writing and Publishing Your Paper

    Angela Colmone, PhD, Senior Editor, Science Translational Medicine
    Kristen Mueller, PhD, Senior Editor, Science
    Yevgeniya Nusinovich, MD, PhD, Associate Editor, Science Translational Medicine

    Session 3: Identification of Relevant Prognostic and Predictive Biomarkers for the Development of Immune-Monitoring Strategies

    2:00 PM Inflammation and Cancer: Fueling Response and Resistance of Immunotherapies
    Lisa Coussens, PhD, Oregon Health Sciences University
    2:25 PM High-throughput Single-Cell Analysis for T-Cell Receptor Ligands and Sequences
    Mark Davis, PhD, Stanford University
    2:50 PM Response and Resistance to PD-1 Blockade Therapy
    Antoni Ribas, MD, PhD, University of California Los Angeles
    3:15 PM Networking Coffee Break

    Session 4: Hot Topic Short Talks

    3:40 PM Short Talk Selected from Submitted Abstracts
    3:55 PM Short Talk Selected from Submitted Abstracts

    Session 5: Development of Strategies to Overcome Immune Tolerance

    4:10 PM Title to Be Announced
    Thomas Gajewski, MD, PhD, University of Chicago
    4:35 PM Molecular and Epigenetic Programs Underlying CD8 T Cell Dysfunction in Solid Tumors
    Andrea Schietinger, PhD, Memorial Sloan Kettering Cancer Center
    5:00 PM Targeting FoxP3+ T-cells in Cancers; Friends or Foes?
    Hiroyoshi Nishikawa, MD, PhD, National Cancer Center Hospital, Japan
    5:25 PM Panel Discussion
    5:50 PM Closing Remarks
    6:00 PM Poster Session 1 and Networking Reception
    7:00 PM Day 1 Adjourns

    Day 2: February 28, 2017

    8:00 AM Breakfast and Registration
    8:00 PM Underrepresented Minorities, Women, and Early Career Investigator Mentoring Breakfast Running Concurrently with the General Breakfast

    Session 6: Clinical Research Break Out Sessions

    9:00 AM Breakout Group 1: How to Manage Toxicities in Cancer Immunotherapy?
    Jedd D. Wolchok, MD, Memorial Sloan Kettering Cancer Center
    Breakout Group 2: How to Incorporate Biomarkers into Early Phase Immunotherapy Trials?
    Jonathan Cebon, MBBS, PhD, FRACP, Olivia Newton-John Cancer and Wellness Centre
    Breakout Group 3: What are the Latest Strategies for Cancer Immunotherapy Development — a Pharmaceutical Industry Perspective?
    Ira Mellman, PhD, Genentech
    10:00 AM Networking Coffee Break

    Session 7: Optimizing Incorporation of Cancer Genomics and Epigenomics into Immunotherapy Research and Clinical Strategies

    10:30 AM Title to Be Announced
    Steven Rosenberg, MD, PhD, National Cancer Institute, U.S. National Institutes of Health
    10:55 AM Title to Be Announced
    Michele Maio, MD, PhD, University Hospital, Sienna, Italy
    11:20 AM Using Cancer-specific Neoantigens to Personalize Cancer Immunotherapy
    Robert Schreiber, PhD, Washington University
    11:45 AM Networking Lunch and Poster Session 2

    Session 8: Targeting T-cells in Cancer Immunotherapy

    1:15 PM Regulatory T-cells and Strategies for Inhibition for Cancer Therapy
    Alexander Rudensky, PhD, Memorial Sloan Kettering Cancer Center
    1:40 PM Use of Engineered Chimeric Antigen Receptors for Leukemia Treatment
    Crystal Mackall, MD, Stanford University
    2:05 PM Title to Be Announced
    Kunle Odunsi, MD, PhD, Roswell Park Cancer Institute
    2:30 PM Networking Coffee Break

    Session 9: Hot Topic Short Talks

    3:00 PM Short Talk Selected from Submitted Abstracts
    3:15 PM Short Talk Selected from Submitted Abstracts

    Session 10: Emerging Technologies in Cancer Immunotherapy

    3:30 PM Title to Be Announced
    Laurence Zitvogel, MD, PhD, Institut National de la Santé et Recherche Médicale
    3:55 PM Emerging Technologies in Cancer Immunotherapy
    Carl June, MD, University of Pennsylvania
    4:20 PM Closing Remarks
    4:30 PM Conference Adjourns

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GE Healthcare has acquired Biosafe Group SA, a supplier of Integrated Cell Bioprocessing Systems for Cell Therapy and Regenerative Medicine Industry

Reporter: Aviva Lev-Ari, PhD, RN

 

CHALFONT ST GILES, England–(BUSINESS WIRE)–GE Healthcare has acquired Biosafe Group SA, a supplier of integrated cell bioprocessing systems for the rapidly growing cell therapy and regenerative medicine industry for an undisclosed sum. The acquisition of Biosafe expands GE Healthcare’s end-to-end ecosystem of products, solutions and services for our cell therapy customers, and expands GE’s technology reach to a number of new cell and therapy types.

“Together with GE we will have the combination of biological, engineering and industrial capabilities to help accelerate the fields of cell therapy and cellular immunotherapy into the mainstream, benefitting patients globally, and bringing the vision of personalized medicine to reality.”

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Cellular therapies are rapidly changing the healthcare landscape by providing life-saving and potentially curative treatments for many of the world’s most challenging diseases, especially cancer. The cell therapy oncology market alone is expected to reach $30 billion by 20301 with more than 600 potentially life-changing therapies in clinical trials at the end of 20152.

Biosafe, headquartered in the Lake Geneva region in Switzerland, with a global presence, has a 20 year track-record in automated cell processing and is a recognized leader in the field with reliable applications in bioprocessing, regenerative medicine and stem cell banking. Its proprietary products offer significant advantages over conventional processing tools, with closed fluid pathways, built-in traceability and single-use consumables. The strong strategic fit and complementary business models of GE Healthcare’s Life Sciences business and Biosafe combined with expanded capabilities in product development and commercial reach, will offer significant customer and ultimately patient benefits.

Kieran Murphy, CEO Life Sciences, GE Healthcare said: “GE is building a world-class set of tools, technologies and services for cell and gene therapy and Biosafe’s expertise and innovative systems will strongly enhance our customer offering. GE and Biosafe share a vision of an integrated approach to helping customers optimize every stage of their process to reduce production risks dramatically and increase access to these remarkable new medicines.”

Claude Fell, Founder and Chairman, Biosafe Group SA, said: “Together with GE we will have the combination of biological, engineering and industrial capabilities to help accelerate the fields of cell therapy and cellular immunotherapy into the mainstream, benefitting patients globally, and bringing the vision of personalized medicine to reality.” Olivier Waridel, Biosafe CEO, who will continue to lead Biosafe within the new integrated GEHC structure, added: “Joining GE Healthcare will give Biosafe an outstanding opportunity to couple its unique cell processing technology with GE Healthcare’s strong, global infrastructure, leading to improved capabilities for our customers and enhanced market penetration.”

GE’s strategy is to work with the industry and partners to develop a digitally-enabled ecosystem of complete tools, solutions and services for cell therapy aimed at accelerating the standardization, collaboration and integration customers need to bring these new therapies into mainstream clinical practice. GE has engaged globally with leaders in the industry, such as Canada’s Center for the Commercialization of Regenerative Medicine, the UK’s Cell and Gene Therapy Catapult, Australia’s Cell Therapy Manufacturing Cooperative Research Centre and leading clinical centers such as UPenn, Karolinska Institute, Memorial Sloan-Kettering and Mayo Clinic.

In 2016, GE has announced further significant investments in the cell therapy and regenerative medicine space. In April, GE Ventures and Mayo Clinic announced the launch of Vitruvian Networks, Inc., an independent platform company committed to accelerating access to cell and gene therapies through advanced, cloud-ready software systems and manufacturing services. In January, GE announced the BridGE@CCRM Cell Therapy Centre of Excellence, a US $31.5 million co-investment with the Canadian Government to promote new technologies for the production of cellular therapies in Toronto.

*END*

About GE Healthcare

GE Healthcare provides transformational medical technologies and services to meet the demand for increased access, enhanced quality and more affordable healthcare around the world. GE (NYSE: GE) works on things that matter – great people and technologies taking on tough challenges. From medical imaging, software & IT, patient monitoring and diagnostics to drug discovery, biopharmaceutical manufacturing technologies and performance improvement solutions, GE Healthcare helps medical professionals deliver great healthcare to their patients. For more information about GE Healthcare, visit our website atwww.gehealthcare.com.

About Biosafe Group SA

Founded in 1997 the Biosafe Group is active in the design, manufacture and marketing of automated cell processing systems. Headquartered in Switzerland and privately-owned, the Biosafe Group operates through regional subsidiaries (Geneva, Houston, Hong-Kong, Shanghai and São Paulo) and is present in more than 50 countries, either directly or through distributors. For more information about Biosafe, visit the website www.biosafe.ch.

1 http://www.centerwatch.com/news-online/2015/10/23/t-cell-immunotherapy-market-may-be-worth-30b-by-2030/

2 Alliance for Regenerative Medicine Q1 Data Report 2016 http://alliancerm.org/page/arm-data-reports#

GE to boost cell therapy tech with Biosafe acquisition

 

Biosafe has been working in the automated cell processing arena and offers proprietary products that include advantages–such as closed fluid pathways, built-in traceability and single-use consumables–over conventional tech.

“GE is building a world-class set of tools, technologies and services for cell and gene therapy and Biosafe’s expertise and innovative systems will strongly enhance our customer offering,” said Kieran Murphy, the CEO of life sciences at GE Healthcare. “GE and Biosafe share a vision of an integrated approach to helping customers optimize every stage of their process to reduce production risks dramatically and increase access to these remarkable new medicines.”

GE explained in the announcement that its strategy is to work with its partners on cell therapy, specifically looking to develop a digitally enabled offering of tools, solutions and services for cell therapy. The aim is to boost up standardization, collaboration and integration for customers so cell therapies can become mainstream in clinical practice, GE noted.

“Joining GE Healthcare will give Biosafe an outstanding opportunity to couple its unique cell processing technology with GE Healthcare’s strong, global infrastructure, leading to improved capabilities for our customers and enhanced market penetration,” said Biosafe CEO Olivier Waridel.

SOURCE

http://www.fiercebiotech.com/medical-devices/ge-to-boost-cell-therapy-tech-biosafe-group-sa-acquisition?utm_medium=nl&utm_source=internal&mrkid=993697&mkt_tok=eyJpIjoiWVdabE1EQXhaVEJrWkdaayIsInQiOiI1RzVJMFAwbFNxcCt1eFNhSktLQTZYTFhVUit4UlwvcnBFdFJYNlNvbWlNMG9UYUFJUUc0UmpPckJmS0ZoUXNYNUNScFJPQVwvQnpSY0hubjJxN1dkeDdENXprS0VWRDhtdEhHQlJBXC9JeE9Sdz0ifQ%3D%3D

 

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The Possibility of rejuvenating ageing bodies with injections of Blood Stem Cells saved from birth or early life: Free of Mutations and have Full-length Telomeres

Reporter: Aviva Lev-Ari, PhD, RN

 

 

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

  1. Henne Holstege1,10,
  2. Wayne Pfeiffer2,
  3. Daoud Sie3,
  4. Marc Hulsman4,
  5. Thomas J. Nicholas5,
  6. Clarence C. Lee6,
  7. Tristen Ross6,
  8. Jue Lin7,
  9. Mark A. Miller2,
  10. Bauke Ylstra3,
  11. Hanne Meijers-Heijboer1,
  12. Martijn H. Brugman8,
  13. Frank J.T. Staal8,
  14. Gert Holstege9,
  15. Marcel J.T. Reinders4,
  16. Timothy T. Harkins6,
  17. Samuel Levy5 and
  18. Erik A. Sistermans1

+Author Affiliations


  1. 1Department of Clinical Genetics, VU University Medical Center, 1007 MB Amsterdam, The Netherlands;

  2. 2San Diego Supercomputer Center, UCSD, La Jolla, California 92093, USA;

  3. 3Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands;

  4. 4Delft Bioinformatics Laboratory, Delft University of Technology, 2628 CD Delft, The Netherlands;

  5. 5Department of Molecular and Experimental Medicine, Scripps Translational Science Institute, San Diego, California 92037, USA;

  6. 6Advanced Applications Group, Life Technologies, Beverly, Massachusetts 01915, USA;

  7. 7Department of Biochemistry and Biophysics UCSF, San Francisco, California 94143, USA;

  8. 8Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;

  9. 9Centre for Clinical Research, University of Queensland, Herston, QLD 4006, Australia

Abstract

The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.

SOURCE

http://genome.cshlp.org/content/24/5/733

Blood of world’s oldest woman hints at limits of life

By Andy Coghlan

https://www.newscientist.com/article/dn25458-blood-of-worlds-oldest-woman-hints-at-limits-of-life

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