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IFATS Presentation by Dr offer Zeira - 2016 20.11.16

  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
  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