1. THE USE OF STEM CELLS AS A REGENERATIVE THERAPY FOR CHRONIC LAMINITIS Nikki Engwall Penn State University

2. Overview- Laminitis  Caused by:  Endocrinatic diseases  Systemic infections  Non-weight bearing lameness  Symptoms include lameness, heat in affected foot, reluctance to walk, change in stance, change in hoof shape

3. Distal Phalanx Displacement  Inflammation damages laminar attachments, causing distal phalanx to displace  Scar tissue sometimes forms between displaced coffin bone and hoof wall, called the laminar wedge, measured by hoof laminar zone (HLZ)  Types of displacement  Rotation  Sinking

4. Distal Phalanx Laminar Wedge Hoof Wall Deep Digital Flexor Tendon Pull from DDFT

5. Deep Digital Flexor Tendon Compressed Digital Cushion Distal Phalanx Laminar Wedge WeightWeight HLZ

6. Common Treatments  NSAIDS and analgesics  Corrective padding and shoeing  Dorsal wall resection  Deep digital flexor tenotomy  Regardless of treatment, success rates are low with chronic laminitis cases

7. Regenerative Therapy  Use of pluripotent mesenchymal stem cells (MSC) to repair musculoskeletal tissue  Harvested from horse’s blood, bone marrow, or fat cells  Inhibit scar formation and cell death, increase blood flow, stimulate growth of new cells, release growth factors and anti-inflammatory proteins

8. Use in Treating Laminitis  Study at Rood and Riddle Equine Hospital in Kentucky tested MSC treatment in 30 horses, age 2-20 diagnosed with chronic laminitis  Six classified as severe rotation with moderate bone disease, six with rotation and severe bone disease, and 18 as sinking  Each received 20-30 million MSC in each affected foot in one month intervals  Average 3-4 treatments per horse

9. Results of Study  Treatment found to be successful if horse was pasture sound without maintenance or heavy medication for one year  21 of the 30 cases were successful (70%)  15 of the 18 sinkers were successful (83%) (Dryden, Vernon C et al. Using stem cells in clinical cases. Journal Equine Veterinary Sci. Oct 2013)

10. Results continued  The sooner the horse received treatment, the better  Median time to first treatment was 71.5 days  13 of the 15 horses treated before 71.5 days were successful (87%)  8 of the 15 treated later were successful (53%) (Dryden, Vernon C et al. Using stem cells in clinical cases. Journal Equine Veterinary Sci. Oct 2013)

11. Results continued Growth of laminar wedge has negative effect  Scar tissue generally forms around 90 days  11 of the 16 horses first treated before 90 days had improved HLZ (69%)  2 of the 12 horses treated after formation of the laminar wedge showed improved HLZ (17%)  Similar to earlier study published in 2011 In JEVS, 83% found successful using allogenic MSCs (Dryden, Vernon C et al. Using stem cells in clinical cases. Journal Equine Veterinary Sci. Oct 2013)

12. Future applications  Questions still remain  How should the stem cells be given for optimum results?  Where is the best place to give stem cells?  What is the best kind of stem cells to use?  Lack of information on long term effects  Safety concerns and possible interactions with other biological molecules.

13. In Conclusion…  Stem cell therapy has been known to be successful in treating various orthopedic injuries, but only recently has been studied in treating laminitis  Recent work has shown positive results in treating laminitis  Early intervention is key

14. References  Dryden, Vernon C et al. Using stem cells in clinical cases. Journal Equine Veterinary Sci. Oct 2013  Morrison, Scott. Successful use of allogenic umbilical cord-derived stem cells in nonresponsive chronic laminitic cases. Journal Equine Veterinary Sci. Oct 2011  Schnabel, Lauren V et al. Therapeutic use of stem cells in horses: Which type, how, and when?. The Veterinary Journal. Sept 2013

15. Thank You!  Are there any questions?