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 cell
can form the
Embryo and placenta
This cell
can 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 Fields
Drs. 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: 0.128µW/g,
• Density of radio electric current flowing in the culture medium during the REAC
single radiofrequency burst (σ=1 A/V.m and ρ=1000Kg/m3
), J=30µA/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
Human Adult Stem Cells Were Exposed to REAC-

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
Gene Expression Analysis in Stem Cells Exposed to

Modulated Magnetic Field Exposure Triggers Expression of Cardiogenic Genes

Modulated Magnetic Field Exposure Triggers Genes Essential for
Neurogenesis and Skeletal Myogenesis
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
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 Times
By Nicolas Wade
Two 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 signals
1.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, Italy
Carlo Ventura
Silvia Cantoni
Francesca Bianchi
Claudia Cavallini
Margherita Galletti
Riccardo Tassinari
Elena Olivi
Irene Frascari
Rinaldi-Fontani Institute
Florence, Italy
Salvatore Rinaldi
Vania Fontani
Alessandro CastagnaI
Department of Biomedical Sciences,
University of Sassari, Italy
Margherita Maioli
Sara Santaniello
Gianfranco Pigliaru
Sara Gualini
NFN, Italy
Emilio Del Giudice
Alberto Tedeschi
Giuseppe Vitiello
Department of Chemistry
and Biochemistry
UCLA, LA, USA
James K. Gimzewski
Sarah Cross
Institute of HeartMath
Boulder Creek, CA, USA
Rollin McCraty
Prince Sultan Cardiac Center
Hofuf/Alahsa
Kingdom of Saudi Arabia
Abdullah Abdulrhman Alabdulgader
Cell Transplant Center
Diabetes Research Institute
(DRI) WorldWide DRI Federation
Miller School of Medicine
University of Miami, USA
Camillo Ricordi
Carlo Tremolada
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Dr. Carlo Ventura - DNA and Cell reprogramming

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