-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
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•
•
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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Enabling Innovation
Dr. Bill Futrell, et al – Univ of Pittsburgh 1998
“Discovered true stem cells in fat that could create new tissues like bone and cartilage”
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
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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
Inflammation
Acute Injury
“Regeneration” Fibrosis
QUICK
FIX
Time
Scar Complete
Courtesy, A Caplan, Case
Western Reserve
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Stem Cells in Injury Response
“Regeneration”
Inflammation
Acute Injury
Time
Stem Cells
Fibrosis
Scar Reduced
Courtesy, A Caplan, Case
Western Reserve
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Roles / Functions
“Stem cells are injury-specific, perfectly choreographed pharmaceutical factories”
Dr. Arnold Caplan
Case Western Reserve
Influence by injury micro-environment
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Stem Cells and Joint Therapy Mechanisms
Chondrogenesis 1 - new cartilage formation
Lubricin 2 - lubricate joint, improve range of motion
IRAP Secretion 3 - blocks IL-1 inflammation mediator
Decrease Inflammation 4 - reduce pain and swelling
1 Wei et al, Cytotherapy , 2007
2 Lee et al, BBRC , 2008
3 Ortiz et al , PNAS 2007
4 Tholpady , Plast Surg , 2006
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Evidence-based Cell Therapy
DATA TYPE AVAILABLE
In-vitro (lab bench)
Lab Animal
Case Studies
Retrospective Studies
Non-Random, Prospective
Randomized, Controlled
Human Clinical Studies
STATUS
Canine
Osteoarthritis
X
X
X
X
X
X
X
Supported
Canine Tendon and Ligament
X
X
X
X
X
(equine)
X
Supported
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Rabbit Osteochondral Defect
Repair 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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Bilateral Stifle / Hips
4 YO Rat Terrier
Post Treatment:
2 weeks – Dramatic pain reduction
Now NSAID free for
>24 months
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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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3.5
Elbow OA Pilot Study (n=12)
3.0
2.5
2.0
1.5
1.0
0 30 60 90 180
Days Since Intraarticular Stem Cell Injection
(1=normal)
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Lame walk
Lame trot
Pain
Range Motion
Disable

• 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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Chronic Knee – Post-surgical OA
Pilot Study (n=9)
• 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
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4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Chronic Knee - Post-surgical OA
Pilot Study (n=9)
V-Lame
V-ROM
V-Pain
O-Lame
O-Stiffness
O-Pain
O-Energy
0 30 90 180
Days Post Stem Cell Treatment
1=normal, 2=mild, 3=mod, 4=severe
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Tendon / Ligament Clinical Data
Equine – Blinded, placebo-controlled study 1
Equine – Retrospective 2 – tendonitis
Equine – Retrospective 3 - ligament therapy
Canine – Clinical case studies 4
Canine – Retrospective analysis 5
Canine – Prospective, non-randomized 6 – shoulder instability
1 Nixon et al, AJVR , 2007
2 Meredith et al, ACVIM, 2006
3 Harman , VOS, 2007
4 Bausman, IFATS, 2008
5 Harman et al, IFATS, 2007
6 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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Safety Profile*
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
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Quality Standards
• 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
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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-up
 Risk Assessment of Concurrent Diseases
 Proper Collection – close dead space
 Proper use of Kit
 Proper Injection Technique
 Follow up and Rehab Program
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Case Selection for OA
• Ideal Stem Cell Case
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• Clearly defined disease – lameness
Non-surgical candidate – surgery first, if needed
• Limited intra-articular osteophytes
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•
•
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• One or two joints
No other major systemic diseases
No major spinal disease
NSAID – non-responsive or lack of tolerance
Owner has rational expectations
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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 Indications
Canine/Feline
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•
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• 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*
3.5
3.0
2.5
2.0
1.5
1.0
Day 0 30 60 90 Day 0 30 60 90 Day 0 30 60 90
Pain
(N=141, pre-tx)
Lameness
(N=146, pre-tx)
Range Of Motion
(N=141, pre-tx)
Veterinary
Scale:
5=Extreme
(considering euthanasia)
4=Severe
3=Moderate
2=Mild
1=Normal
*Voluntary responses from commercial cases.
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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= 139 owner voluntary responses 10/08- 05/09
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• 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
Cardiac
Muscle
Liver
Nerve
Fat-derived
Stem Cells
Angiogensis/
Anti-apoptosis
Bone
Fat
Cartilage Gene Therapy
Tholpady et al, Clin Plastic Surg, 2006
(Photo courtesy Cytori Therapeutics)
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Mechanisms of Repair
4. Homing to injury site
Damaged cartilage
MSCs
Photo Courtesy Cognate Therapeutics
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Mechanisms of Repair
5. Immune System Modulation
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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Vet-Stem Adipose Collection Kit
1. Sterile Collection tubes
2. Cryo-block
3. Submission form
4. Owner Consent form
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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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