stephen holt md-stem cell summit mobilization
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STEM CELL MOBILIZATIONSTEM CELL MOBILIZATION
Stephen Holt, MD, PhD, DSc, DNM, LLD.
Distinguished Professor of Medicine
(Emeritus)
Scientific Advisor, Natural Clinician LLC
Board Member, European Society of
Antiaging Medicine
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CLASSIC EMBRYONIC STEM CELLS:
Pluripotent, found in the inner cell mass
of a preimplanted embryo (taboo) ADULT STEM CELLS:
Multipotent, found in undifferentiated
format, living in niches in adult tissuesand organs throughout the body
Two Principal Stem Cell TypesTwo Principal Stem Cell Types
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Human Embryonic Stem CellsHuman Embryonic Stem Cells
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Many Stem Cell TypesMany Stem Cell TypesReproduced from SA Biosciences, Pathways, 2009Reproduced from SA Biosciences, Pathways, 2009
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Stem Cell Therapies:Stem Cell Therapies:
Disadvantages and LimitationsDisadvantages and Limitations
Embryonic Stem Cells, Embryonic Germ Cells
and Fetal Tissue Stem Cells pose major ethical
and moral problems which cannot be resolved.
Cord Blood and Placental Stem Cells poseunresolved technical problems, e.g. survival.
Adult Stem Cells remain an imperfect
therapeutic procedure, except bone marrow.
Induced Pluripotent Stem Cells (Yamanaka,
2006) hold promise but widespread use distant
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Adult Stem CellsAdult Stem Cells
Adult Stem Cells (ASC) live in niches inmost organs and they can migrate.
They are tethered in niches by adhesion
molecules that determine cell migration
and niche retention. Compounds that
interfere with adhesion factors may
mobilize ASC.
Most information is known about Human
Bone Marrow Adult Stem Cells.
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A Novel and New Stem Cell Strategy inA Novel and New Stem Cell Strategy in
Integrative Medicine Practice: InducedIntegrative Medicine Practice: Induced
Adult Stem Cell Recruitment (IASCR)Adult Stem Cell Recruitment (IASCR)
Induced Adult Stem Cell technologies involvethe stimulation of endogenous stem cells to
regenerate or heal diseased or ailing tissues. Many compounds of natural or
pharmaceutical origin may play an active rolein the proliferation of human Adult Stem
Cells or cells carrying markers CD34+ andCD133+ (Jensen GS et al, 2002 and Bickford Pet al, 2006, Holt S, 2008).
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The Concepts of IASCR: Part 1The Concepts of IASCR: Part 1
Mobilize Adult Stem Cells from bonemarrow and other niche locations (?)
Increase circulation of ASC with a
semicontinuous, safe stimulus. Herbs,botanicals and nutrients are preferred to
drug approaches (cost, side effects)
Protect stem cells from oxidative damage
Encourage homing to desired target organ?
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The Concepts of IASCR: Part 2The Concepts of IASCR: Part 2
Assistance in the differentiation of Adult
Stem Cells to replace cell types of the
diseased organ has to be developed.
A body of research demonstrates that
human bone marrow Adult Stem Cells
are able to home in on diseased organs
and differentiate into many cell types
(Egletis, 1997 and Korbling et al, 2002).
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Factors that Mobilize Stem orFactors that Mobilize Stem or
Progenitor CellsProgenitor Cells
DRUGS (or isolated biologicals in clinical use
or trials): IL1, IL3, IL6, Stem Cell Factor (s),
erythropoetin, G-CSF etc.
NUTRACEUTICALS : oleic acid, linolenic acid,
blueberry, blue-green algae (AFA), green tea,
fucoidan and vitamin D3. Putative releasers or
antioxidant protection with fucoxanthin, beetroot, spirulina, spinach, ashwagandha, grape
seed extract. Cofactors Vit B12, Folate
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In Vitro Adult Stem Cell ReleaseIn Vitro Adult Stem Cell Release
by aby a LigandLigand for Human Lfor Human L--SelectinSelectin(Data from(Data from StemtechStemtech Inc. on AFA)Inc. on AFA)
AFA blocks L-Selectin, releasing Stem Cells
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In Vivo Release of ASCIn Vivo Release of ASC(Data from(Data from StemtechStemtech Inc. on AFA)Inc. on AFA)
AFA increases CD34+ Stem Cells (cf placebo)
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Fatty Acids Induce ASC ActivityFatty Acids Induce ASC Activity
Oleic and linolenic acids induce the
proliferation of human bone marrow stem
cells (Hisher et al, Blood, 1997, Stem Cells,
2002). Studies on Japanese herbal medicine(Kampo).
Oleic acid modulates the renewal of intestinalepithelial cells (Holehouse et al, 1998).
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Vitamin D3 Stimulates ProgenitorVitamin D3 Stimulates Progenitor
Stem CellsStem Cells
Mathieu et al (J.Steroid Biochem Mol
Biol, 2004) describe vitamin D and D3 as
causing proliferation of multipotent
progenitor cells.
Vitamin D deficiency is very common
and this is one key nutritional
mechanism of premature aging potential
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The Power of Synergy to PromoteThe Power of Synergy to Promote
Proliferation of Adult Stem CellsProliferation of Adult Stem Cells(Bickford et al, Stem Cells and Development, 2006)(Bickford et al, Stem Cells and Development, 2006)
A combination of blueberry and green tea
extracts with vitamin D3 and carnosine
promote the proliferation of bone marrow
progenitor cells (CD34+ and CD133+ cells).
Synergistic combinations of these botanicals
and nutrients resulted in a degree of stemcell proliferation that exceeded the ability of
human GM-CSF to induce this phenomenon.
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Miscellaneous Botanicals in IASCRMiscellaneous Botanicals in IASCR
Green tea contains polyphenols with anti-
aging, anti-cancer and cell protective benefits.
Blueberries contain compounds that
modulate cell signaling cascades with specificneuro-regenerative and protective effects
(ubiquitous anthocyanidins, e.g. beetroot)
Spirulina, spinach, grape seed extract andAshwagandha provide antioxidant and cell
regulatory potential
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Modern Formulations for StemModern Formulations for Stem
Cell Support or IASCRCell Support or IASCR
The power of synergy has emerged in theliterature and the process of IASCR whichinvolves more than just stem cell release, e.g. thebenefits of cellular regulation, differentiation etc.
Using AFA alone is not likely to be as effective assynergistic combinations. The Power of Synergy
Patent proposals on single or combined nutrientsand botanicals are superseded by more complexsynergistic formulations with greaterfunctionality. This is the expanded concept ofstem cell support that I propose.
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Proposed Formulations for StemProposed Formulations for Stem
Cell Support or IASCRCell Support or IASCR
Fatty acids: linolenic and oleic acid
Antioxidant protectors including anthocyanidins
(blueberry and beet root), spirulina, green tea
polyphenols, OPC and fucoxanthin
Key nutrient support with Vit D3 for cell
proliferation and nutritional support of bone
marrow function with Vit B12 and folate. Specific evidence-based stem cell releasers, e.g.
AFA, blueberry, Vit D3 and fucoidan are key.
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Unresolved Issues in IASCRUnresolved Issues in IASCR
Does Adult Stem Cell release and migration occurwith the proposed agents? YES
Does deployment of ASC occur to the target
organs in a reproducible manner? PROBABLY YES Does engagement and recruitment with
proliferation of endogenous stem cells occur?
PROBABLY YES
Is there a rational basis to use this natural
approach? YES, the proposed agents have multi-
functional benefits, independent of mobilization
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Placing IASCR into a TherapeuticPlacing IASCR into a Therapeutic
PerspectivePerspective
The administration of safe natural agents
with stem cell releasing or protecting
qualities is a novel approach in treatment of
chronic disease and anti-aging medicine.
While much further research on IASCR is
required, cumulative evidence to date
reinforces this promising approach fordisease management and the promotion of
longevity, from one or more perspectives.
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CONCLUSIONSCONCLUSIONS
A decade of research on the use ofpharmaceutical or natural compounds torecruit endogenous ASC has accelerated.
The concept of IASCR with nutraceutical STEM
CELL SUPPORT appears feasible and applicable,but more research is required.
Nutraceutical Stem Cell Support promises ananti-aging revolution using novel and non-invasive options, in an attempt to overcomesome limitations of existing stem celltherapies.