STEM 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
 Two Principal Stem Cell
Types
• 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 tissues
and organs throughout the body
Human Embryonic Stem Cells
 Many Stem Cell Types
Reproduced from SA Biosciences, Pathways, 2009
 Stem Cell Therapies:
Disadvantages 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 pose
unresolved 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
 Adult Stem Cells
• Adult Stem Cells (ASC) live in niches in
most 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.
 A Novel and New Stem Cell Strategy in
Integrative Medicine Practice: Induced
Adult Stem Cell Recruitment (IASCR)
• Induced Adult Stem Cell technologies involve
the stimulation of endogenous stem cells to
regenerate or heal diseased or ailing tissues.
• Many compounds of natural or
pharmaceutical origin may play an active
role in the proliferation of human Adult Stem
Cells or cells carrying markers CD34+ and
CD133+ (Jensen GS et al, 2002 and Bickford P
et al, 2006, Holt S, 2008).
 The Concepts of IASCR: Part 1
• Mobilize Adult Stem Cells from bone
marrow 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?
The 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).
 Factors that Mobilize Stem or
Progenitor 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,
beet root, spirulina, spinach, ashwagandha,
grape seed extract. Cofactors Vit B12, Folate
 In Vitro Adult Stem Cell Release
by a Ligand for Human L-Selectin
(Data from Stemtech Inc. on AFA)

AFA blocks L-Selectin, releasing Stem Cells

 In Vivo Release of ASC
(Data from Stemtech Inc. on AFA)

AFA increases CD34+ Stem Cells (cf placebo)

 Fatty 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 intestinal

epithelial cells (Holehouse et al, 1998).
 Vitamin D3 Stimulates Progenitor
Stem 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
 The Power of Synergy to Promote
Proliferation of Adult Stem Cells
(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 stem
cell proliferation that exceeded the ability of
human GM-CSF to induce this phenomenon.
 Miscellaneous 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 specific
neuro-regenerative and protective effects
(ubiquitous anthocyanidins, e.g. beetroot)
• Spirulina, spinach, grape seed extract and
Ashwagandha provide antioxidant and cell
regulatory potential
 Modern Formulations for Stem
Cell Support or IASCR
• The power of synergy has emerged in the
literature and the process of IASCR which
involves more than just stem cell release, e.g.
the benefits of cellular regulation, differentiation
etc.
• Using AFA alone is not likely to be as effective as
synergistic combinations. The Power of Synergy©
• Patent proposals on single or combined
nutrients and botanicals are superseded by more
complex synergistic formulations with greater
functionality. This is the expanded concept of
stem cell support that I propose.
 Proposed Formulations for Stem
Cell 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.
 Unresolved Issues in IASCR
• Does Adult Stem Cell release and migration occur
with 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
 Placing IASCR into a Therapeutic
Perspective
• 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 for
disease management and the promotion of
longevity, from one or more perspectives.
 CONCLUSIONS
• A decade of research on the use of
pharmaceutical or natural compounds to
recruit 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 an
anti-aging revolution using novel and non-
invasive options, in an attempt to overcome
some limitations of existing stem cell
therapies.