Stem Cell Technology Simplified

1. John Sanderson, MD
Topical Human Growth
Factors and Cytokines
in Skin Rejuvenation and
Procedure Recovery

2. RECOMMENDED TO OPTIMIZE AND STIMULATE SKIN HEALTH
HUMAN GROWTH FACTORS
& CYTOKINES GO MAINSTREAM

3. Guide you on a deep but brief dive
into the rapidly evolving science of
growth factors and stem cells as
applied to clinical aesthetics.
MY 20 MINUTE CHALLENGE:

4. The Evidence is UNDERWHELMING.
EFFICACY OF CURRENT GENERATION
OF TOPICAL ACTIVE INGREDIENTS

5. DERMATOLOGIC CONDITIONS REJUVENATION / AESTHETICS

6. THE NEW SCIENCE OF STEM
CELLS IS CHANGING EVERYTHING.

7. stem cells cytokines
growth factors
aesthetic modalities
regeneration
paracrine
autocrine
biosignals
rejuvenation
miRNA

8. WHAT ARE STEM CELLS?

9. Stem cells, cytokines & growth factors make life possible.
They control growth and development by regulating cell
division and differentiation. They orchestrate the healing
process of all injured tissues, including the skin.
FROM CONCEPTION ‘TIL DEATH…

10. • Signaling proteins
• Local and distant effects
• Circulate in picomolar quantities
• Peptides, proteins, glycoprotein,
• Picogram dose response curves
• Cellular communications
• Embryogenesis
• Immune function
Growth factors
are one of the
several classes of
cytokines.
Some cytokines are
pro-inflammatory.
Some cytokines are
anti-inflammatory.
WHAT ARE CYTOKINES?

11. • Cell-to-cell signaling molecules
• Alter gene expression
• Promote cell division – proliferation
• May inhibit apoptosis
• Morphogenesis
• Angiogenesis
• Cell differentiation – maturation
• Tissue homeostasis
• Wound healing
If unregulated –growth factors and
receptors implicated in cancers
WHAT ARE GROWTH FACTORS?

12. • Biosignaling
• Receptor
chemistry
• Highly
efficient
CELL TO CELL COMMUNICATION

13. One molecule -
chain reaction –
many cells
Don’t get with
your botanical
“actives”
Dosing advantage
for human GF’s!
PARACRINE AMPLIFICATION

14. 95% of the effect is
due to paracrine
chemical release
5% is due to
engraftment &
differentiation into
host tissue cell type
Conditioned medium
of culture of stem cells
equivalent effects
STEM CELL THERAPY

15. TGF-b1
TGF-b3
TGF-b2
Inflammatory - acute Inflammatory - chronic Growth factors- neutral Anti-inflammatory
Products with TGF-b1 create inflammation
- BUT inflammation is the enemy
Products that induce TGF-b1
e.g. “PLOD-2 gene” mimics
Products that just say TGF-b
Do they not know the difference?
The TGF-β Family of Growth Factors

16. CYTOKINES, GROWTH FACTORS AND HEALING

17. Don’t get
stuck here!
Optimal
aesthetic
outcomes
STAGES OF WOUND HEALING

18. COLLAGENESIS DURING WOUND HEALING

19. NATURE HEALS THEM …IN AN ORDERLY FASHION (BUT NOT ALWAYS)
DEVICES CREATE CONTROLLED WOUNDS

20. Major contributor to skin aging
& most skin maladies
Often responsible for
suboptimal outcomes in skin
rejuvenation and energy based
skin treatments
Positive aesthetic outcomes
can be enhanced/engineered
by controlling inflammation.
INFLAMMATION: THE PRIMARY CULPRIT
IN POOR AESTHETIC RESULTS

21. • During first and second trimesters, fetal
skin heals rapidly without scars.
• Inflammation is absent
or extremely brief.
• Anti-inflammatory
cytokines are abundant.
• During the third trimester, cutaneous
wounds heal more slowly, with
adult-like inflammation.
• Results in scars with over-production of
densely packed, disorganized collagen.
FETAL SKIN HEALS SCAR FREE

22. GOAL: EMULATE SCAR-FREE
FETAL WOUND HEALING

23. Inflammation is the major contributory
factor in hyperpigmentation and
hypopigmentation.
INFLAMMATION AND PIGMENTATION

24. Inflammation is the major contributory factor in fibrosis.
FIBROTIC ACNE SCARRING HYPERTROPHIC SCARS SCLERODERMA
COLLAGENESIS: DESIRED
FIBROSIS: DEFINITELY NOT

26. INFLAMMATION FIBROSIS CANCER

27. • Common aesthetic medical procedures involve the
delivery of energy or controlled trauma to the skin.
• The first phase of healing in response to any acute
insult is inflammation.
• The more swiftly the inflammatory phase can be
exited, and proliferation and remodeling phases
begin, the better the aesthetic result.
• Selection of appropriate topical growth factors and
cytokines can modulate and facilitate resolution of
inflammation.
MORE POSITIVE AESTHETIC OUTCOMES

28. Early
Evidence

29. WHAT ACTUALLY IS IN THESE
CONDITIONED MEDIA PRODUCTS?

30. • Reside in bone marrow
• Patrol the whole body
• Search out injury or distress
• Attach and set up shop
• Local drug store
• May engraft
• Sense requirements of healing
• Release cytokines & GF’s
• Orchestrates healing in stages
• When work is done – pulls out
• Returns to bone marrow
MESENCHYMAL STEM CELLS
OF BONE MARROW ORIGIN

31. • A special kind of adult stem cell controls
healing in all tissues, including the skin.
• They originate in the bone marrow and
patrol the body via the blood stream.
• Upon finding injury, they remain and act
as smart “mini-drugstores” secreting
cytokines and growth factors.
• This is the ONLY population of cells that
serves this function.
ONE POPULATION OF STEM
CELL CONTROLS TISSUE HEALING

32. “CONDUCTOR” OF
THE SYMPHONY
OF HEALING
“WORKER” IN TISSUE REPAIR
& RECONSTRUCTION
“FIREFIGHTER”
IN QUENCHING
INFLAMMATION
BONE MARROW STEM CELLS
PLAY MULTIPLE ROLES

33. • “Bone marrow-derived mesenchymal stem cells
have been shown to promote repair when applied
to cutaneous wounds.”
• “This study determined the effects of paracrine
signaling from bone marrow mesenchymal stem
cells on dermal fibroblasts included proliferation,
migration and expression of genes important in
wound repair.”
• “Bone marrow mesenchymal stem cells provide an
important early signal for dermal fibroblast
responses to cutaneous injury.”
Mesenchymal stem cells induce dermal fibroblast responses to injury
Experimental Cell Research Volume 316, Issue 1, 1 January 2010, Pages 48–54
FIBROBLASTS TAKE ORDERS, NOT GIVE THEM.

34. During cell culture, bone marrow
mesenchymal stem cells (MSC)
produce many fold the relative
concentration of growth factors and
cytokines important to the healing
process than do fibroblasts.
MESENCHYMAL STEM CELLS
VS. FIBROBLASTS

35. • Skin ages from accumulated damage
while cells tasked with repair decline.
• 4% remain at age 30.
• 2.5% at age 50
• Fewer cells means reduced pro-
healing anti-inflammatory bio-signals
Topical application of growth factors and cytokines produced in
cell cultures of BM-MSC is the physiologic equivalent of turning the
skin clock back to a younger time when there were more BM-MSC
circulating in the blood and resident within the skin.
BM-MSC NUMBER DECLINES WITH
AGE & SIGNALS SENESCENCE

36. Optimized for MSC growth & harvest
of pathway driven paracrine biosignals
We wrote the book
VENUS SKIN SCT

37. “…evidence shows that
administration of bone marrow stem
cell conditioned media, the broth the
cells were cultured in, produces the
same benefits as the cells themselves.
This is after all the cells are removed!
This supports the use of topical bio-signals from stem cells as a valuable topical
anti-aging technology. The effect of additional topical bio-signals is like having
more stem cells, like turning the skin clock back in time.
Bone Marrow Research Vol. 2011, Article ID 207326
KEY POINT

38. When applying
conditioned media
from cell cultures to
the skin, clinical
effects result from
the “net pattern” of
many growth
factors and
cytokines.
CYTOKINE & GF CLASSIFICATION

39. Bone marrow stem cell conditioned media
is markedly ANTI-INFLAMMATORY
BIO-SIGNAL PATTERN DETERMINES EFFECT.

40. • Niche is fixed in fact tissue
• Precursors to fat cells
• Create adipokines
(inflammatory)
• Grow very fast in culture
• Little or no cost
• By product of liposuction
• Average age adult 50’s
• Different secretome
• Pro-inflammatory balance
ADIPOSE DERIVED STEM CELLS

41. Adipose (fat) stem cell conditioned
media is highly PRO-INFLAMMATORY
BIO-SIGNAL PATTERN DETERMINES EFFECT.

42. The increased morbidity and mortality of obesity-associated cancers have been
attributed to higher levels of hormones, adipokines, and cytokines secreted by
the adipose tissue. The increased amount of adipose tissue also results in higher
numbers of adipose stromal/stem cells (ASCs). These ASCs have been shown to
impact cancer progression directly through several mechanisms, including the
increased recruitment of ASCs to the tumor site and increased production of
cytokines and growth factors by ASCs and other cells within the tumor stroma.
The obesity cancer paradigm: exploration of the interactions and crosstalk with adipose stem cells
Stem Cells 02/2015
Omental adipose tissue may play crucial roles for tumor promotion through the
expression of tumor promoting chemokines. Accordingly, tumor surrounding
adipose tissue may be a novel target for immunotherapy of cancer.
Adipose derived stem cell isolated from omentum: A novel source of chemokines for ovarian cancer growth
Journal of Caner Research and Therapeutics 01/2014
ADIPOSE STEM CELL CANCER CONCERNS

43. Our results demonstrated that BMSCs treatment caused
a delayed tumor growth and a prolonged survival in
both tumor models
[…] in vivo and in vitro results showed that BMSCs have
a systemic suppressive effect.
Bone marrow mesenchymal stem
cells suppress metastatic tumor
development in mouse by modulating
immune system.
Stem Cell Res Ther. 2015 Mar.

45. • Red face for decades with
flare ups TNTC
• Tx with daily doxycline,
topical metronidazole, and
steroid prn
• 7.1.2011 – all meds dc’d and
topical containing BM-MSC
CM started twice daily
• Reduced redness without a
flare up in > 4 years
PROOF OF CONCEPT IN PATIENT #1

46. Pilot trial:
24 days duration
Fourteen subjects (12f/1m)
36 to 72 yrs. of age
Measured:
Coarse lines, fine lines,
reflectivity, texture, tone,
coloration
Results:
All subjects improved in at
least one criterion.
11 of 14 (86%) observed
improvement in four criteria.
PILOT TRIAL BONE MARROW STEM CELL
CONDITIONED MEDIA

47. First generation bone marrow derived mesenchymal
stem cell conditioned medium as active
50 SUBJECT CLINICAL TRIAL

48. • Chronic red face for years
• Applied topical containing
BM-MSC CM twice daily
• Reduced redness and more even
skin tone at end of first month
REDUCED INFLAMMATION IN ONE MONTH

49. • Faster recovery
• Up to 40% less downtime
• Reduced inflammation
• Less edema
• Less discomfort
FACILITATED HEALING POST
FRACTIONAL CO2 LASER RESURFACING

50. • 10 p.m. – called saying “my face is on
fire. Do you think your product will
help?”
• Advised to take “before” photos and
immediately apply product containing
BM-MSC conditioned media.
• 7:30 a.m. – called saying “it was
amazing. My skin calmed very quickly.
When I woke up I had to call to let you
know.” Sent “after” photos taken
while still in her pajamas.
RESOLUTION OF INFLAMMATION
AFTER ERBIUM LASER

51. Four ablative treatments,
each a month part using a
BM-MSC cell culture
derived topical at time of
treatment, and another
formulated for twice daily
anti-aging skin care.
POST ABLATIVE RESULTS
ON A 74 YEAR OLD WOMAN

52. • Used product for 8 weeks
b.i.d.
• Two episodes of cosmetic
microneedling with .25 mm
device three weeks apart
RF ABLATIVE: ACNE & PIH

53. • Actually defensins – glycoproteins
snails secrete when stressed.
• Humans make their own defensins.
• Defensins are highly inflammatory.
• Snail antigens cross react with
house dust mite proteins IgE.
• Dust mites are one of the most
common human allergens.
• A case of allergic dermatitis in
context of using a snail “growth
factor” product as part of a
microneedling session
“GROWTH FACTORS” FROM SNAILS

54. • Take a culture of fibroblasts, add a substance,
then measure collagen
synthesis by cells.
• Simple minded logic: If it increases collagen
then it must be a growth factor.
• Truth: fibroblasts make collagen defensively.
You only need to perturb the cell a bit.
• Consequence: collagen made in the presence
of inflammation is gnarly, fibrotic, stiff, and
not aesthetically pleasing.
“GROWTH FACTORS” IN NAME ONLY

55. • Growth Factors (GF’s) & Cytokines are signaling molecules that
mediate human growth, healing and regeneration.
• Real human GF’s have real human growth factor receptors to match.
• They are 100% natural (to humans). Plant and animal GF’s are not
natural. Any salubrious effect is an accident of nature.
• Real human GF’s communicate in a paracrine fashion with signal
amplification in human tissues – a big deal in terms of dosing.
• Growth factors work in concert, not in isolation.
SUMMARY

56. • Stem cells make GF’s in abundance. 95% of the miracle of stem
cells is due to paracrine (chemical) effects.
• The stem cell secretome is different for each stem cell niche, and
can be coaxed to change under controlled lab conditions
• Bone marrow-derived stem cells are unique in that their whole
function is regenerative, not committed precursors to a single
tissue.
• They are recognized throughout regenerative medicine as the
master stem cells. When they are used up … end game.
SUMMARY

57. • Adipose stem cells have become a popular choice as paracrine
factories in aesthetics.
• Where inflammation is helpful in the short term, they are quite
valuable (orthopedics, fat transfers, etc.) In a single dose fashion.
• The presence of inflammation and potent adipokines like leptin
raises red flags about cancer risk.
• Recent literature abounds with examples.
SUMMARY

58. • The Venus Skin platform capitalizes on the advantages of
BM-MSC’s and adds an accumulated knowledge base of
stem cell secretomes.
• Custom cocktails means that specific skin conditions or
aesthetic concerns can be targeted.
• Anti-inflammatory GF admixtures can augment the effect of
various energy delivering modalities by employing specific
cocktails of growth factors matched to a specific clinical
effect
• Inflammation is not necessary for healing! It is something
that accompanies aging. But doesn’t have to.
SUMMARY