14th Annual IFATS Meeting November 17-20, 2016 San Diego, California: AUTOLOGOUS MICRO-FRAGMENTED ADIPOSE TISSUE IN DOGS WITH ARTHROPATIES: SAFETY, FEASIBILITY AND CLINICAL OUTCOME. By Offer Zeira, San Michele Veterinary Hospital

1. 14th Annual Meeting
November 17-20, 2016
San Diego, California
AUTOLOGOUS
MICRO-FRAGMENTED ADIPOSE TISSUE IN
DOGS WITH ARTHROPATIES:
SAFETY, FEASIBILITY AND CLINICAL OUTCOME
Offer Zeira
San Michele Veterinary Hospital

2. Regenerative Medicine
In nature there
are plenty of
examples

3. Regenerative Medicine
And in these
orthopedic
cases?

4. Regenerative Medicine
Depends what do we aim for…
1) Recreation of new organs? NO
2) Regeneration of some tissues? MAYBE
3) Reduce inflammation and pain? YES
Prometheus will have to wait…
improve the quality of life

5. Regenerative Medicine
Colture of various
stem cells from
different origin

6. Regenerative Medicine –
modification of our approach
• Stem cells from bone marrow or adipose tissue needs
colture (12-15 days). OK for IV & heterologous use
• For arthropaties we looked for a product that has the
same capability but do not need colture. OK only for
autologous and local administration!!!

7. Device and procedure
Ideally we looked for:
• A disposable device for liposuction and
processing of adipose tissue
• The entire procedure is done in one session
• Reduction of adipose tissue clusters size,
eliminating pro-inflammatory oily and blood
residuals
• Closed aseptic system, minimal manipulation,
enzyme-free

8. • To verify clinical safety and efficacy of the device for
advanced therapy
• Quality and quantitative evaluation of the device’s
outcomes
Patient Selection
• 109 dogs (236 affected joints)
• From 8 months to 14 years old
• Single or multiple arthropaties, otherwise
healthy
Aim
Canine arthropaties - safety and efficacy of
microfragmented adipose tissue treatment

9. Canine arthropaties - safety and efficacy of microfragmented
adipose tissue treatment
Diseases treated:
• Vascular (Legg-Calve-Perthes disease)
• Immune mediated arthritis (OA)
• Traumatic injury (crCr ligament and meniscus
rapture, joint fractures)
• Hereditary/developmental (UAP, FCP, OCD, IOHC –
incomp. ossif. Of humeral condyle)
• DJD
Joints treated:
• Hip, stifle, elbow, shoulder, carpus and tarsus.

10. Canine Osteoarthrosis: safety and efficacy of
microfragmented adipose tissue treatment
Orthopedic examination
• Complete check up (CBC + biochemistry)
• RX (3/4 projections)
In case of severe DJD/OA:
• MRI
• Synovial fluid analisys
• IA treatment
Outcomes assesment:
• Control at 1, 3 and 6 months: clinical examination, RX and MRI
• Maximum of 24 months of fully documented follow-up
• Post mortem joint histology
Project Design

11. Device and procedure
Lipogems device was chosen
for adipose tissue harvesting

12. Device and procedure

13. Device and procedure

14. Device and procedure

15. Device e procedura
IA administration and cryoconservation

16. 1) imaging diagnostics
assessment (blind exam)
Results

17. 2) Cytologic & histologic assessment
Results

18. Results
3) Clinical assessment
Gilda, GSD, F, 8Y, UAP, DJD
10.5.15
3 days pre-
treatment
18.5.15
5 days post-
treatment
23.5.15
10 days post-
treatment

19. ORTHOPEDIC CASES
Gilda, GSD, F, 8Y, UAP

20. ORTHOPEDIC CASES
Gilda, GSD, F, 8Y, UAP
12.1.16
8 months post-
treatment
4.5.16
1 year post-
treatment

21. English Setter, M, 2Y,
Old elbow fracture
16.6.15, 16 days post-treatment
4.6.15, pre-treatment

22. Orthopedic assessment
• Lameness – 41% normalized, 54% improved, 5% not improved or worsen
• Improvement initiated 3 to 23 days after the treatment and continued gradually
up to 4 months
Imagining diag. assessment
• In some cases x-rays and MRI presented reduced bone spurs
Cytologic assessment
• In 92% of the treated articulations synovial fluid analysis showed improvement
Results
Safety & feasibility
• hematology and imaging diagnostics results after administration showed no
worsening of previous clinical status and no onset of new pathologies
• intra-articular injection showed no difficulty and no irreversible adverse
reaction (2 cases of septic arthritis – 1.8%)
Safety, feasibility and clinical results of treatment in
109 dogs with arthropaties

23. Results
Histologic assessment
• Microscopic changes characteristic of osteoarthrosis
• Minimal inflammatory changes in bone marrow and joint synovial membrane
• Remnants of the injected material in clusters (large eosinophilic cells with
vacuoles, empty adipocytes, stromal cells, high numbers of MSCs and pericytes,
abundant microvascular endothelial cell)
Safety, Feasibility and clinical results of treatment in
109 dogs with arthropaties
AdipocytesStromal cells Reticular stroma

24. Conclusions
1. Adipose tissue contain, adipocytes and heterogeneous population of
hematopoietic cells, pericytes, endothelial cells and progenitors, and
stromal/stem cells. IA treatment with these elements is safe and feasible
in dogs with OA.
2. Our clinical results supports in vitro reports describing Lipogems as an
effective preparation of fat-derived tissue that retains either per se, or in
its embedded MSCs content, the capacity to induce vascular stabilization
and inhibit several macrophage functions involved in inflammation.
3. Further histological investigation of treated joints is needed in order to
better understand the underlying mechanisms, however, the long term
survival of Lipogems clusters within the treated joints, may explain the
long term efficacy of the treatment
4. Lipogems preparation from dog’s adipose tissue can be easily expanded in
culture and its properties are not altered by cryoconservation
Safety and Feasibility of autologous MSCs
implantation in 109 dogs with arthropaties

25. THANK YOU
the perfect patient

26. Many thanks to:
STEM CELL LAB
Dr. Aralla Marina, DVM, Phd
Dr. Letizia Pettinari , MSC, Phd
Dr. Erica Ghezzi, BSC
RADIOLOGY
Dr. Martin Konar, DVM, Phd, dipl ECVN
Dr. Laura Martinelli, DVM, MA imag.diag.
Dr. Davide Moscarello , RT
SURGERY
Dr. Daniele Zahirpour, DVM
Dr Nimrod Asiag, DMV
Dr. Simone Scaccia, DMV
Dr. Maria Pia Dumas, DMV
ANIMALS CARE AND REHAB
Dr. Michela Lionello, VT
Dr. Lorenza Sironi, DVM
FACS ANALISYS
Dr. Stefano Comazzi, DVM, PhD, dipl ECVCP
CYSTOLOGIC ANALISYS
Dr. Davide Lupi DMV
HYSTOLOGIC ANALISYS
Dr. Luisa Pascucci, DVM, PhD
Dr. Laurence Fiette, DVM, PhD