Transcript nanofactor flow - Dr. Phil Davidson

An Alternative in Managing Knee Arthritis
Phil Davidson, MD
Park City, UT
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NSAIDS
PT
Weight loss
Bracing
Injection Therapy
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Corticosteroids
Viscosupplementation
PRP
Autologous MSC’s (BMA derived)
Amniotic Tissue Graft-Allogeneic MSC
 Corticosteroids-good
and bad….
 Viscosupplementation:
unpredictable, often ineffective,
only potential to address aching,
no reparative capacity, many
insurances are not authorizing
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Rapidly reduce pain due to inflammation
Last for several weeks to months
Joints, Spine radiculopathy, Bursitis, Tendonitis, Neural
inflammation (CTS)
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Atrophy
Depigmentation
Hyperglycemia
Infection
Post injection flare
Tissue structure weakening, tendon ruptures
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Chondrocytes and MSCs exposed to PRP show
increased cell proliferation and cartilage extracellular matrix synthesis of PG and Type II
collagen
Synoviocytes cultured in PRP produce more HAbetter lubrication and chondroprotective?
Better pain scale outcomes with PRP injections
versus HA injections for management of knee
OA
PRP preps highly variable
Over 6000 articles on PRP/only 50% of them
show an effect-platelets, leucocytes?
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Biologic treatment is interactive
KEY ELEMENTS ALL REQUIRED:
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A “Nutrient Rich Soup” includes-
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Potential sources of this “Soup”:
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◦ Growth factors, cells, scaffold
◦ Mechanically favorable environment
◦ Cells (RBC, white cells, MSC)
◦ Growth factors (from platelets or plasma)
◦ Scaffolds
◦ Bone Marrow Aspirate, Amniotic Fluid
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MSC’s are undifferentiated cells:
◦ Capacity for prolonged self-renewal
◦ Ability to differentiate into specialized cell types
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Have shown enhanced cartilage, tendon and
meniscus healing
These results have increased patient awareness
and demand
High-profile professional athletes are signing up
for relatively untested cell-based therapies
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Attractive to patients-they want regeneration
technology rather than replacement
Harness your own body’s ability to heal
Not taking exogenous drugs
You are using your cells to heal your tissues
Perception that stem cells are reversing the
trend not just treating it
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MSCs do not recreate tissue
Modify the environment to enhance healing
Patients feel better-anti-inflammatory effect
May have role for Osteoarthritis
May be a role for augmenting surgical
procedures-ACLR, RCR, cartilage restoration
We don’t know the ideal type or number of
stem cells in specific indications
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Increased meniscal volume in postmenisectomy patients who received adult
MSC injections into the knee
MSC implanted for knee OA showed improved
activity levels and cartilage regeneration
One-step MSC treatment for large full
thickness chondral defects showed
improvement and significant cartilage fill
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Current MSC treatments for OA include BMA
derived autogenous stem cells that are
immediately injected into the knee
Jim Andrews MD at the Andrews Institute believes
it controls swelling and inflammation and eases
pain in knee OA
Results in a pilot study of 31 NFL players, at 10
months, showed efficacy
Reported decreased pain up to 45% with scores &
improved by 50% from baseline at 6 months
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So why use nanofactor FLOW if BMA works?
Growth factors, scaffolding, and MSCs
First used in 1910
Preservation techniques in 1940
Has been proven in ophthalmology, burns, plastic
surgery, foot and ankle, diabetic ulcers
Amniotic fluid stem cells have a delayed/more
robust differentiation compared to bonemarrow
derived MSC in recent studies
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Journal Transplantation, April 2015
Prospective Randomized Trial for Knee OA
Allograft MSC vs Hyaluronic Acid injected in knee
One year follow up
MSC patients improved clinical outcomes,
including pain vs. HA
MSC patients showed actual IMPROVEMENT in
cartilage quality and quantity on MRI vs. HA
Attributes of Amniotic Tissue
• Immunoprivileged (no class 1 or 2 HLA antigens)
– No rejection reaction
• Anti Inflammatory
• Transforming growth factor beta-1 (TGF-1)
• Insulin-like growth factor I (IGF-I)
• Anti Microbial- defensing/peptides/ enzymes
• Cells: MSC’s, Fibroblasts and Keratinocytes +++
Chen EH, et al. J Implant Adv Clin Dent. 2009;2(3):67-75.
(2)Bongiovanni cd133+ cell as advanced medicinal product
for Myocardial and limb ischemia
Stem cells and development vol23, 20, 2014
(3)Karantalis, MSc w CABG circulation research Feb 2014
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900,000 cells/mL
44% MSC’s; remainder-kerintinocytes,
fibroblasts, epidermal
Collagen Types III, IV, V, VII
Amino acid precursors – taurine, glutamine
Growth factors: Epidermal growth factor,
Transforming growth factor alpha & beta-1,
Insulin-like growth factor 1, Granulocyte colony
stimulating factor
(AmnioTechnology LLC, with permission)
Nanofactor Flow:
MSCs + Growth Factors + Scaffold
Nanofactor Membrane:
NanoFx (MSCs) + Growth Factors + Scaffold
PRP
1 Element Tx
BMA
2 Element Tx
Nanofactor
All Elements
Amniotic Membrane
Amniotic Scaffolding
Cryofractured Amnion
Membrane
particle
Scanning Electron Microscopic image of cryofractured amniotic membrane
particles.
Nanofactor
Minimally Manipulated Extracellular Matrix
Morcelized Tissue
Disrupted 3D Structure
CryoFractured Tissue
Intact 3D Structure
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Growth factors
Scaffolding
Cells and lots of them and immature-pluripotential-900,000 viable cells/ml, 44% are
MSCs in one ml
BMA has 1,500 CFU-f/ml, another article
stating 2,300 CFU-f/ml (donors<1 yo) to 500
CFU-f/ml (donors>60)
BMA cells are senile
Amniotic
440,000 MSC’s/1ml
Bone Marrow Aspirate
1,600 MSC’s/1ml
Jing Li et al: Chin J Cancer Res 23(1): 43-48, 2011
MSCs per Marrow Cells
Human MSCs Decline with Age
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1,000
Estimates
obtained by
CFU- f assay
Newborn
1
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100,000
1
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250,000
Teen
30
Age (Years)
Adopted from: Al Caplan. J Pathol 2009; 217:318-314, 2008
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400,000
1
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2,000,000
50
80
Relative Number of MSC’s by Age
MSCs per Marrow Cells
Adopted from: Al Caplan. J Pathol 2009; 217:318-314, 2008
2000
400
Newborn
Teen
Age (Years)
250
30
100
50
1
80
Amniotic Tissue Allograft
Nanofactor FLOW
Cellular
Growth
Factors/Peptides + Components
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Extracellular
Matrix
Amniotic Placental Tissue
Collection
Scheduled c-section
- Amniotic fluid (~ 650cc)
Overnight at 1-10o
- Amnion membrane (900 cm2)
C
Consent
Infectious Disease Testing
Shipping to Manufacturing Facility
Tissue Processing
3-4
weeks
Final Product Lot Release
Processed in Class ISO 5
Bioburden Testing USP <61>
Environmental Monitoring
Micronized Amnion
Growth Factors, Cytokines, ECM
Proteins
Viable Cells
5% DMSO
Sterility Testing USP <71>
Mycoplasma Testing USP <63>
Endotoxin Testing USP < 85>
Product Packaging and Distribution >65o C
How do the sources compare?
“A multipotent stem
cell population that
is still of fetal origin
and may be superior
in proliferation and
differentiation to
cells deriving from
adult tissues”
Francesco Alviano et al,
BMC Developmental Biology
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Patients can benefit from this non surgical
treatement modality
Many patients want/need to avoid surgery
Large demographic of patients wants to “try
everything before considering surgery”
This is only modality that has the actual ability
heal cartilage and tissues (vs steroid/HA)
Easier to administer than PRP/BMA
Cost is not out of line with PRP/BMA
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Attractive option to include “stem cells”
Safe, no rejection, no after-pain
New technology without specific indication
parameters
I discuss the concept of orthobiologic treatment to
include the 3 key elements: cells, growth factors and
scaffolding
I explain that senescent MSC’s make very little sense
to me
It is not a magic bullet but it does have promise
I explain that it is expensive and not covered by
insurance
PHASE I
Getting Started in the Office
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CryoFreezer:
If you plan to do any
volume
Dilutants &
Nanofactor
Flow
Acceptable Dilutants
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(Pure) Lidocaine /Marcaine, (not in joints)
PRP (Platelet Rich Plasma):
PPP (Platelet Poor Plasma):
Hyaluronic acid (supartz, eufflexa):
Saline: Use Normal Saline:
– Types of Saline:
• Normal: Sterile Solution of Sodium chloride in water
• Bacteriostatic: Sterile Solution with 0.9% benzyl
alcohol with no sodium chloride
Flow
Unacceptable Dilutants
• Do Not Use
– Glycerol (eg. Grafton DBM)
– Glucose Solutions (eg. D5NS)
– Epinephrine (in or around treatment site)
– Lidocaine/ Marcaine (with preservative) in joints
• Do NOT Use Systemically – no IV or intra arterial injections
• No literature to support this method of administration.
Flow
Preparation & Mixing
1. Remove the package from freezer or dry
ice container. Cut the package. *Outside of
vial is not sterile
1. Defrost vial by holding still in hand for 3-5
minutes. *Do not shake vial
1. Fill syringe with dilutant. (typically 1:1
ratio)
1. Draw Nanofactor™ Flow into syringe with
18g needle.
1. Use a 22 or 23g needle for injection but
nothing smaller than a 23g
Flow
Recommended Joint Dosing
Shoulder
1ml Flow Graft,
1:2 up to 1:4 dilution
Hip
2ml Flow Graft,
1:2 up to 1:3 dilution
Elbow
1ml Flow Graft,
1:1 dilution
Knee
(per compartment)
Stage 3: 0.5ml Flow Graft,
Stage 4: 1ml Flow Graft,
1:2 dilution
Wrist, Fingers & Facets
(per joint)
0.25ml Flow Graft,
1:1 dilution
Ankle
1ml Flow Graft,
1:1 dilution
Subtalar &
Midfoot Joints
0.5ml Flow Graft,
1:1 dilution
MPJ’s & Toes
(per joint)
0.25ml Flow Graft,
1:1 dilution
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No anti-inflammatories or ASA (6 weeks pre & post)
Increased tissue vascularity improves cellular
incorporation
Lidocaine 1% preservative free as carrier
Full activity (restrictions only if warranted by diagnosis)
No issues with icing or polar care machine
Not use – systemically, open growth plates, oncologic
process, active infection
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Nanofactor Flow is an alternative therapy to treat
inflammatory and degenerative musculoskeletal
conditions.
It makes sense given what we know about orthobiologic
principles with MSCs, growth factors and scaffolds
Patients are asking for this type of treatment
The cost is not prohibitive
Early observations very encouragin
We need more prospective data at all levels
◦ Dosing
◦ Efficacy
◦ Indications/Contraindications