dr. carlo ventura - dna and cell reprogramming

Connecting Hearts and Minds

DNA and Cell Reprogramming via Epigenetic Information ©2013 Visual Institute of Developmental Science

DNA and Cell Reprogramming via Epigenetic Information Delivered by Magnetic Fields, Sound Vibrations,

and Coherent Water

Carlo Ventura, MD, Ph.D.Full Professor of Molecular Biology

University of Bologna, Italy

VID (Visual Institute of Developmental Sciences) Laboratory of Molecular Biology and Stem Cell Engineering, NIBB , Bologna, Italy

Experimental Cardiology at the Cardiovascular Department, University of Bologna, Italy



This cellcan form the

Embryo and placenta

This cellcan just form

the embryo

Fully mature

Toti-potent

Pluri-potent

Multi-potent

Stem Cells and Regenerative Medicine



NOT ONLY MOLECULES!BUT…

Turning on stem cell cardio-genesis with extremely low frequency magnetic fields



Turning on Stem Cell Cardiogenesis with Extremely Low Frequency Magnetic Fields

Ventura C et al. FASEB J 2004

Sinusoidal Magnetic Field (MF)(50 Hz, 0.8 mTrms)

Genes that Trigger Cardiac Cell Commitment Increases Cardiac Specific Genes and Proteins



Dynorphin B (Natural Chemistry) Magnetic Fields (Magnetic Waves)

Spontaneously Beating Cardiomyocytes Appearing After Treatment of Mouse Embryonic Stem Cells with:



Magnetic fields in the Wi-Fi band of 2.4 GHz, the same used with wireless Internet connections worldwide, were used with an innovative device, called the Radio Electric Asymmetric Conveyer (REAC), to modulate the ability of stem cells to differentiate or even make adult non-stem cells behave like stem cells.

The REAC technology is based upon the interaction of two oscillating magnetic fields. One is generated by cells or the entire organism, and the other is a weaker electromagnetic field produced by the REAC system. A resultant electromagnetic field induces the cells to respond with endogenous self-generated micro-currents, likely ensuing from cellular ionic fluxes. These currents are detected and conveyed back to the cells with a conveyer probe.

Magnetic Energy: A Tool for Modulation of Cell Signaling and Fate



REAC - Modulated Magnetic FieldsDrs. Salvatore Rinaldi and Vania Fontani

Radiofrequency generators and irradiating antennas (1) create a 2.4 GHz radiofrequency field; electrodes (2) connected through a cable (CV). The radio frequency field induces radiofrequency currents in the body, which are detected and conveyed back by the electrodes.

The REAC apparatus adapted to an embryonic stem cell culture system within a CO2 incubator.



Distance between the RF emitter and the culture medium is approximately 35 cm.Electromagnetic quantities (detected by receiving antenna and spectrum analyser; single radiofrequency bursts of 250 ms. with an off interval of 2.5 seconds):

• Radiated power: 2 mW,• Electric field: 0.4 V/m,• Magnetic field: 1mA/m,• Specific Absorption Rate – SAR: 0.128W/g,• Density of radio electric current flowing in the culture medium during the REAC

single radiofrequency burst (=1 A/V.m and =1000Kg/m3), J=30A/cm2.• Specific power: around 400 μW/m²

EXPOSURE CONDITIONS

With REAC Without REAC

Embryod Bodies2 days in suspension

Undifferentiated Cells

Additional 7 days in tissue culture



Radiofrequency Energy Loop Primes Cardiac, Neuronal, and Skeletal Muscle Differentiation in Mouse Embryonic Stem Cells:A New Tool for Improving Tissue Regeneration



Modulated Magnetic Fields Primes the Expression of Genes Driving Cardiac, Neuronal and Skeletal Muscle Differentiation

Cardiac Driving Genes

Muscle Gene Neuron Gene



Embryonic stem cell exposure to modulated magnetic fields affects the expression of stem cell related proteins and optimizes expression of pluripotent cells.

Cardiac Proteins Neural Proteins



Control REAC

Modulated magnetic fields enhances the yield of embryonic stem cell derived cardio-myocytes and affects the quality of beating and contractile dynamics.

REAC Treated



Human Adult Stem Cells Were Exposed to REAC-Modulated Magnetic Fields



Fat tissue aspirates are processed in a non-enzymatic fashion through a new technology (Lipogems) to harvest stem cells.

Filling with PBSl

Filling with

lipoaspiratel

Washing/Emulsion

Expulsion of Lipogem product



Morphological Appearance of Stem Cells

Day 3 Day 4

Day 6 Day 12



Gene Expression Analysis in Stem Cells Exposed to Modulated Magnetic Fields



Modulated Magnetic Field Exposure Triggers Expression of Cardiogenic Genes



Modulated Magnetic Field Exposure Triggers Genes Essential for Neurogenesis and Skeletal Myogenesis



Confocal Microscopy Analysis of the Effect of Modulated Magnetic Fields on the Expression of Selected

Marker Proteins in Human Adult (Adipose-Derived) Stem Cells



Magnetic Fileds Drive Human (Adipose-Derived) Stem Cell Differentiation



The 2012 Nobel Prize in Physiology or Medicine: for the discovery that mature cells can be reprogrammed to become pluripotent.

The New York TimesBy Nicolas WadeTwo scientists who were awarded the Nobel Prize in Physiology or Medicine on Monday helped lay the foundation for regenerative medicine, the hotly pursued though still distant idea of rebuilding the body with tissues generated from its own cells. They are John B. Gurdon of the University of Cambridge in England and Shinya Yamanaka of Kyoto University in Japan.Both men had to overcome false starts in life. Dr. Gurdon was told as a boy that he was wholly unsuited for biology, and Dr. Yamanaka trained as a surgeon only to find he was not so good at it.

Dr. Yamanaka Dr. Gurdon



Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors



Modulated Magnetic Field Exposure Does Not Affect Cell Viability



Mef2c Tbx5 Gene

GATA4 Gene

Modulated Magnetic Fields Can Drive Human Fibroblasts into Cardiac Gene Reprogramming

Mef2c Gene



Modulated Magnetic Fields elicits the expression of genes orchestrating human fibroblast commitment towards cardiogenic,

skeletal myogenic and neurogenic lineages.Prodynorphin Gene Nkx2.5 Gene

Neurogenin1 Gene MyoD Gene



cMyc GeneSox2 Gene Oct4 Gene

Nanog Gene Klf4 Gene

Modulated magnetic field treatment time-dependently modulates the expression of genes involved in fibroblast

reprogramming into pluripotent cells.



Cardiac Cells Skeletal Muscle Cells Neural Cells

Modulated Magnetic Fields Primes Human Fibroblast Differentiation

into Lineages in which Cells Would Never Otherwise Appear



Cell Reprogramming with

Sound Vibration



Extracellular and Intracellular Environments:A World of Continuous Vibrations



Atomic Force Microscopy to Detect Cellular Nano-mechanical Vibrational Patterns



22 °C

26 °C

30 °C

Dead cell

Atomic Force Microscopy of Nano-mechanical Signatures During Stem Cell Development

“Nano-mechanical characterization of cellular activity – Sonocytology”

Carlo Ventura (NIBB-VID) & James K. Gimzewski (UCLA)

With Mike Horton–UCLA, Mark Welland and members of Dept. of Chemistry, Terry McMaster-Bristol, Daniel Roberts-Bristol,

Henrich Horber–UCLA, Quentin Pankhurst–UCLA, Andrew Fisher–UCLA

Sound from single yeast cell



Atomic Force Microscopy and Nano-mechanical Probing:Transcription Factor Dynamics of DNA



General Transcriptional Machinery



Water can be “Signalized” Non-Locally with Biological Information to Generate Coherent Domains Capable of

Quantum Signaling and Information Transfer

Developments in Implicit Computational Complexity



Crucial Experimental Details:•Filtration: 450/100 nm for bacterial DNA, 450/20 nm for viral DNA.•High dilutions in water.•Mechanical agitation (vortex) between each dilution.•Excitation by the electromagnetic background of extremely low frequency, starting at 7 Hz. •The excitation is not induced when the system is shielded by a mu-metal cage.

Typical signals from aqueous dilutions of M. Pyrum. Positive signals from D-7 to D-12 dilutions.

Device for the capture and analysis of EM signals1.Coil made up of copper wire, impedance 300 Ohms.2.Plastic tube containing 1ml of the solution to be analyzed. 3.Amplifier. The solution contained viral or bacterial DNA Fragments.



LTR HIV DNA Fragment

Transmission of DNA Information into Water Through Electromagnetic Waves

DNA with 98% sequence identical to the original DNA sequence.

Water nanostructures and their electromagnetic resonance can faithfully maintain DNA information.

Nucleotides, primers, polymerase amplification



Information is thought to be the essence of life, as in the DNA code. We have growing needs of separating the “informational content” of life

from its “material substrate.”

In both the philosophical and visual sense, ‘seeing is believing’ does not apply to nano-technology, for there is nothing even remotely visible. On the atomic and molecular scale, data is recorded by sensing and probing in a very abstract manner, which requires complex and approximate interpretations. More than in any other science, visualization and creation of a narrative becomes necessary to describe what is sensed, not seen.



NIBB - VID Laboratory of Molecular Biology and Stem Cell Engineering Bologna, ItalyCarlo Ventura Silvia Cantoni Francesca Bianchi Claudia CavalliniMargherita Galletti Riccardo TassinariElena OliviIrene Frascari

Rinaldi-Fontani Institute Florence, ItalySalvatore RinaldiVania FontaniAlessandro CastagnaI

Department of Biomedical Sciences, University of Sassari, ItalyMargherita MaioliSara SantanielloGianfranco PigliaruSara Gualini

NFN, ItalyEmilio Del GiudiceAlberto TedeschiGiuseppe Vitiello

Department of Chemistry and BiochemistryUCLA, LA, USAJames K. GimzewskiSarah Cross

Institute of HeartMathBoulder Creek, CA, USARollin McCraty

Prince Sultan Cardiac CenterHofuf/AlahsaKingdom of Saudi ArabiaAbdullah Abdulrhman Alabdulgader

Cell Transplant CenterDiabetes Research Institute (DRI) WorldWide DRI FederationMiller School of MedicineUniversity of Miami, USACamillo RicordiCarlo Tremolada

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