DOI
https://doi.org/10.18849/ve.v1i4.45Abstract
Objective: The primary objective of this study was to identify adverse events associated with multiple intra-articular injections of adipose stromal cell (ASC) therapy and secondarily to objectively assess the therapeutic effect of ASC therapy for treatment of fragmented medial coronoid process (FMCP) in dogs when used as an adjuvant to standard of care (SOC) treatment.
Background: Preliminary trials assessing autologous ASC therapy to treat osteoarthritis indicate a positive impact on clinical signs, but assessment of donated, allogeneic ASC therapy is lacking.
Evidentiary value: This prospective, randomised, controlled trial in dogs (n=30) provides objective evidence for clinical practitioners regarding ASC therapy in a naturally occurring osteoarthritic disease model.
Methods: Dogs diagnosed with FMCP and osteoarthritis were enrolled. All dogs had arthroscopic fragment removal and proximal ulnar osteotomy (PUO) and were assigned into three groups (n=10/group): 1) control group with no further treatment beyond the PUO and fragment removal (SOC), 2) PUO + autologous ASCs and 3) PUO+ allogeneic ASCs. Each dog had force platform gait analysis, Canine Brief Pain Inventory (CBPI) questionnaires, and delayed gadolinium enhanced magnetic resonance imaging scores prior to and six months after therapeutic intervention.
Results: No serious adverse events were reported in any participant. 3/10 dogs in the control group, 3/10 autologous ASC group and 7/10 allogeneic ASC group participants were assessed as successful outcomes.
Conclusion: This study provides preliminary safety data for the use of intra-articular allogeneic ASC therapy to treat osteoarthritis, and justification for larger clinical studies.
Application: Clinical practitioners considering ASC therapy within their practice are provided with additional evidence of autologous ASC therapy for osteoarthritis. Researchers committed to developing and generating effective ASC therapies are provided with safety information for allogeneic ASC, as well as identified biases important for study design.
References
Johnston, S.A. Osteoarthritis. Joint anatomy, physiology, and pathobiology. Vet Clin North Am Small Anim Pract. 1997;27(4):699-723. http://www.ncbi.nlm.nih.gov/pubmed/9243777. Accessed September 5, 2016.
Evans, R.B. Gordon-Evans, and WJ. Conzemius, M.G. (2008) Comparison of Three Methods for the Management of Fragmented Medial Coronoid Process in the Dog. Veterinary and Comparative Orthopaedics and Traumatology, 21 (2), pp. 106-109. http://dx.doi.org/10.3415/VCOT-07-04-0031
Ness, M.G. (1998) Treatment of fragmented coronoid process in young dogs by proximal ulnar osteotomy. Journal of Small Animal Practice, 39 (1), pp. 15-18. http://dx.doi.org/10.1111/j.1748-5827.1998.tb03663.x
Snelling, S.R. and Lavelle, R.B. (2004) Radiographic Changes in Elbow Dysplasia Following Ulnar Osteotomy--A Case Report and Review of the Literature. Australian Veterinary Journal, 82 (5), pp. 278-281. http://dx.doi.org/10.1111/j.1751-0813.2004.tb12703.x
Read, R.A. et al. (1990) Fragmentation of the Medial Coronoid Process of the Ulna in Dogs: A Study of 109 Cases. Journal of Small Animal Practice, 31 (7), pp. 330-334. http://dx.doi.org/10.1111/j.1748-5827.1990.tb00823.x
Black, L.L. et al. (2008) Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical Signs of Chronic Osteoarthritis of the Elbow Joint in Dogs. Veterinary Therapeutics. 9 (3), pp. 192-200.
Black, L.L. et al. (2007) Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Veterinary Therapeutics. 8 (4), pp. 272-284.
Guercio, A. et al. (2012) Production of canine mesenchymal stem cells from adipose tissue and their application in dogs with chronic osteoarthritis of the humeroradial joints. Cell Biology International, 36 (2), pp.189-194. http://dx.doi.org/10.1042/CBI20110304
Vilar, J.M. et al. (2013) Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Veterinary Research, 9 (1), p. 131. http://dx.doi.org/10.1186/1746-6148-9-131
Vilar, J.M. et al. (2014) Assessment of the Effect of Intraarticular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells in Osteoarthritic Dogs Using a Double Blinded Force Platform Analysis. BMC Veterinary Research, 10 (1), pp. 143 http://dx.doi.org/10.1186/1746-6148-10-143
Cuervo, B. et al. (2014) Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors. International Journal of Molecular Sciences, 15 (8), pp. 13437-13460 http://dx.doi.org/10.3390/ijms150813437
Vangsness, Jr, CTV. et al. (2014) Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy. The Journal of Bone and Joint Surgery-American Volume, 96 (2), pp. 90-98. http://dx.doi.org/10.2106/JBJS.M.00058
Lee, J.M. et al. Comparison of Immunomodulatory Effects of Placenta Mesenchymal Stem Cells with Bone Marrow and Adipose Mesenchymal Stem Cells. International Immunopharmacology, 13 (2), pp. 219-224 http://dx.doi.org/10.1016/j.intimp.2012.03.024
Melief, S.M. et al. (2013) Adipose Tissue-Derived Multipotent Stromal Cells Have a Higher Immunomodulatory Capacity Than Their Bone Marrow-Derived Counterparts. Stem Cells Translational Medicine, 2 (6), pp. 455-463 http://dx.doi.org/10.5966/sctm.2012-0184
Kang, J.W. et al. (2008) Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells. Stem Cells and Development, 17 (4), pp. 681-693 http://dx.doi.org/10.1089/scd.2007.0153
Caplan, A.I. (2007) Adult Mesenchymal Stem Cells for Tissue Engineering Versus Regenerative Medicine. Journal of Cellular Physiology, 213 (2), pp. 341-347. http://dx.doi.org/10.1002/jcp.21200
Kuo, Y.R. et al. (2011) Modulation of Immune Response and T-Cell Regulation by Donor Adipose-Derived Stem Cells in a Rodent Hind-Limb Allotransplant Model. Plast Reconstr Surg. 128 (6), pp. 661e - 672e. http://dx.doi.org/10.1097/PRS.0b013e318230c60b
Frisbie, D.D. et al. (2009) Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. Journal of Orthopaedic Research, 27 (12), pp.1675-1680 http://dx.doi.org/10.1002/jor.20933
Vilar, J.M. et al. (2013) Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Veterinary Research, 9 (11), pp. 131 http://dx.doi.org/10.1186/1746-6148-9-131
Caplan, A.I. and Dennis, J.E. (2006) Mesenchymal stem cells as trophic mediators. Journal of Cellular Biochemistry, 98 (5), pp.1076-1084 http://dx.doi.org/10.1002/jcb.20886
Wood, J.A. et al. (2012) Periocular and intra-articular injection of canine adipose-derived mesenchymal stem cells: an in vivo imaging and migration study. Journal of Ocular Pharmacology and Therapeutics, 28 (3), pp. 307-317.
Tyndall, A. and van Laar, J.M. (2010) Stem cells in the treatment of inflammatory arthritis. Best Practice & Research Clinical Rheumatology, 24 (4), pp. 565-574. http://dx.doi.org/10.1016/j.berh.2010.01.008
Cui, L. et al. (2007) Repair of cranial bone defects with adipose derived stem cells and coral scaffold in a canine model. Biomaterials, 28 (36), pp. 5477-5486 http://dx.doi.org/10.1016/j.biomaterials.2007.08.042
Arinzeh, T. and Peter, S. (2003) Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. The Journal of Bone and Joint Surgery-American Volume, 85 (10), pp.1927-1935. http://dx.doi.org/10.2106/00004623-200310000-00010
Jung, D-I. et al. (2009) A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. Journal of the Neurological Sciences, 285 (1-2), pp. 67-77 http://dx.doi.org/10.1016/j.jns.2009.05.027
Michelsen, J. (2013) Canine elbow dysplasia: Aetiopathogenesis and current treatment recommendations. The Veterinary Journal, 196 (1), pp. 12-19 http://dx.doi.org/10.1016/j.tvjl.2012.11.009
Fitzpatrick, N. (2009) Radiographic and arthroscopic findings in the elbow joints of 263 dogs with medial coronoid disease. Veterinary Surgery, 38 (2), pp. 213-223 http://dx.doi.org/10.1111/j.1532-950X.2008.00489.x
Meyer-Lindenberg, A. et al. (2002) Prevalence of fragmented medial coronoid process of the ulna in lame adult dogs. Veterinary Record, 151 (8), pp. 230-234. http://dx.doi.org/10.1136/vr.151.8.230
Conzemius, M.G. and Evans, R.B. (2012) Caregiver placebo effect for dogs with lameness from osteoarthritis. Journal of the American Veterinary Medical Association, 241 (10), pp. 1314-1319. http://dx.doi.org/10.2460/javma.241.10.1314
Wucherer, K.L. et al. (2012) The use of delayed gadolinium enhanced magnetic resonance imaging of cartilage and t2 mapping to evaluate articular cartilage in the normal canine elbow. Veterinary Radiology & Ultrasound, 53 (1), pp. 57-63. http://dx.doi.org/10.1111/j.1740-8261.2011.01867.x
Böttcher, P. et al. (2013) Estimation of Joint Incongruence in Dysplastic Canine Elbows Before and After Dynamic Proximal Ulnar Osteotomy. Veterinary Surgery, 42 (4) p. 371 http://dx.doi.org/10.1111/j.1532-950X.2013.01085.x
Fitzpatrick, N. et al. (2013) Bi-oblique dynamic proximal ulnar osteotomy in dogs: Reconstructed computed tomographic assessment of radioulnar congruence over 12 weeks. Veterinary Surgery, 42 (6), pp. 727-738 http://dx.doi.org/10.1111/j.1532-950X.2013.12014.x
Cunningham, T. et al. (2006) Delayed gadolinium-enhanced magnetic resonance imaging of cartilage to predict early failure of Bernese periacetabular osteotomy for hip dysplasia. The Journal of Bone and Joint Surgery (American), 88 (7), pp. 1540-1548. http://dx.doi.org/10.2106/JBJS.E.00572
Burton, N.J. et al. (2011) Conservative Versus Arthroscopic Management for Medial Coronoid Process Disease in Dogs: A Prospective Gait Evaluation. Veterinary Surgery, 40 (8), pp. 972-980. http://dx.doi.org/10.1111/j.1532-950X.2011.00900.x
Evans, R.B. (2008) Comparison of three methods for the management of fragmented medial coronoid process in the dog. A systematic review and meta-analysis. Veterinary and Comparative Orthopaedics and Traumatology, 21, pp. 106-109 http://dx.doi.org/10.3415/VCOT-07-04-0031
Samoy, Y.C. et al. (2013) Arthroscopic treatment of fragmented coronoid process with severe elbow incongruity. Long-term follow-up in eight Bernese Mountain Dogs. Veterinary and Comparative Orthopaedics and Traumatology, 26 (1), pp. 27-33 http://dx.doi.org/10.3415/VCOT-11-06-0087
Samoy, Y.C. et al. (2012) Arthroscopic Findings in 32 Joints Affected by Severe Elbow Incongruity with Concomitant Fragmented Medial Coronoid Process. Veterinary Surgery 41, pp. 355-361. http://dx.doi.org/10.1111/j.1532-950X.2012.00949.x
Vermote, K.A.G. et al. (2010) Elbow lameness in dogs of six years and older: arthroscopic and imaging findings of medial coronoid disease in 51 dogs. Veterinary and Comparative Orthopaedics and Traumatology, 23, pp. 43-50. http://dx.doi.org/10.3415/VCOT-09-03-0032
Kiefer, K.M. et al. (2014) The Influence of Culture Medium Type on Cellular Phenotype of Canine Adipose Derived Stem Cells. 3 (1), pp. 28-37. http://dx.doi.org/10.4236/ojrm.2014.31004
Gorin, N.C. (1978) Long-term preservation of bone marrow and stem cell pool in dogs. Blood, 51 (2), pp. 257-265.
Kiefer, K.M. et al. (2014) The Influence of Culture Medium Type on Cellular Phenotype of Canine Adipose Derived Stem Cells. Open Journal of Regenerative Medicine, 3 (1), pp. 28-37. http://dx.doi.org/10.4236/ojrm.2014.31004
Brown, D.C. and Farrar, J.T. (2010) Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis Dorothy. Journal of the American Veterinary MedicalAssociation, 68 (6), pp. 631-637.
Brown, D.C. et al. (2007) Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis. American Journal of Veterinary Research, 68 (6), pp. 631-637.
Horstman, C.L. et al. (2004) Assessing the efficacy of perioperative oral carprofen after cranial cruciate surgery using noninvasive, objective pressure platform gait analysis. Veterinary Surgery, 33 (3), pp. 286-292. http://dx.doi.org/10.1111/j.1532-950x.2004.04042.x
Feldsien, J.D. et al. (2010) Serum cortisol concentration and force plate analysis in the assessment of pain associated with sodium urate–induced acute synovitis in dogs. American Journal of Veterinary Research. 71(8).
Moreau, M. et al. (2010) Influence of changes in body weight on peak vertical force in osteoarthritic dogs: A possible bias in study outcome. Veterinary Surgery, 39 (1), pp. 43-47. http://dx.doi.org/10.1111/j.1532-950X.2009.00621.x
Rumph, P.F. et al. (1999) Interday variation in vertical ground reaction force in clinically normal Greyhounds at the trot. American Journal of Veterinary Research, 60 (6), pp. 679-683.
License
Veterinary Evidence uses the Creative Commons copyright Creative Commons Attribution 4.0 International License. That means users are free to copy and redistribute the material in any medium or format. Remix, transform, and build upon the material for any purpose, even commercially - with the appropriate citation.
