Download Regenerative Medicine Credentialing Course - Vet-Stem

-Stem Cell Therapy Introduction and Practical Guide to
Use in Small Animal Practice
6650-0018-002
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.
6650-0018-002
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
6650-0018-002
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.
6650-0018-002
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
in the lab
Fix fractures
6650-0018-002
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
6650-0018-002
What Cells Do We Use?1
6650-0018-002
Mechanisms of Repair
• Trophic support - growth factors and cytokines
• Anti-inflammatory
• Differentiation into tissue
• Homing to injury site
• Immune System Modulation
6650-0018-002
The Injury Response Cascade
Magnitude
Inflammation
“Regeneration”
Fibrosis
QUICK
FIX
Acute Injury
Time
Scar Complete
Courtesy, A Caplan, Case
Western Reserve
6650-0018-002
Magnitude
Stem Cells in Injury Response
“Regeneration”
Inflammation
Fibrosis
Time
Acute Injury
Stem Cells
Scar Reduced
Courtesy, A Caplan, Case
Western Reserve
Roles / Functions
“Stem cells are injury-specific, perfectly
choreographed pharmaceutical factories”
Dr. Arnold Caplan
Case Western Reserve
Influence by injury micro-environment
6650-0018-002
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
2
3
4
Wei et al, Cytotherapy, 2007
Lee et al, BBRC, 2008
Ortiz et al, PNAS 2007
Tholpady, Plast Surg, 2006
6650-0018-002
Evidence-based Cell Therapy
DATA TYPE AVAILABLE
Canine
Osteoarthritis
Canine 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
6650-0018-002
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.
6650-0018-002
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!
6650-0018-002
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
6650-0018-002
Bilateral Stifle / Hips
4 YO Rat Terrier
Post Treatment:
2 weeks – Dramatic
pain reduction
Now NSAID free for
>24 months
6650-0018-002
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
6650-0018-002
• 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
6650-0018-002
Elbow OA Pilot Study (n=12)
3.5
Parameter Score (1-5)
3.0
2.5
Lame walk
Lame trot
2.0
Pain
Range Motion
1.5
Disable
1.0
0
30
60
90
180
Days Since Intraarticular Stem Cell Injection
(1=normal)
6650-0018-002
• 180 Day Study – Blinded/Placebo
• Bilateral Hip OA – 18 dogs
• Intra-articular stem cells – 1X
• Vet/Owner assessments at pre, 30, 60, 90
6650-0018-002
6650-0018-002
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
6650-0018-002
Chronic Knee - Post-surgical OA
Pilot Study (n=9)
4.0
Parameter Score (1-5)
3.5
3.0
V-Lame
2.5
V-ROM
2.0
V-Pain
1.5
O-Lame
1.0
O-Stiffness
O-Pain
0.5
O-Energy
0.0
0
30
90
180
Days Post Stem Cell Treatment
1=normal, 2=mild, 3=mod, 4=severe
6650-0018-002
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
2
3
4
5
6
Nixon et al, AJVR, 2007
Meredith et al, ACVIM, 2006
Harman, VOS, 2007
Bausman, IFATS, 2008
Harman et al, IFATS, 2007
Canapp, AVMA, 2009
6650-0018-002
•
8 Horses – 4 treated / 4 controls
•
Collagenase induced injury – Rx 10 days later
•
Fully blinded histology
•
Controls were treated with same volume of
saline
6650-0018-002
Stem
Cell
Treated
Saline
Control
Outcome:
Less scar - More normal tendon
Statistically improved tendon healing
6650-0018-002
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
6650-0018-002
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
6650-0018-002
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
6650-0018-002
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
6650-0018-002
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
6650-0018-002
Case Selection for OA
•
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
6650-0018-002
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
34
6650-0018-002
Current Supported Indications
Canine/Feline
•
•
•
•
Osteoarthritis
Polyarthritis
Tendonitis
Ligament injury
6650-0018-002
Service Overview
6650-0018-002
Vet-Stem Adipose Processing Lab
1. Immediate use
3. Lifetime supply
by culture
2. Frozen for future
6650-0018-002
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
Veterinary
Scale:
5=Extreme
(considering
euthanasia)
4=Severe
3=Moderate
2=Mild
1=Normal
Veterinary Score
3.0
2.5
2.0
*Voluntary
responses from
commercial
cases.
1.5
1.0
Day 0
30
60
90
Pain
(N=141, pre-tx)
Day 0
30
60
90
Lameness
(N=146, pre-tx)
Day 0
30
60
90
Range Of Motion
(N=141, pre-tx)
6650-0018-002
Change in NSAID Usage in Dogs
Treated with Stem Cells for Osteoarthritis
90 Days Post Stem Cell Treatment
survey range: 76 -105 days, N= 170
owner voluntary responses 10/08- 05/09
246 Days Post Stem Cell Treatment
survey range: 106 - 470 days, N= 139
owner voluntary responses 10/08- 05/09
6650-0018-002
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
6650-0018-002
6650-0018-002
Media Coverage of
Veterinary Medicine
6650-0018-002
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.
6650-0018-002
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
6650-0018-002
Mechanisms of Repair
2. Anti-inflammatory
• Decrease pro-inflammatory mediators
• Increase anti-inflammatory mediators
Tholpady et al, Clin Plastic Surg, 2006
6650-0018-002
Mechanisms of Repair
3. Differentiation into tissue
Muscle
Liver
Cardiac
Nerve
Fat-derived
Stem Cells
Angiogensis/
Anti-apoptosis
Bone
Fat
Cartilage
Gene Therapy
Tholpady et al, Clin Plastic Surg, 2006
(Photo courtesy Cytori Therapeutics)
6650-0018-002
Mechanisms of Repair
4. Homing to injury site
Damaged cartilage
MSCs
Photo Courtesy Cognate Therapeutics
6650-0018-002
Mechanisms of Repair
5. Immune System Modulation
Stem cells down-regulate the immune system attack on
its own nerve sheath myelin.
6650-0018-002
Composite Score: Lameness at walk
Lameness at trot
Pain on manipulation
Range of motion
Functional disability
6650-0018-002
Vet-Stem Adipose Collection Kit
1. Sterile Collection tubes
2. Cryo-block
3. Submission form
4. Owner Consent form
6650-0018-002
Adipose Tissue Harvest
Falciform Fat
Most preferred
collection location due to
low risk of seroma and
adequate fat source
6650-0018-002
Adipose Tissue Harvest
Thoracic Approach
6650-0018-002