In dogs diagnosed with osteoarthritis in the hip, elbow, stifle or shoulder joint, is treatment with intra-articular allogenic mesenchymal stem cell therapy, in comparison with a placebo effect, more effective at reducing lameness and pain?
Clinical bottom line
Category of research question
The number and type of study designs reviewed
All three papers were randomised controlled trials
Strength of evidence
Intra-articular allogenic stem cell therapy is effective at reducing pain and lameness in dogs with osteoarthritis when compared to a placebo effect. Two studies indicated a statistically significant improvement in both client and veterinary outcome measurements. Client outcome measurements utilised included: the canine brief pain inventory; a measure of any changes in pain and lameness based on owners perception, and the client-specific outcome measure; and an evaluation of the impact of osteoarthritis on three client selected activities and how this changed with treatment. Veterinary outcome measurements included veterinary pain score based on manipulation of the limb, veterinary assessment of clinical outcomes and veterinary pre and post lameness examinations, all of which were subjective measures.
The final study identified a statistically significant improvement in both pain and lameness based on owner assessments utilising the canine brief pain inventory and the Hudson Visual Analogue Scale for lameness scoring. No statistically significant improvement was identified when considering subjective and objective veterinary measurements including force plate gait analysis and veterinary orthopaedic examination
There is moderate evidence from owner observation and veterinary assessment to suggest that intra-articular allogenic (adipose and umbilical derived) stem cell therapy has some efficacy for reducing pain and lameness compared to a placebo effect. However, it must be noted that these studies did not compare the use of intra-articular allogenic stem cells with conventional treatments such as intra-articular corticosteroid injections. Therefore, comparison trials are required.
Whilst all three papers showed significant improvements in the subjective measurements, objective data outcomes and assessment by board certified veterinary surgeons failed to find a significant improvement in peak vertebral force or lameness with the use of intra-articular stem cell therapy in comparison to a placebo effect. Furthermore, whilst no significant adverse reactions to intra-articular stem cell therapy were recorded, information regarding the safety for multiple dosing is lacking and ambiguity remains as to the most appropriate lineage and quantity of allogenic stem cells for the best clinical effect
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Brown, D., Boston, R.C., Coyne, J.C. & Farrar, J.T. (2008). Ability of the Canine Brief Pain Inventory to detect response to treatment in dogs with osteoarthritis. [online]. Available at: https://www.CanineBPI.com [Accessed 6 Jan 2022].
Harman, R., Carlson, K., Gaynor, J., Gustafson, S., Dhupa, S., Clement, K., Hoelzler, M., McCarthy, T., Schwartz, P. & Adams, C. (2016). A Prospective, Randomized, Masked, and Placebo-Controlled Efficacy Study of Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis in Dogs. Frontiers in Veterinary Science. 3, 16. DOI: https://doi.org/10.3389/fvets.2016.00081
Hass, R., Kasper, C., Böhm, S. & Jacobs, R. (2011). Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Communication and Signalling - BioMed Central. 9(12). DOI: https://doi.org/10.1186/1478-811X-9-1
Hudson, J.T., Slater, M.R., Taylor, L., Scott, H.M. & Kerwin, S.C. (2004). Assessing repeatability and validity of a visual analogue scale questionnaire for use in assessing pain and lameness in dogs. American Journal of Veterinary Research. 65(12), 1634–1643. DOI: https://doi.org/10.2460/ajvr.2004.65.1634
Khaddour, K., Hana, C.K. & Mewawalla, P. (2020). Hematopoietic Stem Cell Transplantation - StatPearls - NCBI Bookshelf. StatPearls.[online]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK536951/ [Accessed 10 Jan 22].
Kim, S.E., Pozzi, A., Yeh, J.C., Lopez-Velazquez, M., Au Yong, J.A., Townsend, S., Dunlap, A.E., Christopher, S.A., Lewis, D.D., Johnson, M.D. & Petrucci, K. (2019). Intra-Articular Umbilical Cord Derived Mesenchymal Stem Cell Therapy for Chronic Elbow Osteoarthritis in Dogs: A Double-Blinded, Placebo-Controlled Clinical Trial. Frontiers in Veterinary Science. 6(December), 1–10. DOI: https://doi.org/10.3389/fvets.2019.00474
Maki, C.B., Spaas, J.H., Camiel Alice Samoy, Y., Fahie, M., C-bcc, W., Beck, A., Cheuk Chi Wallis, C.-B., Choo, J., Ramos, T., Tong, R., Borjesson, D.L. & Izadyar, F. (2020). Intra-articular Administration of Allogeneic Adipose Derived MSCs Reduces Pain and Lameness in Dogs With Hip Osteoarthritis: A Double Blinded, Randomized, Placebo Controlled Pilot Study. Frontiers in Veterinary Science. 1, 570. DOI: https://doi.org/10.3389/fvets.2020.00570
McLaughlin, R.M. (2001). Kinetic and Kinematic Gait Analysis in Dogs. The Veterinary Clinics of North America : Small Animal Practice. 31(1), 193–201. DOI: https://doi.org/10.1016/S0195-5616(01)50045-5
Michálek, J., Collins, R.H., Hill, B.J., Brenchley, J.M., Douek, D.C. (2003). Identification and monitoring of graft-versus-host specific T-cell clone in stem cell transplantation. The Lancet. 361 (9364), 1183–1185. DOI: https://doi.org/10.1016/S0140-6736(03)12917-0
Pettitt, R.A. & German, A.J. (2015). Investigation and management of canine osteoarthritis. In Practice. DOI: https://doi.org/10.1136/inp.h5763
(2021). RVC Canine Stem Cell Treatments Owners' Frequently Asked Questions. [online]. Available at: https://www.rvc.ac.uk/small-animal-vet/specialist-referrals/advanced-techniques/stem-cell-clinic/information-for-dog-owners#panel-will-my-dog-be-treated-with-stem-cells-from-other-dogs [Accessed 24 Jan 2022].
Singh, J.A. (2012). Stem cells and other innovative intra-articular therapies for osteoarthritis: What does the future hold? BMC Medicine. 44. DOI: https://doi.org/10.1186/1741-7015-10-44
Suresh, K., Chandrashekara, S. (2012). Sample size estimation and power analysis for clinical research studies. Journal of Human Reproductive Sciences. 5(1), 7-13. DOI: https://doi.org/10.4103/0974-1208.97779
Wi, H., Lee, S., Kim, Y., No, J.G., Lee, P., Lee, B.R., Oh, K.B., Hur, T.Y. & Ock, S.A. (2021). Immunosuppression-enhancing effect of the administration of allogeneic canine adipose-derived mesenchymal stem cells(cA-MSCs) compared with autologous cA-MSCs in vitro. Journal of Veterinary Science. 22(5), 1–14. DOI: https://doi.org/10.4142/JVS.2021.22.E63
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