Transcript Signaling and Stem Cells nov 2011

Stem Cell Controversy
How Signaling Technology can
Benefit Stem Cell Therapies
By Xanya Sofra-Weiss, Ph.D
2006: Xia et al shows that cellular
proliferation increases with age,
whereas cellular differentiation
decreases with age. This finding is
correlated with an increase in tumors
with age (tumors are clusters of
undifferentiated cells) and may
represent one of the etiologies of
cancer.
SUCCESSFUL STEM CELL THERAPIES ARE BASED
ON SUCCESSFUL STEM CELL DIFFERENTIATION
2008: John Hopkins University Stem Cell
Research FOUND that blocking
potassium channels in ESCs slows their
growth and differentiation. Li et al, the
chief investigator at Hopkins Stem Cell
research, expresses concerns that
in humans with compromized ion
channels, and ESC that have failed to
differentiate, it is possible for stem cells
to form tumors and even initiate cancers.
What Happens During Aging?
The Role of Telomerase
Flores et al (2006)
Telomerase: The Stem Cell Factor
2006: Michael Clarke and Robert
Weingerg
postulate that at the heart of every tumor
lie a handful of aberrant stem cells that
maintain the malignant tissue. This is
the reason why tumors often regenerate
even after being almost destroyed by
anticancer drugs. Therefore anti-cancer
drugs should be selected for lethality to
cancer stem cells and not as the present
drugs kill any cells to shrink tumors.
2007: Brain tumor researchers have
found that brain tumors arise from
cancer stem cells living within tiny
protective areas formed by blood
vessels in the brain.
Killing those cells is a promising
strategy to eliminate tumors and
prevents them from re-growing.
2009: Lewis Wolpert in University
College London, in his book “How
we Live and Why we Die”, examines
the similarities between
stem cells and cancer such as their
“infinite capacity to divide”, the
tendency to not show decreased
division with aging as well as their
abundant telomerase.
Wopert (2009) discusses evidence
that stem cells are the driving force
in a tumors and claims that stem
cells are often the original source of
a tumor.
Most cancers arise from tissues that
contain dividing cells (eg skin, lung,
gut etc) For example nerves do not
divide so Brain cancers arise for
surrounding tissues and nerve stem
cells.
If Potassium Channels are
instrumental in Stem Cells
differentiation which is the
necessary process to avoid
tumors and cancers then we can
enhance Potassium Channels
with Electron Gated Signaling
Technology
Most Basic Mechanism of Signaling:
Electron Gated Ion Channels
The Electron’s electric
field amplifies the energy
of an Ion Channel by
increasing or decreasing
the height of the energy at
the gating cavity in this
Ion Channel at Energies
Below Thermal Noise
WHAT IS SIGNALING TECHNOLOGY?
Signaling Technology Amplifies or
substitutes cellular signaling that
occurs via proteins (antibodies,
hormones, enzymes, etc) signaling
that has diminished or paused with
age or disease
WHAT IS SIGNALING TECHNOLOGY?
Signaling Technology Amplifies or
substitutes cellular signaling that
occurs via proteins (antibodies,
hormones, enzymes, etc) signaling
that has diminished or paused with
age or disease
Aging and Disease
Aging is the result of deteriorated protein signals
leaving the body with multiple deficiencies in terms
of hormones, antibodies, enzymes and other proteins
such as collagen, elastin, hemoglobin, actin, myosin,
ATPace, etc
Cancer is not the result of a number of “rebel” cells
that refuse to follow the rules of cellular
proliferation and differentiation but a number of
“obedient” cells who got the wrong instructions as a
result of Singaling deficiency
2011: Proof that cancer is the result
of Cells getting the wrong signals
giving then the wrong instructions;
how do cells get the wrong
instructions?
Normally, cell division begins in
response to a signal received on the
cell's surface which tells the tightly
coiled DNA to unfold and copy itself.
How can the Wrong Instructions
Affect the Cell?
A single substitution an A for a G in a DNA molecule
can cause a signaling change in the conductance of
the molecule leading to cancer. Such research
findings demonstrate how the sequence of base pairs
in a DNA molecule can become determining factors
between health and disease, aging and youth.
2005- 2011: Stem Cells are
associated with the Wnt signaling
pathway which is a group of proteins
forming this signaling pathway.
Because Wnt signaling can act to
maintain stem cells as well as cancer
cells, the ability to modulate the Wnt
pathway either positively or
negatively may be of therapeutic
relevance.
Thus, utilizing Signaling
Technology to control activation of
Wnt signaling may allow us to
enhance stem cell and progenitor
cell activity, when regeneration is
needed. On the other hand,
inhibition of Wnt singalling may
prove to be an effective road to
inhibiting the uncontrolled renewal
that drives cancer.
A possible controlling agent of
stem cells that turned into
cancers is the P53 gene that
causes cell cycle arrest,
obstructing further division as
well as cell death by suicide.
Recent work has shown that
signaling the activation of P53 in
a tumor can halt the growth of a
tumor and often cause the tumor
2011: Howard Hughes Medical
Institute investigator Elaine Fuchs is
one of three scientists who have been
awarded the 2011 Albany Medical
Center Prize in Medicine and
Biomedical Research. Fuchs's
research has shown
that multiple signaling pathways,
including the Wnt and BMP pathways,
influence how stem cells are coaxed
to
2011: HMGB1 SIGNALING PATHWAY:
By tapping this signaling mechanism,
researchers could develop new
treatments for skin injuries like severe
burns. HMGB1 is like a “megaphone in
the system,” researchers said, putting
out a distress call
when stem cells are needed. Isolating
the signal HNGMB1 can solve a lot of
very serious medical conditions report
researchers from the King’s College
London and Osaka University, Japan
2011: We can induce
neuronal differentiation of
the neural stem cells,
a full-length coding region
of NeuroD, a neurogenic
transcription factor, must
be transfected into
HB1.F3 cells.
We are witnessing an explosion of
knowledge about signal transduction
pathways and how signaling pathways
affect healthy differentiation of stem
cells versus promoting cancers.
Signaling is now impacting virtually all
areas of biology and medicine and
more exact specifications are
identified by research daily.
How are these waveforms composed?
First we record the signals of interacting cells by cell recording methods
that focus on cellular interactions, using advanced computer software that
were developed specifically for that reason. Then we go through thousands
of combinations of signals to recompose the biological decoded signals
THE IMPORTANCE OF TIMING
Combining
the signals
is like editing
a movie
or composing
a symphony
Timing is
Crucial
Thank you