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

Jose M Carrillo¹  Joaquín Sopena¹  Ramón Cugat³  Mónica Rubio²  Belén Cuervo¹  Angelo Santana⁴  Manuel Morales⁴  Miguel Batista⁴  Jose M Vilar⁴ 

[1] Garcia Cugat Foundation-UCH Chair, Barcelona, Spain;Instituto de Ciencias Biomédicas Universidad CEU Cardenal Herrera, C/del pozo s/n, Alfara del Patriarca, Valencia 46115, Spain;Artroscopia GC, Hospital Quirón Barcelona, Plaza Alfonso Comí, 12, Barcelona, Spain;Department of Animal Pathology, Faculty of Veterinary Medicine, Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas, 35413 Las Palmas, Spain

关键词: Force platform;    MSC;    Adipose-derived mesenchymal stem cells;    Hip;    Osteoarthrosis;   

Others  :  866273
DOI  :  10.1186/1746-6148-10-143

 received in 2013-12-16, accepted in 2014-06-19,  发布年份 2014

【 摘 要 】

Background

Regenerative medicine using Mesenchymal Stem Cells (MSC) alone or combined with Plasma Rich in Growth Factors (PRGF) is a rapidly growing area of clinical research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify and quantify the efficacy of different therapeutic strategies for the treatment of OA in dogs including MSC associated to PRGF, but never with AD-MSC alone.

The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA.

Results

Ten lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved within the first three months post-treatment in the OA group, increasing 9% and 2.5% body weight, respectively, at day 30. After this, the effect seems to decrease reaching initial values.

Conclusion

Intraarticular ADMSC therapy objectively improved limb function in dogs with hip OA. The duration of maximal effect was less than 3 months.

【 授权许可】

   
2014 Vilar et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Bockstahler B, Krautler C, Holler P, Kotschwar A, Vobornik A, Peham C: Pelvic limb kinematics and surface electromyography of the vastus lateralis, biceps femoris, and gluteus medius muscle in dogs with hip osteoarthritis. Vet Surg 2012, 41:54-62.
• [2]Silvestre AM, Ginja MM, Ferreira AJ, Colaço J: Comparison of estimates of hip dysplasia genetic parameters in Estrela Mountain dog using linear and threshold models. J Anim Sci 2007, 85:1880-1884.
• [3]Maldonado M, Nam J: The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int 2013. http://dx.doi.org/10.1155/2013/284873 webcite
• [4]Oldershaw R: Cell sources for the regeneration of articular cartilage: the past, the horizon and the future. Int Exp Path 2012, 93:389-400.
• [5]Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL: Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. Vet Comp Orthop TraumatolIn press
• [6]Vilar JM, Morales M, Santana A, Spinella G, Rubio M, Cuervo B, Cugat R, Carrillo JM: 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 Vet Res 2013, 9:131. BioMed Central Full Text
• [7]Takemitsu H, Zhao D, Yamamoto I, Harada Y, Michishita M, Arai T: Comparison of bone marrow and adipose tissue-derived canine mesenchymal stem cells. BMC Vet Res 2012, 8:150. BioMed Central Full Text
• [8]Guercio A, Di Marco P, Casella S, Cannella V, Russotto L, Purpari G, Di Bella S, Piccione G: Production of canine mesenchymal stem cells from adipose tissue and their application in dogs with chronic osteoarthritis of the humeroradial joints. Cell Biol Int 2012, 36:189-94.
• [9]Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, Toda K: Mobilization of bone marrow-derived mesenchymal stem cells into theinjured tissues after intraarticular injection and their contribution to tissueregeneration. Knee Surg Sports Traumatol Arthrosc 2006, 14:1307-1314.
• [10]Harman R, Cowles B, Orava C: A retrospective review of 62 cases of suspensory ligament injury insport horses treated with adipose-derived stem and regenerative cell therapy. In Proceedings of the Veterinary Orthopedic Society. Veterinary Orthopedic Society: Keystone; 2006:212-214.
• [11]Dahlgren LA: Use of adipose derived stem cells in tendon and ligament injuries. In Proceedings of the American College of Veterinary Surgeons Symposium Equine and Small Animal. Washington: American College of Veterinary Surgeons; 2006:150-151.
• [12]Nixon A, Dahlgren L, Haupt J, Yeager AE, Ward DL: Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis. Am J Vet Res 2008, 69:928-937.
• [13]Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, Gingerich DA, Harman R: 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. Vet Ther 2007, 8:272-84.
• [14]Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R, Harman S, Gingerich DA, Harman R: 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. Vet Ther 2008, 9:192-200.
• [15]Ball SG, Shuttleworth A, Kielty CM: Inhibition of platelet-derived growth factor receptor signaling regulates Oct4 and Nanog expression, cell shape, and mesenchymal stem cell potency. Stem Cells 2012, 30:548-60.
• [16]Rodríguez FJ, Valdés T, Carrillo JM, Rubio M, Monleon M, García DM, García M, Cugat R, Moreno V: Platelet-rich plasma favors proliferation of canine adipose-derived mesenchymal stem cells in methacrylate-endcapped caprolactone porous scaffold niches. J Funct Biomater 2012, 3:556-568.
• [17]Bennett RL, DeCamp CE, Flo GL, Hauptman JG, Stajich M: Kinematic gait analysis in dogs with hip dysplasia. Am J Vet Res 1996, 7:966-971.
• [18]Poy NS, DeCamp CE, Bennett RL, Hauptman JG: Additional kinematic variables to describe differences in the trot between clinically normal dogs and dogs with hip dysplasia. Am J Vet Res 2000, 8:974-978.
• [19]Gordon WJ, Conzemius MG, Riedesel E, Besancon MF, Evans R, Wilke V, Ritter MJ: The relationship betweenlimb function and radiographic osteoarthrosis in dogs with stifle osteoarthrosis. Vet Surg 2003, 32:451-454.
• [20]Voss K, Imhof J, Kaestner S, Montavon PM: Force plate gaitanalysis at the walk and trot in dogs with low-grade hindlimb lameness. Vet Comp Orthop Traumatol 2007, 20:299-304.
• [21]Evans R, Gordon W, Conzemius M: Effect of velocity on ground reaction forces in dogs with lameness attributable to tearing of the cranial cruciate ligament. Am J Vet Res 2003, 64:1479-1481.
• [22]Vilar JM, Morales M, Santana A, Batista M, Miró F, Spinella G: Long-term valuation of oral mavacoxib in Osteoarthrosic dogs using force platform analysis. Pak Vet J 2013, 33:229-233.
• [23]Moreau M, Lussier B, Doucet M, Vincent G, Martel-Pelletier J, Pelletier JP: Efficacy of licofelone in dogs with clinical osteoarthritis. Vet Rec 2007, 160:584-588.
• [24]Bennett RL, DeCamp CE, Flo GL, Hauptman JG, Stajich M: Kinematic gait analysis in dogs with hip dysplasia. Am J Vet Res 1996, 57:966-71.
• [25]DeCamp CE, Riggs CM, Olivier NB, Hauptman JG, Hottinger HA, Soutas-Little RW: Kinematic evaluation of gait in dogs with cranial cruciate ligament rupture. Am J Vet Res 1996, 57:120-126.
• [26]Budsberg SC, Johnston SA, Schwarz PD, DeCamp CE, Claxton R: Efficacy of etodolac for the treatment of osteoarthritis of the hip joints in dogs. J Am Vet Med Assoc 1999, 214:206-210.
• [27]Bigham-Sadegh A, Mirshokraei P, Karimi I, Oryan A, Aparviz A, Shafiei-Sarvestani Z: Effects of adipose tissue stem cell concurrent with greater omentum on experimental long-bone healing in dog. Connect Tissue Res 2012, 53:334-342.
• [28]Haghighat A, Akhavan A, Hashemi-Beni B, Deihimi P, Yadegari A, Heidari F: Adipose derived stem cells for treatment of mandibular bone defects: an autologous study in dogs. Dent Res J (Isfahan) 2011, 8(Suppl1):51-57.
• [29]Kang BJ, Ryu HH, Park SS, Koyama Y, Kikuchi M, Woo HM, Kim WH, Kweon OK: Comparing the osteogenic potential of canine mesenchymal cells derived from adipose tissues, bone marrow, umbilical cord blood, and wharton’s jelly for treating bone defects. J Vet Sci 2012, 13:299-310.
• [30]Oh HJ, Park EJ, Lee SY, Soh JW, Kong IS, Choi SW, Ra JC, Kang SK, Lee BC: Comparison of cell proliferation and epigenetic modification of gene expression patterns in canine foetal fibroblasts and adipose tissue-derived mesenchymal stem cells. Cell Prolif 2012, 45:438-444.
• [31]Murphy JM, Fink DJ, Hunziker EB, Barry FP: Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 2003, 48:3464-3474.
• [32]Vogel PL: Surgeon’s use of adipose stem cell therapy [abstract]. Vet Comp Orthop Traumatol 2012, 3:10.
• [33]Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi YJ: Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 2013, 29:748-755.
• [34]Pinheiro J, Bates D: Fitting linear mixed-effects models. In Mixed-effects models in S and S-PLUS. 1st edition. Edited by Chambers J. New York: Springer-Verlag; 2000:133-197.
• [35]Milliken GA, Johnson DE: Analysis of mixed models/case studies of a mixed model. In Analysis of Messy Data, Volume 1. 2nd edition. Florida: Chapman and Hall; 2009:385-417.
• [36]Certificate for hip and elbow dysplasia http://www.fci.be/uploaded_files/77-2001.pdf webcite
• [37]Piermattei D, Flo G, DeCamp C: Orthopedic examination and diagnostic tools. In Brinker, Piermattei and Flo’s Handbook of Small Orthopedics and Fracture Repair. 4th edition. Edited by Fathman L. Missoury: Saunders; 2006:3-24.
• [38]R Development Core Team: R: A language and environment for statistical computing. http://www.R-project.org/ webcite