Stem Cell ControversyStem Cell ControversyHow Signaling Technology can How Signaling Technology can Benefit Stem Cell TherapiesBenefit Stem Cell Therapies

By Xanya Sofra-Weiss, Ph.DBy Xanya Sofra-Weiss, Ph.D

Stem Cell ControversyStem Cell ControversyHow Signaling Technology can How Signaling Technology can Benefit Stem Cell TherapiesBenefit Stem Cell Therapies

By Xanya Sofra-Weiss, Ph.DBy Xanya Sofra-Weiss, Ph.D

2006: Xia et al shows that cellular 2006: Xia et al shows that cellular proliferation increases with age, proliferation increases with age, whereas cellular differentiation whereas cellular differentiation decreases with age. This finding is decreases with age. This finding is correlated with an increase in correlated with an increase in tumors with age (tumors are clusters tumors with age (tumors are clusters of undifferentiated cells) and may of undifferentiated cells) and may represent one of the etiologies of represent one of the etiologies of cancer.cancer.

SUCCESSFUL STEM CELL THERAPIES ARE BASEDSUCCESSFUL STEM CELL THERAPIES ARE BASEDON SUCCESSFUL STEM CELL DIFFERENTIATIONON SUCCESSFUL STEM CELL DIFFERENTIATIONNOT SIMPLY CELLULAR PROLIFERATIONNOT SIMPLY CELLULAR PROLIFERATION

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 thatin 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

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

WHAT IS SIGNALING TECHNOLOGY?

Aging and Aging and DiseaseDisease

Aging is the result of deteriorated Aging is the result of deteriorated protein signals leaving the body with protein signals leaving the body with multiple deficiencies in terms of multiple deficiencies in terms of hormones, antibodies, enzymes and hormones, antibodies, enzymes and other proteins such as collagen, elastin, other proteins such as collagen, elastin, hemoglobin, actin, myosin, ATPace, etchemoglobin, actin, myosin, ATPace, etc

Cancer is not the result of a number of Cancer is not the result of a number of “rebel” cells that refuse to follow the “rebel” cells that refuse to follow the rules of cellular proliferation and rules of cellular proliferation and differentiation but a number of differentiation but a number of “obedient” cells who got the wrong “obedient” cells who got the wrong instructions as a result of Singaling instructions as a result of Singaling deficiencydeficiency

2011: Proof that cancer is the 2011: Proof that cancer is the result of Cells getting the result of Cells getting the wrong signals giving then the wrong signals giving then the wrong instructions; how do wrong instructions; how do cells get the wrong cells get the wrong instructions? instructions? Normally, cell division begins Normally, cell division begins in response to a signal in response to a signal received on the cell's surface received on the cell's surface which tells the tightly coiled which tells the tightly coiled DNA to unfold and copy itself. DNA to unfold and copy itself.

How can the Wrong Instructions How can the Wrong Instructions Affect the Cell?Affect the Cell?

A single substitution an A for a G in a DNA A single substitution an A for a G in a DNA molecule can cause a signaling change in the molecule can cause a signaling change in the conductance of the molecule leading to conductance of the molecule leading to cancer. Such research findings demonstrate cancer. Such research findings demonstrate how the sequence of base pairs in a DNA how the sequence of base pairs in a DNA molecule can become determining factors molecule can become determining factors between health and disease, aging and between health and disease, aging and youth.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 to disappear.

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 DIFFERENTIATE

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 callwhen 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 induceneuronal 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

Combining the signalsis like editing a movieor composing a symphony

Timing is Crucial

THE IMPORTANCE OF TIMING

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