an alternative in managing knee arthritis phil davidson, md park city, ut
TRANSCRIPT
NANOFACTOR FLOW Stem Cell Therapy
An Alternative in Managing Knee Arthritis
Phil Davidson, MDPark City, UT
NSAIDS PT Weight loss Bracing Injection Therapy
◦ Corticosteroids◦ Viscosupplementation◦ PRP◦ Autologous MSC’s (BMA derived)◦ Amniotic Tissue Graft-Allogeneic MSC
Non-Operative Management of Knee OA
Corticosteroids-good and bad…. Viscosupplementation: unpredictable, often ineffective, only potential to address aching, no reparative capacity, many insurances are not authorizing
Legacy Injection Therapies
CORTICOSTEROID BENEFITS Rapidly reduce pain due to inflammation Last for several weeks to months Joints, Spine radiculopathy, Bursitis, Tendonitis, Neural
inflammation (CTS)
CORTICOSTEROID SIDE EFFECTSSHORT TERM USE Atrophy Depigmentation Hyperglycemia Infection Post injection flare Tissue structure weakening, tendon ruptures
Chondrocytes and MSCs exposed to PRP show increased cell proliferation and cartilage extra-cellular matrix synthesis of PG and Type II collagen
Synoviocytes cultured in PRP produce more HA-better 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?
PRP in Cartilage Repair
Biologic treatment is interactive KEY ELEMENTS ALL REQUIRED:
◦Growth factors, cells, scaffold◦Mechanically favorable environment
A “Nutrient Rich Soup” includes-◦Cells (RBC, white cells, MSC)◦Growth factors (from platelets or plasma)◦Scaffolds
Potential sources of this “Soup”: ◦Bone Marrow Aspirate, Amniotic Fluid
BIOLOGICSKnee OA
MSC’s are undifferentiated cells:◦ Capacity for prolonged self-renewal◦ Ability to differentiate into specialized cell types
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
MSC’s in Sports Medicine
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
Mesenchymal Stem Cells in Sports Medicine
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
Mesenchymal Stem Cells in Sports Medicine
Increased meniscal volume in post-menisectomy 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
Mesenchymal Stem Cells Reparative Promise in Knee OA
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
Mesenchymal Stem Cells Reparative Promise in Knee OA
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
Amniotic Membrane and Fluid Allograft
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 ischemiaStem cells and development vol23, 20, 2014
(3)Karantalis, MSc w CABG circulation research Feb 2014
NANOFACTOR™ FLOW 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
PRP1 Element TxBMA2 Element TxNanofactorAll Elements
Amniotic Membrane
Scanning Electron Microscopic image of cryofractured amniotic membrane particles.
Membrane particle
Amniotic ScaffoldingCryofractured Amnion
Nanofactor Minimally Manipulated Extracellular Matrix
Morcelized TissueDisrupted 3D Structure
CryoFractured TissueIntact 3D Structure
Growth factors Scaffolding Cells and lots of them and immature-pluri-
potential-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
What makes Nanofactor Flow different?
Amnio vs BMA: MSC Volume Comparison
Amniotic 440,000 MSC’s/1ml
Bone Marrow Aspirate1,600 MSC’s/1ml
Jing Li et al: Chin J Cancer Res 23(1): 43-48, 2011
Human MSCs Decline with Age
Adopted from: Al Caplan. J Pathol 2009; 217:318-314, 2008
Age (Years)
MS
Cs
pe
r M
arr
ow
Ce
lls
Newborn Teen 30 50 80
_______1,000
1
_______100,000
1_______250,000
1_______400,000
1_______
2,000,000
1
Estimates obtained by
CFU- f assay
Relative Number of MSC’s by Age
Adopted from: Al Caplan. J Pathol 2009; 217:318-314, 2008
Age (Years)
MS
Cs
pe
r M
arr
ow
Ce
lls
Newborn Teen 30 50 80
2000 400 250 100 1
Amniotic Tissue AllograftNanofactor FLOW
Growth Factors/Peptides
Cellular Components
Extracellular Matrix+ +
Shipping to Manufacturing Facility
Overnight at 1-10o C
Amniotic Placental Tissue Collection Scheduled c-section
- Amniotic fluid (~ 650cc)- Amnion membrane (900 cm2)
ConsentInfectious Disease Testing
Tissue Processing
Processed in Class ISO 5 Bioburden Testing USP <61>Environmental MonitoringMicronized Amnion Growth Factors, Cytokines, ECM ProteinsViable Cells5% DMSO
Final Product Lot Release
Sterility Testing USP <71>Mycoplasma Testing USP <63>Endotoxin Testing USP < 85>
3-4 weeks
Product Packaging and Distribution
>65o C
“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
How do the sources compare?
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
Why do I offer my patients Nanofactor Flow?
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
How do I discuss Nanofactor Flow?
PHASE IGetting Started in the Office
+Dilutants & Nanofactor
CryoFreezer: If you plan to do
any volume
• (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
Acceptable Dilutants
Flow
• 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.
Unacceptable DilutantsFlow
Preparation & Mixing1. Remove the package from freezer or dry
ice container. Cut the package. *Outside of vial is not sterile
2. Defrost vial by holding still in hand for 3-5 minutes. *Do not shake vial
3. Fill syringe with dilutant. (typically 1:1 ratio)
4. Draw Nanofactor™ Flow into syringe with 18g needle.
5. Use a 22 or 23g needle for injection but nothing smaller than a 23g
Flow
Shoulder 1ml Flow Graft,1:2 up to 1:4 dilution Elbow 1ml Flow Graft,1:1 dilution Wrist, Fingers & Facets(per joint)0.25ml 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
Hip2ml Flow Graft,1:2 up to 1:3 dilution Knee(per compartment)Stage 3: 0.5ml Flow Graft,Stage 4: 1ml Flow Graft,1:2 dilution Ankle1ml Flow Graft,1:1 dilution
Recommended Joint DosingFlow
PEARLS 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
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
Summary
Thank You [email protected]