-stem cell therapy - introduction and practical guide to use in small animal practice 6650-0018-002
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-Stem Cell Therapy -Introduction and Practical Guide to
Use in Small Animal Practice
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What Do Stem Cells Do?
10 million cells die in your body every minute of every day.
Your own stem cells replace them so you can continue living.
This is what stem cells do for a living.
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What are Stem Cells?
Stem Cells are Primitive cells present in almost every tissue:
• Self Renewing• Able to become different tissue types• Trophic Factories – Growth Factors
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Embryonic vs Adult Stem Cells
Stem Cells from Embryos
• Intended to form whole animal - not for repair• Can form tumors – UNPREDICTABLE• Maybe someday
Adult Stem Cells – many sources
• Intended for self repair• Do not form tumors when injected• Now
Gruen L and Grabel L, Stem Cell 2006;24;2162-2169.
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Dr. Bill Futrell, et al – Univ of Pittsburgh 1998“Discovered true stem cells in fat that couldcreate new tissues like bone and cartilage”
Enabling Innovation
Stem Cells from fat Extracted can become bone Fix fractures in the lab
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Why Adipose as Stem Cell Source?
High healing cell count – No culturing required
1000X stem cell concentration as bone marrow
Family of healing cells - heterogeneous
Rapid, Easy to access
Over 1700 peer reviewed papers published
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What Cells Do We Use?1
1 Varma et al, Stem Cells and Development 2007:91-104 (freshly isolated adipose).Repeated by Collas et al and Yoshimura et al.
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Mechanisms of Repair
• Trophic support - growth factors and cytokines
• Anti-inflammatory
• Differentiation into tissue
• Homing to injury site
• Immune System Modulation
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The Injury Response Cascade
Time
Fibrosis
Inflammation
“Regeneration”
Acute InjuryAcute Injury Scar Complete
Ma
gn
itu
de
QUICK QUICK FIXFIX
Courtesy, A Caplan, Case Western Reserve
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“Regeneration”
Acute InjuryAcute Injury Scar Reduced
Time
Ma
gn
itu
de
Inflammation
Fibrosis
Stem Cells in Injury Response
Courtesy, A Caplan, Case Western Reserve
Stem CellsStem Cells
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Roles / Functions
“Stem cells are injury-specific, perfectly choreographed pharmaceutical factories”
Dr. Arnold CaplanCase Western
Reserve
Influence by injury micro-environment
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Stem Cells and Joint Therapy Mechanisms
Chondrogenesis1 - new cartilage formation
Lubricin2 - lubricate joint, improve range of motion
IRAP Secretion3 - blocks IL-1 inflammation mediator
Decrease Inflammation4 - reduce pain and swelling
1 Wei et al, Cytotherapy, 20072 Lee et al, BBRC, 20083 Ortiz et al, PNAS 20074 Tholpady, Plast Surg, 2006
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Evidence-based Cell Therapy
DATA TYPE AVAILABLECanine
OsteoarthritisCanine Tendon and Ligament
In-vitro (lab bench) X X
Lab Animal X X
Case Studies X X
Retrospective Studies X X
Non-Random, Prospective X X
Randomized, Controlled X (equine)
Human Clinical Studies X X
STATUS Supported Supported
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Rabbit Osteochondral DefectRepair Model
Nathan et al, “Cell-based therapy in the repair of osteochondral defects: A novel use for adipose tissue” Tissue Engineering, 2003.
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Elbow Dysplasia - DJD
Annie – 9 YO
Chronic elbow dysplasia – non-NSAID controlled pain
Stem Cell Therapy at Day 0 and 14.
Now able to jump in and out of car; took 2 hour run in the woods before her 90 day study exam!
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Bilateral Stifle / Hips
4 YO Rat Terrier
Bilateral stifle and hip degeneration since 6 months old
NSAIDS for 12 months and still painful
===============
Intra-articular RX with Stem cells in all four joints
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4 YO Rat Terrier
Post Treatment:
2 weeks – Dramatic pain reduction
Now NSAID free for >24 months
Bilateral Stifle / Hips
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Human Therapy
“Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report”
A young girl with major trauma to skull cap that could not be repaired with bone graft was treated with her own adipose stem cells and re-grew the skull bones.
Journal of Cranio-Maxillofacial Surgery (2004) 32, 370–373
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• 180 Day Prospective, Non-randomized Study
• Uni or Bilateral Elbow OA
• Intra-articular stem cells 1x
• Vet and Owner assessments at pre, 30, 60, 90, 180
• 14 dog study
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1.0
1.5
2.0
2.5
3.0
3.5
0 30 60 90 180
Para
met
er S
core
(1-5
)
Days Since Intraarticular Stem Cell Injection(1=normal)
Elbow OA Pilot Study (n=12)
Lame walk
Lame trot
Pain
Range Motion
Disable
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• 180 Day Study – Blinded/Placebo
• Bilateral Hip OA – 18 dogs
• Intra-articular stem cells – 1X
• Vet/Owner assessments at pre, 30, 60, 90
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• 180 Day Pilot Study, 9 dogs
• Chronic Post-Surgical OA (>3 Mo)
• Intraarticular stem cells – 1X
• Vet and Owner assessments at pre, 30, 90, 180
• Not Blinded
Chronic Knee – Post-surgical OA Pilot Study (n=9)
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0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
0 30 90 180
Para
met
er S
core
(1-
5)
Days Post Stem Cell Treatment1=normal, 2=mild, 3=mod, 4=severe
Chronic Knee - Post-surgical OA Pilot Study (n=9)
V-Lame
V-ROM
V-Pain
O-Lame
O-Stiffness
O-Pain
O-Energy
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Tendon / Ligament Clinical Data
Equine – Blinded, placebo-controlled study1
Equine – Retrospective2 – tendonitis
Equine – Retrospective3 - ligament therapy
Canine – Clinical case studies4
Canine – Retrospective analysis5
Canine – Prospective, non-randomized6 – shoulder instability
1 Nixon et al, AJVR, 20072 Meredith et al, ACVIM, 20063 Harman, VOS, 20074 Bausman, IFATS, 20085 Harman et al, IFATS, 20076 Canapp, AVMA, 2009
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• 8 Horses – 4 treated / 4 controls
• Collagenase induced injury – Rx 10 days later
• Fully blinded histology
• Controls were treated with same volume of saline
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Stem Cell
Treated
Saline Control
Outcome: Less scar - More normal tendon Statistically improved tendon healing
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Why Use Vet-Stem?
• Began treating horses in 2003
• Global patents/licenses (over 55 issued patents)
• Over 3,000 horses and 2,000 dogs treated
• Global leader in stem cell therapy
• Peer-reviewed, published controlled studies
• High quality laboratory
• Human stem cell alliances
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Horses:7/3,359 (0.2%) Only local swelling/pain No systemic effects
Dog: 2/1,695 (0.1%) Only local swelling/pain
No systemic effects
*probable adverse events, through 6/1/09
Safety Profile*
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• Written standard operating procedures
• Independent Quality Assurance Unit
• Routine audits of all procedures
• Sample release criteria
• Formal training systems
• Environmental monitoring
• All Handling Done In Sterile Hoods
Quality Standards
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Resources from Vet-Stem
• Technical training – course & consultation• Case selection - consultation• Cell banking• Lifetime cell supply – Cell Culture Service• Marketing Kit
• Owner email support• Clinic DVD – waiting room• Brochures, posters, counter-top displays• Power Point presentations• Co-op Advertising• Newsletters
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Keys to Success
Credentialing Course (www.vet-stem.com)Complete Diagnostic Work-upRisk Assessment of Concurrent DiseasesProper Collection – close dead spaceProper use of KitProper Injection TechniqueFollow up and Rehab Program
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• Ideal Stem Cell Case• Clearly defined disease – lameness• Non-surgical candidate – surgery first, if needed• Limited intra-articular osteophytes• One or two joints• No other major systemic diseases• No major spinal disease• NSAID – non-responsive or lack of tolerance• Owner has rational expectations
Case Selection for OA
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Cruciate Ligament Diseases and the Uses of Stem Cells
• Surgery – always assess need and make appropriate surgical repairs
• At surgery – adjunct to reduce inflammation and scar tissue
• After surgery – treat the synovitis and encourage cartilage repair
• Chronic ACL inflammation and synovitis
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Current Supported IndicationsCanine/Feline
• Osteoarthritis• Polyarthritis• Tendonitis• Ligament injury
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Service Overview
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Vet-Stem Adipose Processing Lab
1. Immediate use
3. Lifetime supply by culture
2. Frozen for future
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Real World Dog OA Cases
Average Veterinary Scores of Dogs in Regards to Pain, Lameness, and Range of Motion
2008 Commercial Clinical Data*
1.0
1.5
2.0
2.5
3.0
3.5
Pain(N=141, pre-tx)
Lameness(N=146, pre-tx)
Range Of Motion(N=141, pre-tx)
Ve
teri
na
ry S
co
re
Veterinary Scale:5=Extreme (considering euthanasia)4=Severe3=Moderate2=Mild1=Normal
*Voluntary responses from commercial cases.
Day 0 30 60 90 Day 0 30 60 90 Day 0 30 60 90
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Change in NSAID Usage in Dogs Treated with Stem Cells for Osteoarthritis
90 Days Post Stem Cell Treatment 246 Days Post Stem Cell Treatment
survey range: 76 -105 days, N= 170 owner voluntary responses 10/08- 05/09
survey range: 106 - 470 days, N= 139owner voluntary responses 10/08- 05/09
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Conclusion: At 90 and 246 days after treatment
• Greater than 33% of dogs discontinued the use of NSAIDs completely
• Greater than 28% of dogs decreased their dependency on NSAIDs
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Media Coverage of Veterinary Medicine
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Additional Slides
The additional slides that follow are intended to be supplementary information and can be used to emphasize a particular area of the talk or to modify the theme or direction of the talk for the intended audience.
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Mechanisms of Repair
1. Trophic support – growth factors and cytokines
• Anti-scarring - MMPs (reduce scar tissue formation)
• Angiogenic - VEGF (induces new blood vessels)
• Anti-apoptotic (block cell death after injury)
• Stimulation of resident tissue stem cells
Caplan and Dennis, J Cell Biochem, 2006
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Mechanisms of Repair
2. Anti-inflammatory
• Decrease pro-inflammatory mediators
• Increase anti-inflammatory mediators
Tholpady et al, Clin Plastic Surg, 2006
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Mechanisms of Repair
3. Differentiation into tissue
Tholpady et al, Clin Plastic Surg, 2006
(Photo courtesy Cytori Therapeutics)
NerveNerve
BoneBone
CartilageCartilage
LiverLiver
Fat-derivedFat-derivedStem CellsStem Cells
CardiacCardiac
FatFat
Angiogensis/Angiogensis/Anti-apoptosisAnti-apoptosis
Gene TherapyGene Therapy
MuscleMuscle
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Mechanisms of Repair
Damaged cartilage
MSCs
4. Homing to injury site
Photo Courtesy Cognate Therapeutics
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5. Immune System Modulation
Mechanisms of Repair
Stem cells down-regulate the immune system attack on its own nerve sheath myelin.
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Composite Score: Lameness at walk Lameness at trot Pain on manipulation Range of motion Functional disability
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1. Sterile Collection tubes
2. Cryo-block
3. Submission form
4. Owner Consent form
Vet-Stem Adipose Collection Kit
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Adipose Tissue Harvest Falciform Fat
Most preferred collection location due to low risk of seroma and adequate fat source
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Adipose Tissue Harvest Thoracic Approach
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