Stephen Holt MD-Recruiting Endogenous Stem Cells

8/8/2019 Stephen Holt MD-Recruiting Endogenous Stem Cells

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RECRUITING ENDOGENOUSRECRUITING ENDOGENOUS

ADULT STEM CELLS:ADULT STEM CELLS:THE BUILTTHE BUILT--IN REPAIR KITIN REPAIR KIT

Stephen Holt, MD, PhD, DSc, DNM, LLD et al.

Distinguished Professor of Medicine

(Emeritus)Scientific Advisor, Natural Clinician LLC



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

Two Principal Stem Cell TypesTwo Principal Stem Cell Types



Human Embryonic Stem CellsHuman Embryonic Stem Cells





Many Stem Cell TypesMany Stem Cell TypesReproduced from SA Biosciences, Pathways, 2009Reproduced from SA Biosciences, Pathways, 2009



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 distant widespread use



Adult Stem CellsAdult 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 thatinterfere with adhesion factors may

mobilize ASC.

Most information is known about HumanBone Marrow Adult Stem Cells.



Reproduced from Stem Cell Now, Scott CR, 2006



Reproduced from Stem Cell Now, Scott CR, 2006



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).



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



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).



PUSHING STEM CELLS TO DIFFERENTIATEPUSHING STEM CELLS TO DIFFERENTIATEReproduced from SABiosciences Inc, Pathways, 2009



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



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



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



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).



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

(UK vs. USA).



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.



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. beet root)

Spirulina, spinach, grape seed extract andAshwagandha provide antioxidant and cell

regulation potential



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 involves morethan just stem cell release, e.g. the benefits of cellular regulation, prodifferentiation etc.

Using AFA alone is not likely to be as effective assynergistic combinations.

Patent proposals on single or combined nutrientsand botanicals are superseded by more complex

synergistic formulations with greaterfunctionality. This is the expanded concept of stem cell support that I propose.



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.



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.



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 valuable approach in anti-aging

medicine.

While much further research on IASCR is

required, cumulative evidence to date

reinforces this promising approach for thepromotion of longevity, from one or more

perspectives.



CONCLUSIONSCONCLUSIONS

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.

Nutraceutical Stem Cell Support promises an

anti-aging revolution using novel and non-

invasive options, in an attempt to overcome

limitations of classic stem cell therapies.

Documents

Stephen Holt MD-Recruiting Endogenous Stem Cells