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Guerra-Gomes M, Ferreira-Baptista C, Barros J, Alves-Pimenta S, Gomes P, Colaço B. Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals. Animals (Basel) 2025; 15:589. [PMID: 40003071 PMCID: PMC11851989 DOI: 10.3390/ani15040589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/07/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being a prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of emerging therapies showing potential to alleviate symptoms and promote joint health. Among these, hyaluronic acid and platelet-rich plasma have been widely used as intra-articular treatments to enhance joint lubrication, reduce inflammation, and provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, and autologous protein solution represent the next generation of regenerative therapies, offering more disease-modifying effects by inhibiting key mediators of joint inflammation. More recently, the MSC-derived secretome has emerged as an innovative, cell-free approach that leverages the diverse bioactive factors secreted by MSCs to support tissue repair and modulate inflammation. This review highlights the evidence base behind these non-cellular orthobiologic treatments for stifle joint disease, aiming to inform veterinary practitioners and owners about available options and their efficacy in supporting conventional treatments.
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Affiliation(s)
- Maria Guerra-Gomes
- i3S—Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (M.G.-G.); (J.B.)
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Carla Ferreira-Baptista
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Joana Barros
- i3S—Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (M.G.-G.); (J.B.)
| | - Sofia Alves-Pimenta
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Pedro Gomes
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Bruno Colaço
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
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Perego R, Meroni G, Martino PA, Spada E, Baggiani L, Proverbio D. Antibacterial Effect of Canine Leucocyte Platelet-Rich Plasma (L-PRP) and Canine Platelet-Poor Plasma (PPP) Against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus pseudintermedius. Vet Sci 2024; 11:670. [PMID: 39729010 DOI: 10.3390/vetsci11120670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/18/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024] Open
Abstract
Staphylococcus pseudintermedius (SP) is a commensal and opportunistic pathogen of skin and mucosal surfaces, isolated from healthy dogs and from canine pyoderma cases. It has recently gained attention due to its increasing antibiotic resistance. Platelet-rich plasma (PRP) is a biological product, obtained through a blood centrifugation process, which has antibacterial properties evidenced by in vitro and in vivo studies conducted in both the human and veterinary field. This in vitro study evaluated the antimicrobial effect of canine non-activated and activated leucocyte-rich PRP (L-PRP) and platelet-poor plasma (PPP) against two strains of SP isolated from dogs with pyoderma: one a multidrug-resistant strain (MDR) and one a non-MDR strain. Twenty healthy un-sedated adult blood donor dogs were enrolled for L-PRP and PPP production via a closed semi-automatic system for veterinary use. The evaluation of antimicrobial effect was performed using the micro-inhibition in broth method, exposing SP strains to 10 L-PRP, 10 activated L-PRP and 10 PPP samples, respectively. Bacterial growth was evaluated using CFU count at three timepoints (immediately after incubation T0, after 1 h T1 and after 2 h T2). L-PRP and PPP had a significant antimicrobial effect at all three timepoints which was similar against both non-MDR and MDR SP strains. Activation appeared to reduce the duration of the antimicrobial effect in L-PRP. More studies are necessary to confirm these preliminary results.
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Affiliation(s)
- Roberta Perego
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell'Università 6, 26900 Lodi, Italy
| | - Gabriele Meroni
- One Health Unit, Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Italy
| | - Piera Anna Martino
- One Health Unit, Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Italy
| | - Eva Spada
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell'Università 6, 26900 Lodi, Italy
| | - Luciana Baggiani
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell'Università 6, 26900 Lodi, Italy
| | - Daniela Proverbio
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell'Università 6, 26900 Lodi, Italy
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Alves JC, Santos A, Filipe A, Carreira LM. The intravenous administration of blood cell secretome can improve clinical signs in dogs with osteoarthritis. Res Vet Sci 2024; 180:105422. [PMID: 39348758 DOI: 10.1016/j.rvsc.2024.105422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 08/25/2024] [Accepted: 09/23/2024] [Indexed: 10/02/2024]
Abstract
We aimed to evaluate the effect of the intravenous (IV) administration of blood cell secretome (BCS) compared to its intra-articular (IA) administration. In this cross-over study, ten dogs with bilateral hip osteoarthritis were initially assigned to an IA group (IAG). After a 180-day follow-up, the same 10 animals were assigned to an IV group (IVG). IAG received a single IA administration of 3 ml of BCS per hip joint, and IVG received a single 6 ml IV administration of BCS. Following each treatment, follow-up was conducted on days 0, 8, 15, 30, 60, 90, 120, 150, and 180. In each follow-up, copies of the Canine Brief Pain Inventory (divided into pain interference score - PIS and Pain Severity Score - PSS), Liverpool Osteoarthritis in Dogs (LOAD), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) were obtained. Results were analyzed with the Mann-Whitney test, and Kaplan-Meier estimators were calculated and compared, p < 0.05. The animals had a mean age of 7.6 ± 2.9 years and bodyweight of 27.8 ± 3.6 kg. Seven hips were classified as moderate osteoarthritis, and three as severe. No differences were found between groups from days 0 to +60d, with both groups showing clinically significant improvements. Improvements in the IAG lasted up to +120d. Kaplan-Meier estimators showed that dogs in IAG took longer to record the considered events. IVG also showed positive clinically significant results with different instruments. IV administration of BCS can improve the overall condition of dogs with hip OA, but the IA administration produces longer-lasting results.
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Affiliation(s)
- J C Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR). Rua Presidente Arriaga, 9 1200-771 Lisbon, Portugal; Faculty of Veterinary Medicine, Lusófona University, Lisbon, Portugal; CECAV - Animal and Veterinary Research Center, Lusófona University, Lisbon, Portugal; MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554 Évora, Portugal.
| | - A Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR). Rua Presidente Arriaga, 9 1200-771 Lisbon, Portugal
| | - Ana Filipe
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal
| | - L Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa) -, Lisbon, Portugal; Interdisciplinary Centre for Research in Animal Health (CIISA) - University of Lisbon, (FMV/ULisboa) - Lisbon, Portugal; Anjos of Assis Veterinary Medicine Centre (CMVAA), Barreiro, Portugal
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Zhang JY, Xiang XN, Yu X, Liu Y, Jiang HY, Peng JL, He CQ, He HC. Mechanisms and applications of the regenerative capacity of platelets-based therapy in knee osteoarthritis. Biomed Pharmacother 2024; 178:117226. [PMID: 39079262 DOI: 10.1016/j.biopha.2024.117226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 08/25/2024] Open
Abstract
Osteoarthritis (OA) is the most prevalent joint disease in the elderly population and its substantial morbidity and disability impose a heavy economic burden on patients and society. Knee osteoarthritis (KOA) is the most common subtype of OA, which is characterized by damage to progressive articular cartilage, synovitis, and subchondral bone sclerosis. Most current treatments for OA are palliative, primarily aim at symptom management, and do not prevent the progression of the disease or restore degraded cartilage. The activation of α-granules in platelets releases various growth factors that are involved in multiple stages of tissue repair, suggesting potential for disease modification. In recent years, platelet-based therapies, such as platelet-rich plasma, platelet-rich fibrin, and platelet lysates, have emerged as promising regenerative treatments for KOA, but their related effects and mechanisms are still unclear. Therefore, this review aims to summarize the biological characteristics and functions of platelets, classify the products of platelet-based therapy and related preparation methods. Moreover, we summarize the basic research of platelet-based regeneration strategies for KOA and discuss the cellular effects and molecular mechanisms. Further, we describe the general clinical application of platelet-based therapy in the treatment of KOA and the results of the meta-analysis of randomized controlled trials.
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Affiliation(s)
- Jiang-Yin Zhang
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xiao-Na Xiang
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xi Yu
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Yan Liu
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Hong-Ying Jiang
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Jia-Lei Peng
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Cheng-Qi He
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Hong-Chen He
- Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China.
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Bergström A, Kjörk Granström M, Roepstorff L, Alipour MJ, Pettersson K, Ljungvall I. Long-Term Effect of Intra-Articular Adipose-Derived Stromal Vascular Fraction and Platelet-Rich Plasma in Dogs with Elbow Joint Disease-A Pilot Study. Vet Sci 2024; 11:296. [PMID: 39057980 PMCID: PMC11281594 DOI: 10.3390/vetsci11070296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
(1) Background: The aim of the current pilot study was to describe the long-term effects of a single intra-articular injection of autologous stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in dogs with confirmed elbow OA, using orthopedic lameness scoring and kinetic and kinematic gait analysis. For comparison of normal long-term variation of gait over time, a group of healthy control dogs (CDs) was also evaluated. (2) Methods: A prospective longitudinal clinical pilot study investigating 19 client-owned dogs with elbow OA (OADs) treated with SVF and PRP and eight CDs not receiving treatment. The OAD and CD groups were evaluated before and after 6 and at least 12 months following treatment with SVF and PRP (OAD group) and twice with a six-month interval (CD group), respectively, through orthopedic examinations, goniometry, and kinetic and kinematic analyses (seven variables). (3) Results: The OAD had an increase in fore-hind peak force symmetry ≥12 months after treatment (p < 0.05), but no other objective variables changed over time. Orthopedic consensus scores had improved at ≥six months follow-up evaluation (p < 0.05). None of the investigated gait variables had changed at ≥six months follow-up evaluation in the CD group. (4) Conclusions: The current study could not confirm a significant benefit from SVF and PRP treatment in OADs, but future studies should be conducted in order to fully evaluate the potential of the treatment. The improvement seen in fore-hindlimb symmetry may represent an improvement in gait or an incidental finding.
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Affiliation(s)
- Annika Bergström
- Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, P.O. Box 7070, 75007 Uppsala, Sweden; (A.B.); (I.L.)
| | - Miriam Kjörk Granström
- University Animal Hospital, Swedish University of Agricultural Sciences, Ultunaallén 5A, P.O. Box 7070, 75007 Uppsala, Sweden;
| | - Lars Roepstorff
- Department of Anatomy, Physiology and Biochemistry, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, P.O. Box 7070, 75007 Uppsala, Sweden;
| | - Mohammad J. Alipour
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Agnes Sjöberginkatu 2, P.O. Box 66, 00014 Helsinki, Finland;
| | - Kjerstin Pettersson
- University Animal Hospital, Swedish University of Agricultural Sciences, Ultunaallén 5A, P.O. Box 7070, 75007 Uppsala, Sweden;
| | - Ingrid Ljungvall
- Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, P.O. Box 7070, 75007 Uppsala, Sweden; (A.B.); (I.L.)
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Volz F, Eberle D, Kornmayer M, Zablotski Y, Meyer-Lindenberg A. Effect of intra-articular platelet-rich plasma or hyaluronic acid on limb function recovery in dogs with TPLO for cranial cruciate ligament rupture: a randomised controlled trial. J Small Anim Pract 2024; 65:223-233. [PMID: 38339913 DOI: 10.1111/jsap.13704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 11/17/2023] [Accepted: 01/01/2024] [Indexed: 02/12/2024]
Abstract
OBJECTIVES This study aimed to investigate the recovery of limb function following a single intra-articular injection of platelet-rich plasma or hyaluronic acid in dogs with cranial cruciate ligament rupture treated with tibial plateau levelling osteotomy compared to dogs receiving no injection intraoperatively. MATERIALS AND METHODS Sixty-two dogs with cranial cruciate ligament rupture, body weights of 20 to 40 kg, and no other orthopaedic conditions were enrolled in this prospective, randomised, double-blind, controlled study at the small animal clinic at LMU Munich. All dogs underwent tibial plateau levelling osteotomy. Based on random allocation, they received either a single intra-articular injection of platelet-rich plasma, hyaluronic acid or no injection intraoperatively. Gait analysis, clinical examinations, radiography of the stifle joint for osteoarthritis progression and two validated owner questionnaires were compared among groups at three timepoints postoperatively (6 weeks, 3 and 6 months). Limb function was primarily assessed by measuring the ground reaction forces. RESULTS At all times postoperatively, no differences were observed among groups regarding clinical examinations, osteoarthritis score values, ground reaction forces or owner questionnaires. All dogs showed significant improvement in limb function clinically, in all ground reaction forces and in the validated questionnaires. Osteoarthritis progressed minimally during rechecks in all dogs regardless of the additional injection or not. CLINICAL SIGNIFICANCE All dogs treated with tibial plateau levelling osteotomy for cranial cruciate ligament rupture showed improvements in limb function. No additive effect on faster recovery was demonstrated with the additional intra-articular injection of platelet-rich plasma or hyaluronic acid. Addition of platelet-rich plasma/hyaluronic acid injections during tibial plateau levelling osteotomy is unnecessary considering the lack of benefit observed up to 6 months postoperatively.
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Affiliation(s)
- F Volz
- Clinic for Small Animal Surgery and Reproduction, Ludwig-Maximilians-University, Munich, Germany
| | - D Eberle
- Clinic for Small Animal Surgery and Reproduction, Ludwig-Maximilians-University, Munich, Germany
| | - M Kornmayer
- Clinic for Small Animal Surgery and Reproduction, Ludwig-Maximilians-University, Munich, Germany
| | - Y Zablotski
- Clinic for Small Animal Surgery and Reproduction, Ludwig-Maximilians-University, Munich, Germany
| | - A Meyer-Lindenberg
- Clinic for Small Animal Surgery and Reproduction, Ludwig-Maximilians-University, Munich, Germany
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Scharpf M, Theyse LFH. Assessment of Outcome of Arthroscopic Subtotal Coronoidectomy in Treating Medial Coronoid Disease and Effect of Concurrent Autologous Conditioned Plasma in Dogs Using Force Plate Analysis. Vet Comp Orthop Traumatol 2024; 37:83-89. [PMID: 37967845 DOI: 10.1055/s-0043-1776785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2023]
Abstract
OBJECTIVE The aim of this study was to assess the outcome of arthroscopic subtotal coronoidectomy in treating medial coronoid disease and the effect of concurrent autologous conditioned plasma (ACP) in dogs using force plate analysis. STUDY DESIGN This study included 16 dogs with unilateral medial coronoid disease based on computed tomographic imaging. Treatment consisted of an arthroscopic subtotal coronoidectomy. As concurrent therapy, eight dogs received ACP at the end of the arthroscopy and eight dogs a placebo. Force plate analysis, including vertical forces, braking and propulsive forces, corresponding impulses and symmetry indices, was performed prior to arthroscopy and at 4, 12 and 26 weeks postoperatively. RESULTS After an initial reduction of all force plate analysis parameters, vertical and propulsive parameters gradually improved to the level of healthy dogs at 26 weeks postoperatively. In contrast, braking parameters did not reach normal values at 26 weeks, demonstrating ongoing loss of elbow joint function. The ACP and placebo group did not show any significant difference in force plate analysis parameters during the 26 weeks study period. CONCLUSION Arthroscopic subtotal coronoidectomy did not result in complete normalization of ground reaction forces, impulses and symmetry indices. Concurrent treatment with ACP, immediately after arthroscopy, did not improve outcome. Our results show that outcome of arthroscopic subtotal coronoidectomy in treating medial coronoid disease is less favourable than previously reported.
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Affiliation(s)
- Marlene Scharpf
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Soft Tissue and Orthopaedic Surgery Service, Leipzig, Germany
| | - Lars F H Theyse
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Soft Tissue and Orthopaedic Surgery Service, Leipzig, Germany
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Bharti D, Ajith Y, Sharun K, Banu SA, Kumar A, Bhardwaj A, Sidar SK, Dhaleshwari. Therapeutic applications of canine platelets and their derivatives: a narrative review. Top Companion Anim Med 2024; 58:100840. [PMID: 37979613 DOI: 10.1016/j.tcam.2023.100840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/02/2023] [Accepted: 11/13/2023] [Indexed: 11/20/2023]
Abstract
Platelets contain a multitude of growth factors and play a crucial role in physiological processes such as thrombogenesis, tissue repair, and angiogenesis. As a result, platelet-derived products have significant potential for efficient utilization in the realm of regenerative medicine due to their therapeutic and biological attributes. Numerous studies have already substantiated the therapeutic viability of platelets in various canine ailments. The existing literature indicates a substantial surge in the clinical application of canine platelets, positioning platelet-derived products as a viable alternative to conventional therapeutic agents. Platelet concentrates, including platelet-rich plasma and platelet-rich fibrin are commonly used as a therapeutic modality in clinical cases. These therapeutic derivatives exhibit effectiveness in tissue regeneration and can serve as complementary therapies. Notably, they offer a cost-effective and easily accessible therapeutic option, which has demonstrated its benefits in chronic inflammatory disorders such as osteoarthritis and tendinitis, ophthalmic conditions, wound healing, and mandibular injuries in canine patients. The broad spectrum of therapeutic effects displayed by platelets is providing researchers with novel perspectives for crafting therapeutic models in future investigations. This review centers on exploring the therapeutic potential of canine platelets across diverse disorders. Further exploration into platelet products, encompassing their preparation and applicability in canine medicine, is imperative. These inquiries hold the promise of unveiling fresh horizons for the domain of regenerative medicine.
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Affiliation(s)
- Deeksha Bharti
- Department of Veterinary Medicine, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar, Udham Singh Nagar, Uttarakhand 263145, India
| | - Y Ajith
- Teaching Veterinary Clinical Complex, College of Veterinary and Animal Sciences, Kerala Veterinary and Animal Sciences University, Mannuthy, Thrissur, Kerala 680651, India.
| | - Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243122, India
| | - S Amitha Banu
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243122, India
| | - Akshay Kumar
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243122, India
| | - Abhishek Bhardwaj
- Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab 141012, India
| | - Shiv Kumar Sidar
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243122, India
| | - Dhaleshwari
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh 243122, India
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Alves JC, Santos A, Carreira LM. A Preliminary Report on the Combined Effect of Intra-Articular Platelet-Rich Plasma Injections and Photobiomodulation in Canine Osteoarthritis. Animals (Basel) 2023; 13:3247. [PMID: 37893971 PMCID: PMC10603638 DOI: 10.3390/ani13203247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/13/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023] Open
Abstract
Osteoarthritis (OA) is highly prevalent in the canine population. Due to the multiple dimensions of the disease, a multimodal approach is usually favored by clinicians. To evaluate the combined treatment with intra-articular platelet-rich plasma (PRP) and photobiomodulation in dogs with bilateral hip OA, thirty dogs were assigned to a PRP group (PRPG, n = 10), a photobiomodulation group (PBMTG, n = 10), or a combined therapies group (PRP+PBMTG, n = 10). The PRPG received two intra-articular administrations of platelet-rich plasma 14 days apart. The PBMTG received photobiomodulation with a therapeutic laser, with three sessions every other day in week one; two sessions in week two; a single session in week three; and one session/month on follow-up evaluation days. The PRP+PBMTG received the two combined therapies. The response to treatment was evaluated with weight-bearing distribution and the Canine Brief Pain Inventory, the Liverpool Osteoarthritis in Dogs, and the Canine Orthopedic Index. Evaluations were conducted before treatment and +8, +15, +30, +60, and +90 days after initial treatment. Normality was assessed with a Shapiro-Wilk test, and the groups' results in each evaluation moment were compared using a Mann-Whitney U test. Animals of both sexes (male n = 19, female n = 11) were included in the sample, with a mean age of 7.8 ± 2.5 years and a body weight of 26.5 ± 4.7 kg. Joints were classified as mild (n = 6, three in PRPG, two in PBMTG, and one in PRP+PBMTG), moderate (n = 18, six in PRPG, five in PBMTG, and seven in PRP+PBMTG), and severe (n = 6, one in PRPG, three in PBMTG, and two in PRP+PBMTG). No differences were found between groups at the initial evaluation. All treatments produced clinically significant improvements compared to the assessment on treatment day. The combination of PRP and photobiomodulation produced greater, longer-lasting improvements. PRP and photobiomodulation can improve objective outcomes and client-reported outcome measures in dogs with OA. Their combined use leads to greater, longer-lasting, clinically significant improvements.
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Affiliation(s)
- J. C. Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal
- Faculty of Veterinary Medicine, Lusófona University, 1749-024 Lisbon, Portugal
- Centro de Ciência Animal e Veterinária, Lusófona University, 1749-024 Lisbon, Portugal
- MED—Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554 Évora, Portugal
| | - Ana Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal
| | - L. Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), 1300-477 Lisbon, Portugal;
- Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV/ULisboa), 1649-004 Lisbon, Portugal
- Anjos of Assis Veterinary Medicine Centre (CMVAA), 2830-077 Barreiro, Portugal
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Palagiano P, Graziano L, Scarabello W, Berni P, Andreoli V, Grolli S. Platelet- Rich Plasma Treatment Supported by Ultrasound Detection of Septa in Recurrent Canine Aural Hematoma: A Case Series. Animals (Basel) 2023; 13:2456. [PMID: 37570265 PMCID: PMC10417061 DOI: 10.3390/ani13152456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Aural hematoma is a common pathological condition in veterinary practice with a high incidence rate in dogs. Drainage, corticosteroid injections, and surgical approaches represent the common treatments in these clinical cases. However, surgery leaves visible signs and is usually correlated with recurrence, scars, and deformation of the treated pinna. For this reason, more effective and less invasive methods have been proposed over the years. Platelet-Rich Plasma (PRP) is one of the most promising options due to its pro-regenerative properties and capability to modulate the inflammatory state. The present work reports 12 cases of canine aural hematoma treated with PRP. The PRP treatment was combined with an ultrasound evaluation of the pinna to detect and treat all involved septa. The results show that relatively large volumes (2 mL) of PRP associated with an ultrasound guide are safe and efficacious in the treatment of canine aural hematoma requiring a maximum of two infiltrations, both in acute and chronic conditions. All the patients recovered their normal ear thickness (compared with the controlateral one) without relapses, averaging 38.5 days from their first treatment (10-90 days; SD: 24.7). The key role of PRP combined with a tailored diagnosis process carried out by the veterinarian, which included using an ultrasound system and the proper bandage, suggests that this approach may represent a valid alternative to surgery and corticosteroids.
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Affiliation(s)
| | - Lisa Graziano
- Clinica Veterinaria Meda, 20821 Meda, Italy; (P.P.); (L.G.)
| | | | - Priscilla Berni
- Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, 43126 Parma, Italy; (P.B.); (S.G.)
| | - Valentina Andreoli
- Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, 43126 Parma, Italy; (P.B.); (S.G.)
| | - Stefano Grolli
- Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, 43126 Parma, Italy; (P.B.); (S.G.)
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11
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Aryazand Y, Buote NJ, Hsieh Y, Hayashi K, Rosselli D. Multifactorial assessment of leukocyte reduced platelet rich plasma injection in dogs undergoing tibial plateau leveling osteotomy: A retrospective study. PLoS One 2023; 18:e0287922. [PMID: 37390083 PMCID: PMC10313002 DOI: 10.1371/journal.pone.0287922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 06/15/2023] [Indexed: 07/02/2023] Open
Abstract
This study assessed the effects of concurrent intra-articular injection and Tibial Plateau Leveling Osteotomy (TPLO) plate surface treatment with leukoreduced platelet rich plasma (lPRP) on outcomes of dogs undergoing TPLO. A retrospective study of medical records for cases presenting from January 2018 to December 2020 was performed. Client-owned dogs with naturally occurring cranial cruciate ligament rupture that underwent TPLO surgery were divided into two groups. The lPRP group included cases that underwent intra-articular injection and plate surface treatment at the time of their TPLO. The control group (C) underwent TPLO without PRP treatment. Data analyzed included: presence of surgical site infection, implant removal rate, degree of change in OA progression score, lameness score progression and radiographic bone healing. The short- and long-term complication rate, hospitalization and antibiotic therapy were also compared between the groups. Descriptive statistics, comparison analyses (Chi square test, t-test, Fisher's exact test) and multi-level logistic regression models were used for statistical analysis. A total of 110 cases met the study inclusion criteria: 54 = lPRP, 56 = C. There were no significant differences between groups with regard to gender, age, presence of meniscal tear, weight, or body condition score. Significant findings included: improved radiographic healing of the osteotomy in the lPRP group, improved global OA scores in the lPRP group, and improved lameness score at recheck examination in the lPRP group. There was no significant difference between the lPRP and C group with regard to surgical site infection and implant removal rate. Concurrent intra-articular injection and plate surface treatment with leukocyte reduced PRP at the time of TPLO, is beneficial in slowing the progression of OA, hastening the radiographic evidence of osteotomy healing, and improved lameness score on recheck examination. Leukocyte reduced PRP was not a significant factor in reducing SSI or implant removal rate.
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Affiliation(s)
- Yazdan Aryazand
- VCA West Los Angeles, Los Angeles, California, United States of America
| | - Nicole J. Buote
- Department of Clinical Sciences, Small Animal Surgery Section, Cornell University College of Veterinary Medicine, Ithaca, New York, United States of America
| | - YuHung Hsieh
- VCA West Los Angeles, Los Angeles, California, United States of America
| | - Kei Hayashi
- Department of Clinical Sciences, Small Animal Surgery Section, Cornell University College of Veterinary Medicine, Ithaca, New York, United States of America
| | - Desiree Rosselli
- VCA West Los Angeles, Los Angeles, California, United States of America
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12
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Pezzanite LM, Chow L, Griffenhagen GM, Bass L, Goodrich LR, Impastato R, Dow S. Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system. Front Vet Sci 2023; 10:1109473. [PMID: 36876001 PMCID: PMC9978772 DOI: 10.3389/fvets.2023.1109473] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 01/26/2023] [Indexed: 02/18/2023] Open
Abstract
Introduction Multiple biological therapies for orthopedic injuries are marketed to veterinarians, despite a lack of rigorous comparative biological activity data to guide informed decisions in selecting a most effective compound. Therefore, the goal of this study was to use relevant bioassay systems to directly compare the anti-inflammatory and immunomodulatory activity of three commonly used orthobiological therapies (OTs): mesenchymal stromal cells (MSC), autologous conditioned serum (ACS), and platelet rich plasma (PRP). Methods Equine monocyte-derived macrophages were used as the readout system to compare therapies, including cytokine production and transcriptomic responses. Macrophages were stimulated with IL-1ß and treated 24 h with OTs, washed and cultured an additional 24 h to generate supernatants. Secreted cytokines were measured by multiplex immunoassay and ELISA. To assess global transcriptomic responses to treatments, RNA was extracted from macrophages and subjected to full RNA sequencing, using an Illumina-based platform. Data analysis included comparison of differentially expressed genes and pathway analysis in treated vs. untreated macrophages. Results All treatments reduced production of IL-1ß by macrophages. Secretion of IL-10 was highest in MSC-CM treated macrophages, while PRP lysate and ACS resulted in greater downregulation of IL-6 and IP-10. Transcriptomic analysis revealed that ACS triggered multiple inflammatory response pathways in macrophages based on GSEA, while MSC generated significant downregulation of inflammatory pathways, and PRP lysate induced a mixed immune response profile. Key downregulated genes in MSC-treated cultures included type 1 and type 2 interferon response, TNF-α and IL-6. PRP lysate cultures demonstrated downregulation of inflammation-related genes IL-1RA, SLAMF9, ENSECAG00000022247 but concurrent upregulation of TNF-α, IL-2 signaling, and Myc targets. ACS induced upregulation of inflammatory IL-2 signaling, TNFα and KRAS signaling and hypoxia, but downregulation of MTOR signaling and type 1 interferon signaling. Discussion These findings, representing the first comprehensive look at immune response pathways for popular equine OTs, reveal distinct differences between therapies. These studies address a critical gap in our understanding of the relative immunomodulatory properties of regenerative therapies commonly used in equine practice to treat musculoskeletal disease and will serve as a platform from which further in vivo comparisons may build.
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Affiliation(s)
- Lynn M. Pezzanite
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Lyndah Chow
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Gregg M. Griffenhagen
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Luke Bass
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Laurie R. Goodrich
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Renata Impastato
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Steven Dow
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
- Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
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13
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Alves JC, Santos A, Jorge P, Carreira LM. A Comparison of Intra-Articular Blood Cell Secretome and Blood Cell Secretome with Triamcinolone Acetonide in Dogs with Osteoarthritis: A Crossover Study. Animals (Basel) 2022; 12:3358. [PMID: 36496879 PMCID: PMC9741238 DOI: 10.3390/ani12233358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/23/2022] [Accepted: 11/28/2022] [Indexed: 12/03/2022] Open
Abstract
Osteoarthritis (OA) is a growing welfare problem for dogs and a challenge to manage for the clinician, and most therapeutic options aim to control pain. In a randomized, double-blinded, placebo-controlled, 2-way, 2-period crossover study, we aimed to evaluate the use of Blood Cell Secretome (BCS) administrated intra-articularly, with or without the combination with triamcinolone, in dogs with bilateral hip OA. BCS is an acellular orthobiologic containing anti-inflammatory and anabolic proteins produced from the patient’s own blood through extended coagulation in a defined environment. Fifteen dogs were initially assigned to a BCS group (BCSG, n = 5), a triamcinolone group (TG, n = 5), or a combination group (BCS+TG, n = 5). All had bilateral hip OA. After a 180-day follow-up, the crossover was performed with BCSG (n = 7) and BCS+TG (n = 7). BCSG received a single intra-articular administration of 3 mL of Blood Cell Secretome, and BCS+TG received BCS plus 0.5 mL of triamcinolone acetonide (40 mg/mL). The volume in BCSG was corrected to 3.5 mL with saline. In all patients, both hips were treated. For treatment follow-up, a copy of the Canine Brief Pain Inventory (divided into pain interference score—PIS and Pain Severity Score—PSS), Liverpool Osteoarthritis in Dogs (LOAD), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) was completed on days 0, 8, 15, 30, 60, 90, 120, 150, and 180. Results were analyzed with the Mann−Whitney U test, effect size, and Kaplan−Meier estimators, followed by the log-rank test. p was set at <0.05. Patients of the sample had a mean age of 9.6 ± 2.9 years and a body weight of 29.2 ± 3.9 kg. Seven hips were classified as severe osteoarthritis, and eight were classified as moderate. No differences were found between groups at T0. Significant differences were observed in PSS scores at +8d, with BCS+TG exhibiting better results. PIS, PSS, LOAD, stiffness, and function scores were also lower in BCS+TG from +15 to +60d. The two groups showed similar improvements from +90 to +120d. Kaplan−Meier estimators showed that dogs in BCS+TG showed clinically-important differences for longer, despite a positive result in BCSG. The intra-articular administration of BCS alone was able to improve the overall condition of OA patients. Its combined use with triamcinolone acetonide lead to a faster and longer-lasting improvement in pain scores.
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Affiliation(s)
- J. C. Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal
- MED—Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554 Évora, Portugal
| | - Ana Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal
| | - Patrícia Jorge
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal
| | - L. Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), 1300-477 Lisbon, Portugal
- Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV/ULisboa), 1649-004 Lisboa, Portugal
- Anjos of Assis Veterinary Medicine Centre (CMVAA), 2830-077 Barreiro, Portugal
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14
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Effect of Leukoreduced Platelet Rich Plasma on Intra-Articular Pro-Inflammatory Cytokines in a Canine Pilot Study. Animals (Basel) 2022; 12:ani12172163. [PMID: 36077884 PMCID: PMC9454790 DOI: 10.3390/ani12172163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/09/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary This study provides initial information on the effect of platelet rich plasma in some of the most important pro-inflammatory cytokines identified in osteoarthritic stifle joint in dogs. The use of platelet rich plasma is getting more popular in the veterinary field but its effect in those cytokines is not known. Abstract Evaluation of effect of Leukoreduced Platelet Rich Plasma (LrPRP) on TNF-α and IL-6 (pro-inflammatory cytokines) in joint fluid in dogs with cranial cruciate ligament rupture (CCLR). Eight client-owned dogs with CCLR were assigned to treatment (2 mL LrPRP) or control (2 mL saline) injection groups. Day of evaluation (day 0) and day of surgery (day 10–14), joint fluid was collected and joint injected. Joint fluid was also collected on day of suture removal (day 20–28). TNF-α and IL-6 concentrations of joint fluid were measured using a bead-based antibody assay. Concentrations at the later time points were expressed as a ratio to the initial level within each stifle. LrPRP had a mean concentration of platelets 1.7 times higher that of whole blood on day of evaluation and 1.4 times higher on day of the surgery. Leukocytes were reduced by 99.7%. On day of surgery, TNF-α ratios in the joint fluid from dogs injected with LrPRP were significantly different that TNF-α ratios of control group. On the day of suture removal ratios of IL-6 and TNF-α were lower in LrPRP treatment group compared with control group; however, differences were not significant. LrPRP modulate ratios of pro-inflammatory cytokine TNF-α in dogs with CCLR.
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15
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Alves JC, Santos A, Jorge P, Carreira LM. A first report on the efficacy of a single intra-articular administration of blood cell secretome, triamcinolone acetonide, and the combination of both in dogs with osteoarthritis. BMC Vet Res 2022; 18:309. [PMID: 35962448 PMCID: PMC9375423 DOI: 10.1186/s12917-022-03413-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 08/08/2022] [Indexed: 11/17/2022] Open
Abstract
Background Osteoarthritis represents a significant welfare problem for many dogs, with limited therapeutic options other than palliative pain control. To evaluate the effect of the intra-articular administration of blood cell secretome and triamcinolone, 15 dogs with bilateral hip osteoarthritis were randomly assigned to a blood cell secretome (BCSG, n = 5), triamcinolone (TG) or their combination group (BCS + TG, n = 5). BCSG received a single intra-articular administration of 3 ml of blood cell secretome, TG 0.5 ml of triamcinolone acetonide 40 mg/ml, and BCS + TG received the combined products. The volume to administrate was corrected to 3.5 ml with saline. On days 0, 8, 15, 30, 60, 90, 120, 150, and 180, a copy of the Canine Brief Pain Inventory (divided into pain interference score—PIS and Pain Severity Score—PSS), Liverpool Osteoarthritis in Dogs (LOAD), Hudson Visual Analogue Scale (HVAS), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) was completed. Results were analyzed with the Kruskal–Wallis test and the Kaplan–Meier estimators were conducted and compared with the Log Rank test, p < 0.05. Results Animals in the sample had a mean age of 9.0 ± 2.9 years and a bodyweight of 28.8 ± 4.1 kg. Hips were classified as moderate (8) and severe (7) osteoarthritis. No differences were found between groups at T0 regarding considered evaluations. Significant differences were observed between groups in pain scores from + 8d- + 150d, with BCS + TG exhibiting better results. The same was observed for HVAS and LOAD, from + 8d- + 120d. Improvements were also observed in several dimensions of the COI. Kaplan–Meier estimators showed that BCS + TG produced longer periods with better results, followed by BCSG and TG. Conclusion The intra-articular administration of blood cell secretome improved the clinical signs and scores of several clinical metrology instruments in dogs with hip OA, particularly when combined with triamcinolone. Further studies are required.
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Affiliation(s)
- J C Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal. .,Environment and Development, MED - Mediterranean Institute for Agriculture, Instituto de Investigação E Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554, Évora, Portugal.
| | - A Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal
| | - P Jorge
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal
| | - L Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), Lisbon, Portugal.,Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon, (FMV/ULisboa), Lisbon, Portugal.,Anjos of Assis Veterinary Medicine Centre (CMVAA), Barreiro, Portugal
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16
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Mosley C, Edwards T, Romano L, Truchetti G, Dunbar L, Schiller T, Gibson T, Bruce C, Troncy E. Proposed Canadian Consensus Guidelines on Osteoarthritis Treatment Based on OA-COAST Stages 1–4. Front Vet Sci 2022; 9:830098. [PMID: 35558892 PMCID: PMC9088681 DOI: 10.3389/fvets.2022.830098] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 03/21/2022] [Indexed: 11/13/2022] Open
Abstract
The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1–4.
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Affiliation(s)
- Conny Mosley
- Elanco Animal Health, Mississauga, ON, Canada
- VCA Canada, 404 Veterinary Emergency and Referral Hospital, Newmarket, ON, Canada
- *Correspondence: Conny Mosley
| | - Tara Edwards
- VCA Canada, Central Victoria Veterinary Hospital, Victoria, BC, Canada
| | - Laura Romano
- VCA Canada, Centra Victoria Veterinary Hospital, Victoria, BC, Canada
| | | | | | - Teresa Schiller
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
| | - Tom Gibson
- Grand River Veterinary Surgical Services; Adjunct Faculty OVC, Mississauga, ON, Canada
| | - Charles Bruce
- Pulse Veterinary Specialists and Emergency, Sherwood Park, AB, Canada
| | - Eric Troncy
- Faculté de médecine vétérinaire, Université de Montréal, Groupe de recherche en pharmacologie animale du Québec (GREPAQ), Montreal, QC, Canada
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DeMello V, Chen G, Wakshlag J, Mason D. Evaluation of Platelet and Leukocyte Counts in Canine Platelet-Rich Plasma Obtained After Successive Blood Collections From the Same Patient and the Effects of Freezing on the Concentration of Growth Factors Present in It. Front Vet Sci 2022; 9:838481. [PMID: 35464390 PMCID: PMC9020877 DOI: 10.3389/fvets.2022.838481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/28/2022] [Indexed: 11/24/2022] Open
Abstract
Objective The purpose of this study was 2-fold: to evaluate whether the timing of collection influences the platelet counts and leukocyte counts of PRP samples, and to evaluate growth factor concentrations in canine PRP after freezing and storage without a preservation agent for 6 months of time. Materials and Methods Whole blood collection was performed three times over the course of 4 weeks. All PRP samples were evaluated with a CBC analysis. The PRP samples were frozen and stored without a preservation agent for the duration of the 4-week study. Results The platelet and leukocyte counts were not statistically significant between the timing of blood draws over the course of 4 weeks. All three growth factors were present in measurable quantities after freezing and storage for 6 months without a preservation agent. Clinical Relevance PDGF, TGF-β1, and VEGF were all present in measurable quantities. Furthermore, PDGF and TGF-β1 were correlated with platelet count of the final PRP. VEGF concentrations were able to be quantified. We correctly hypothesized growth factor concentrations would be present and measurable in canine PRP frozen and stored without a preservation agent for 6 months.
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Affiliation(s)
- Victoria DeMello
- LasVegas Veterinary Specialty Center, Las Vegas, NV, United States
| | - Grace Chen
- LasVegas Veterinary Specialty Center, Las Vegas, NV, United States
| | - Joseph Wakshlag
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, United States
| | - David Mason
- LasVegas Veterinary Specialty Center, Las Vegas, NV, United States
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Platelet Lysate for Mesenchymal Stromal Cell Culture in the Canine and Equine Species: Analogous but Not the Same. Animals (Basel) 2022; 12:ani12020189. [PMID: 35049811 PMCID: PMC8773277 DOI: 10.3390/ani12020189] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Regenerative medicine using platelet-based blood products or adult stem cells offers the prospect of better clinical outcomes with many diseases. In veterinary medicine, most progress has been made with the development and therapeutic use of these regenerative therapeutics in horses, but the clinical need is given in dogs as well. Our aim was to transfer previous advances in the development of horse regenerative therapeutics, specifically the use of platelet lysate for feeding stem cell cultures, to the dog. Here, we describe the scalable production of canine platelet lysate, which could be used in regenerative biological therapies. We also evaluated the canine platelet lysate for its suitability in feeding canine stem cell cultures in comparison to equine platelet lysate used for equine stem cell cultures. Platelet lysate production from canine blood was successful, but the platelet lysate did not support stem cell culture in dogs in the same beneficial way observed with the equine platelet lysate and stem cells. In conclusion, canine platelet lysate can be produced in large scales as described here, but further research is needed to improve the cultivation of canine stem cells. Abstract Platelet lysate (PL) is an attractive platelet-based therapeutic tool and has shown promise as xeno-free replacement for fetal bovine serum (FBS) in human and equine mesenchymal stromal cell (MSC) culture. Here, we established a scalable buffy-coat-based protocol for canine PL (cPL) production (n = 12). The cPL was tested in canine adipose MSC (n = 5) culture compared to FBS. For further comparison, equine adipose MSC (n = 5) were cultured with analogous equine PL (ePL) or FBS. During canine blood processing, platelet and transforming growth factor-β1 concentrations increased (p < 0.05 and p < 0.001), while white blood cell concentrations decreased (p < 0.05). However, while equine MSC showed good results when cultured with 10% ePL, canine MSC cultured with 2.5% or 10% cPL changed their morphology and showed decreased metabolic activity (p < 0.05). Apoptosis and necrosis in canine MSC were increased with 2.5% cPL (p < 0.05). Surprisingly, passage 5 canine MSC showed less genetic aberrations after culture with 10% cPL than with FBS. Our data reveal that using analogous canine and equine biologicals does not entail the same results. The buffy-coat-based cPL was not adequate for canine MSC culture, but may still be useful for therapeutic applications.
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Platelet-rich plasma injections induce disease-modifying effects in the treatment of osteoarthritis in animal models. Knee Surg Sports Traumatol Arthrosc 2021; 29:4100-4121. [PMID: 34341845 DOI: 10.1007/s00167-021-06659-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/01/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE The mechanisms of action and disease-modifying potential of platelet-rich plasma (PRP) injection for osteoarthritis (OA) treatment are still not fully established. The aim of this systematic review of preclinical evidence was to determine if PRP injections can induce disease-modifying effects in OA joints. METHODS A systematic review was performed on animal studies evaluating intra-articular PRP injections as treatment for OA joints. A synthesis of the results was performed investigating the disease-modifying effects of PRP by evaluating studies that compared PRP with OA controls or other injectable products, different PRP formulations or injection intervals, and the combination of PRP with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS Forty-four articles were included, for a total of 1251 animals. The publication trend remarkably increased over time. PRP injections showed clinical effects in 80% and disease-modifying effects in 68% of the studies, attenuating cartilage damage progression and reducing synovial inflammation, coupled with changes in biomarker levels. Evidence is limited on the best PRP formulation, injection intervals, and synergistic effect with other injectables. The risk of bias was low in 40%, unclear in 56%, and high in 4% of items. CONCLUSION Intra-articular PRP injections showed disease-modifying effects in most studies, both at the cartilage and synovial level. These findings in animal OA models can play a crucial role in understanding mechanism of action and structural effects of this biological approach. Nevertheless, the overall low quality of the published studies warrants further preclinical studies to confirm the positive findings, as well as high-level human trials to demonstrate if these results translate into disease-modifying effects when PRP is used in the clinical practice to treat OA. LEVEL OF EVIDENCE Level II.
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20
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Attili AR, Iacoucci C, Serri E, Cuteri V, Cantalamessa A, Linardi M, Rifici C, Mazzullo G, Rossi G, Galosi L, Tambella AM. Antibacterial Properties of Canine Platelet-Rich Plasma and Other Non-Transfusional Hemo-Components: An in vitro Study. Front Vet Sci 2021; 8:746809. [PMID: 34671662 PMCID: PMC8520915 DOI: 10.3389/fvets.2021.746809] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 08/26/2021] [Indexed: 01/13/2023] Open
Abstract
This in vitro study was carried out to evaluate the potential antibacterial properties of canine non-transfusional hemo-components. Therapeutic formulations commonly used for regenerative medicine purposes (platelet-rich plasma, platelet gel, platelet lysate, fibrin glue), considering both leukocyte-rich and leukocyte-poor formulations, but also platelet-poor plasma and activating substances (thrombin, calcium gluconate), were tested to detect elements with potential antimicrobial properties. The antibacterial effect was tested on different bacterial strains (Staphylococcus aureus subspecies aureus, Staphylococcus cohnii subspecies cohnii, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae subspecies pneumoniae) isolated from canine wounds and classified as susceptible, multidrug-, extensively, and pandrug-resistant bacteria toward a known panel of human and veterinary antibiotics. The evaluation was carried out by agar gel diffusion method (Kirby-Bauer) and micro-inhibition in broth using microplates and spectrophotometer reading. The study findings confirmed the hypothesized antibacterial properties of canine non-transfusional hemo-components. A more effective bacteriostatic effect was found against Gram-negative bacteria, drug-resistant too. The presence of leukocytes or platelets does not appear to be essential for the antibacterial effect. Further studies should be conducted to evaluate the exact mechanism of action of the antimicrobial activity. However, non-transfusional hemo-components could be a useful natural aid in controlling bacterial infections in dogs.
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Affiliation(s)
- Anna-Rita Attili
- Laboratory of Medical Microbiology and Infectious Diseases, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Cristina Iacoucci
- Laboratory of Medical Microbiology and Infectious Diseases, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Evelina Serri
- Veterinary Teaching Hospital, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Vincenzo Cuteri
- Laboratory of Medical Microbiology and Infectious Diseases, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Andrea Cantalamessa
- Laboratory of Medical Microbiology and Infectious Diseases, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Martina Linardi
- Laboratory of Medical Microbiology and Infectious Diseases, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Claudia Rifici
- Pathology Laboratory, Department of Veterinary Sciences, University of Messina, Messina, Italy
| | - Giuseppe Mazzullo
- Pathology Laboratory, Department of Veterinary Sciences, University of Messina, Messina, Italy
| | - Giacomo Rossi
- Pathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Livio Galosi
- Pathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Adolfo Maria Tambella
- Veterinary Teaching Hospital, School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
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21
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Sanghani-Kerai A, Black C, Cheng SO, Collins L, Schneider N, Blunn G, Watson F, Fitzpatrick N. Clinical outcomes following intra-articular injection of autologous adipose-derived mesenchymal stem cells for the treatment of osteoarthritis in dogs characterized by weight-bearing asymmetry. Bone Joint Res 2021; 10:650-658. [PMID: 34628940 PMCID: PMC8559970 DOI: 10.1302/2046-3758.1010.bjr-2020-0540.r1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
AIMS This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. METHODS With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. RESULTS AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). CONCLUSION These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650-658.
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Affiliation(s)
| | | | | | | | | | - G Blunn
- School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
| | - Fraje Watson
- Fitzpatrick Referrals, Godalming, UK.,Institute of Orthopaedic & Musculoskeletal Science, University College London, London, UK
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22
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Hayashi K, Bourgeois A, Lopez D, Caserto BG, Berthelsen E, Krotscheck U, Reesink HL, Kim SY, Putnam D. Intra-Articular Administration of a Synthetic Lubricin in Canine Stifles. Vet Comp Orthop Traumatol 2021; 35:90-95. [PMID: 34598303 DOI: 10.1055/s-0041-1736189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate the functional, systemic, synovial and articular changes after intra-articular administration of a synthetic lubricin within healthy canine stifles. STUDY DESIGN A prospective randomized blinded placebo-controlled study composed of 10 dogs equally divided into either a treatment group (intra-articular synthetic lubricin injection, n = 5) or control group (saline, n = 5). Clinical (orthopaedic examination, gait observation, gait analysis), biochemical (complete blood count and biochemistry profile) and local tissue outcomes (joint fluid analysis, joint capsule and articular cartilage histopathology) were evaluated over a time period of 3 months. RESULTS No significant differences between the treatment group and control group were identified with regard to baseline patient parameters. No clinically significant orthopaedic examination abnormalities, gait abnormalities, biochemical alterations, joint fluid alterations or histopathological alterations were identified over the course of the study. CONCLUSION The synthetic lubricin studied herein is both biocompatible and safe for a single administration within the canine stifle joint. Further research is necessary to evaluate the clinical efficacy of the synthetic lubricin in canine osteoarthritic joints.
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Affiliation(s)
- Kei Hayashi
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
| | - Alexandria Bourgeois
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
| | - Daniel Lopez
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
| | | | - Erin Berthelsen
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
| | - Ursula Krotscheck
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
| | - Heidi L Reesink
- College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
| | - Sun Young Kim
- Purdue University College of Veterinary Medicine, West Lafayette, Indiana, United States
| | - David Putnam
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, United States.,Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, United States
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23
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Platelet-rich plasma therapy in dogs with bilateral hip osteoarthritis. BMC Vet Res 2021; 17:207. [PMID: 34090433 PMCID: PMC8180029 DOI: 10.1186/s12917-021-02913-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 05/19/2021] [Indexed: 01/08/2023] Open
Abstract
Background Osteoarthritis (OA) is the most commonly diagnosed joint disease in companion animals, and hip OA is commonly diagnosed in the canine population. The use of platelet-rich plasma has gained increasing interest for the treatment of musculoskeletal conditions in companion animals. To evaluate the effect of the intra-articular administration of platelet-rich plasma in police working dogs with bilateral hip OA compared to a control group, twenty dogs were assigned to a control group (CG, n = 10) or treatment group (PG, n = 10), using the statistical analysis software. PG received two intra-articular administrations of platelet-rich plasma, 14 days apart, while CG received an intra-articular administration of saline, in the same moments. Response to treatment was determined with the Canine Brief Pain Inventory, Liverpool Osteoarthritis in Dogs, Canine Orthopedic Index, and Hudson Visual Analogue Scale, before treatment, + 8, + 15, + 30, + 60, + 90, + 120, 150, and + 180 days after initial treatment. Kaplan-Meier estimators were conducted and compared with the log-rank test. Cox proportional hazard regression analysis was performed to determine treatment survival, p < 0.05. Results The sample comprised 20 animals of both sexes (male n = 12, female n = 8), with a mean age of 8.4 ± 2.4 years and a bodyweight of 31.5 ± 5.7 kg. Joints were classified as moderate (13) and severe (7) according to the Orthopedic Foundation for Animals grading scheme. No differences were found between groups at the initial evaluation. Better results with the majority of scores were observed in the PG, in some cases lasting up to the last evaluation moment. Kaplan-Meier estimators showed that PG produced longer periods with better results in all scores compared to CG. Treatment was the covariate influencing all scores in the Cox regression analysis. OFA hip score also influenced two dimensions of the Canine Orthopedic Index. Conclusion The intra-articular administration of platelet-rich plasma can improve pain and functional scores of police working dogs with bilateral hip OA, compared with a control group. Its effects lasted for significantly longer periods, and treatment was the main covariate affecting the improvements observed.
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24
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Woodell-May J, Steckbeck K, King W. Potential Mechanism of Action of Current Point-of-Care Autologous Therapy Treatments for Osteoarthritis of the Knee-A Narrative Review. Int J Mol Sci 2021; 22:ijms22052726. [PMID: 33800401 PMCID: PMC7962845 DOI: 10.3390/ijms22052726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/21/2021] [Accepted: 02/23/2021] [Indexed: 12/13/2022] Open
Abstract
Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.
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Affiliation(s)
| | | | - William King
- Owl Manor, 720 East Winona Avenue, Warsaw, IN 46580, USA;
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25
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Alves JCA, Santos AMMPD, Jorge PIF, Lavrador CFTVB, Carreira LMA. Management of Osteoarthritis Using 1 Intra-articular Platelet Concentrate Administration in a Canine Osteoarthritis Model. Am J Sports Med 2021; 49:599-608. [PMID: 33428459 DOI: 10.1177/0363546520981558] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Osteoarthritis (OA) represents a significant burden to societies, as it affects quality of life and performance and implies a large cost in terms of health care. Autologous platelets are a regenerative treatment modality for OA that are thought to be a potential stimulation of the natural healing cascade. PURPOSE To describe the effect of the platelet concentrate V-PET in the management of OA in a naturally occurring canine model, using several outcome assessment modalities. STUDY DESIGN Controlled laboratory study. METHODS A total of 40 joints of active working police dogs with hip OA were randomly assigned to a control group (CG) and a platelet concentrate group (PCG; treatment) and evaluated. At treatment day (T0) and 8, 15, 30, 90, and 180 days after treatment, weight distribution, joint range of motion at flexion and extension, thigh girth, digital thermography, radiographic signs, 4 clinical metrology instruments, and synovial fluid interleukin 1 and C-reactive protein levels were recorded. Results were compared using repeated-measures analysis of variance with a Huynh-Feldt correction, paired-samples t test, or Wilcoxon signed rank test, with P < .05. RESULTS Dogs were 6.5 ± 2.4 years old (mean ± SD) and had a body weight of 26.7 ± 5.2 kg. At T0, 32 (80%) joints were graded as having mild OA, 6 (15%) as moderate, and 2 (5%) as severe. No differences were found between groups at T0. Between the PCG and CG, the symmetry index showed significant improvements in the PCG from 8 days (P = .01) to 180 days (P = .01). Joint flexion also improved in the PCG up to 90 days (P < .05) and extension improved up to 180 days (P < .01). Several clinical metrology instrument scores also improved up to 90 to 180 days after treatment. In the CG, radiographic signs progressed, while the PCG showed some improved signs. In both groups, increasing body weight and age corresponded with worse clinical and laboratory findings. CONCLUSION A single injection of platelet concentrate had a positive effect, lasting up to 6 months, on several clinical, imaging, and laboratory signs in a naturally occurring canine OA model. CLINICAL RELEVANCE We characterized the effects of this platelet concentrate in dogs, considered the gold standard of the study of OA, with a group of working animals with similar high demands as athletes.
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Affiliation(s)
- João Carlos Agostinho Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana, Lisbon, Portugal.,Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Évora, Portugal
| | | | | | | | - Luis Miguel Alves Carreira
- Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.,Interdisciplinary Centre for Research in Animal Health, University of Lisbon, Lisbon, Portugal.,Anjos of Assis Veterinary Medicine Centre, Barreiro, Portugal
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26
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Alves JC, Santos A, Jorge P, Lavrador C, Carreira LM. Intraarticular triamcinolone hexacetonide, stanozolol, Hylan G-F 20 and platelet concentrate in a naturally occurring canine osteoarthritis model. Sci Rep 2021; 11:3118. [PMID: 33542412 PMCID: PMC7862601 DOI: 10.1038/s41598-021-82795-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 01/25/2021] [Indexed: 01/30/2023] Open
Abstract
Osteoarthritis (OA) is a disease transversal to all mammals, a source of chronic pain and disability, a huge burden to societies, with a significant toll in healthcare cost, while reducing productivity and quality of life. The dog is considered a useful model for the translational study of the disease, closely matching human OA, with the advantage of a faster disease progression while maintaining the same life stages. In a prospective, longitudinal, double-blinded, negative controlled study, one hundred (N = 100) hip joints were selected and randomly assigned to five groups: control group (CG, n = 20, receiving a saline injection), triamcinolone hexacetonide group (THG, n = 20), platelet concentrate group (PCG, n = 20), stanozolol group (SG, n = 20) and hylan G-F 20 group (HG). Evaluations were conducted on days 0 (T0, treatment day), 8, 15, 30, 60, 90, 120, 150 and 180 days post-treatment, consisting of weight distribution analysis and data from four Clinical Metrology Instruments (CMI). Kaplan-Meier estimators were generated and compared with the Breslow test. Cox proportional hazard regression analysis was used to investigate the influence of variables of interest on treatment survival. All results were analyzed with IBM SPSS Statistics version 20 and a significance level of p < 0.05 was set. Sample included joints of 100 pelvic limbs (of patients with a mean age of 6.5 ± 2.4 years and body weight of 26.7 ± 5.2 kg. Joints were graded as mild (n = 70), moderate (n = 20) and severe (n = 10) OA. No differences were found between groups at T0. Kaplan-Meier analysis showed that all treatments produced longer periods with better results in the various evaluations compared to CG. Patients in HG and PCG took longer to return to baseline values and scores. A higher impact on pain interference was observed in THG, with a 95% improvement over CG. PCG and HG experienced 57-81% improvements in functional evaluation and impairments due to OA, and may be a better options for these cases. This study documented the efficacy of several approaches to relieve OA clinical signs. These approaches varied in intensity and duration. HG and PCG where the groups were more significant improvements were observed throughout the follow-up periods, with lower variation in results.
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Affiliation(s)
- J C Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal.
- MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554, Évora, Portugal.
| | - A Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal
| | - P Jorge
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal
| | - C Lavrador
- MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554, Évora, Portugal
| | - L Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), Lisbon, Portugal
- Interdisciplinary Centre for Research in Animal Health (CIISA) - University of Lisbon, (FMV/ULisboa), Lisbon, Portugal
- Anjos of Assis Veterinary Medicine Centre (CMVAA), Barreiro, Portugal
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27
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Alves JC, Santos A, Jorge P, Lavrador C, Carreira LM. Intra-articular Injections With Either Triamcinolone Hexacetonide, Stanozolol, Hylan G-F 20, or a Platelet Concentrate Improve Clinical Signs in Police Working Dogs With Bilateral Hip Osteoarthritis. Front Vet Sci 2021; 7:609889. [PMID: 33537353 PMCID: PMC7849590 DOI: 10.3389/fvets.2020.609889] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/02/2020] [Indexed: 12/13/2022] Open
Abstract
Objectives: To compare the effect of intra-articular treatment with triamcinolone hexacetonide (TH), stanozolol, hyaluronan, and a platelet concentrate in police working dogs with bilateral hip osteoarthritis (OA). Study Design: Prospective, longitudinal, double-blinded, negative controlled study. Sample Population: Fifty police working dogs with naturally occurring hip OA. Methods: Animals were randomly assigned to a control group (CG, n = 10), TH group (THG, n = 10), platelet concentrate group (PCG, n = 10), stanozolol group (SG, n = 10), and Hylan G-F 20 group (HG). On days 0 (T0), 8, 15, 30, 90, and 180 days post-treatment, weight-bearing distribution was evaluated. In those days, and on days 60, 120, and 150, four clinical metrology instruments were completed. Kaplan-Meier estimators were conducted and compared with the log-rank test. Cox proportional hazard regression analysis was performed to determine treatment survival. Significance was set at p < 0.05. Results: Patients had a mean age of 6.5 ± 2.4 years and body weight of 26.7 ± 5.2 kg. At T0, hips were classified as mild (n = 35), moderate (n = 10), and severe (n = 5), according to the Orthopedic Foundation for Animals grading scheme. No differences were found between groups at that moment considering age, body weight, OFA hip score, and all assessments performed. All treatments improved clinical signs in various OA dimensions in some groups, with a broad effect interval. PCG showed a lower range of variation while maintaining a positive result for more extended periods (p < 0.01 for symmetry index and 0.01 < p < 0.04 in the majority of scores). Breed, age, sex, and OFA grade did not significantly influence response to treatment. Conclusions and Clinical Relevance: This is the first prospective, negative controlled, double-blinded study to compare the effect of a single administration of these IA treatments in dogs with hip OA. HG and PCG recorded more significant improvements throughout the 180-day follow-up. In particular, PCG also registered a lower variation in results, seemingly the best therapeutic option. Nevertheless, improvements were still observed in THG and SG, and these treatment options can be considered, mainly when the first two treatments are not available.
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Affiliation(s)
- João C. Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Lisbon, Portugal,MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Forma Avana, Universidade de Évora, Évora, Portugal,*Correspondence: João C. Alves
| | - Ana Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Lisbon, Portugal
| | - Patrícia Jorge
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Lisbon, Portugal
| | - Catarina Lavrador
- MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Forma Avana, Universidade de Évora, Évora, Portugal
| | - L. Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal,Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon, Lisbon, Portugal,Anjos of Assis Veterinary Medicine Centre (CMVAA), Barreiro, Portugal
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28
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Maki CB, Beck A, Wallis CBCC, Choo J, Ramos T, Tong R, Borjesson DL, Izadyar F. 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. Front Vet Sci 2020; 7:570. [PMID: 33110913 PMCID: PMC7489271 DOI: 10.3389/fvets.2020.00570] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/16/2020] [Indexed: 01/07/2023] Open
Abstract
This study was conducted to investigate the therapeutic effect of allogeneic adipose-derived MSCs on dogs with hip osteoarthritis (OA). Twenty dogs with bilateral osteoarthritis of the coxofemoral (hip) joint, diagnosed by a veterinarian through physical examination and radiographs were randomly allocated into four groups. Group 1 served as a placebo control and were injected with 0.9% sodium chloride (saline) (n = 4). Group 2 were injected with a single dose of 5 million MSCs (n = 5). Group 3 received a single dose of 25 million MSCs (n = 6) and Group 4 received a single dose of 50 million MSCs (n = 5). Intra-articular administration of allogeneic MSCs into multiple joints did not result in any serious adverse events. The average lameness score of the dogs in the placebo control group (−0.31) did not show improvement after 90 days of intra-articular saline administration. However, the average lameness score of the all MSC-treated dogs was improved 2.11 grade at this time point (P < 0.001). Overall, sixty five percent (65%) of the dogs that received various doses of MSCs showed improvement in lameness scores 90 days after intra-articular MSC administration. Our results showed that intra-articular administration of allogeneic adipose derived MSCs was well-tolerated and improved lameness scores and reduced pain in dogs associated with hip OA. All doses of MSCs were effective. Subsequent studies with more animals per group are needed to make a conclusion about the dose response. The improved lameness effect was present up to 90 days post-injection. Serum interleukin 10 was increased in a majority of the dogs that received MSCs and that also had improved lameness.
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Affiliation(s)
- Chad B Maki
- VetCell Therapeutics USA, Santa Ana, CA, United States
| | - Anthony Beck
- Doctors Beck and Stone Clinic, Discovery Bay, Hong Kong
| | | | - Justin Choo
- Doctors Beck and Stone Clinic, Discovery Bay, Hong Kong
| | - Thomas Ramos
- VetCell Therapeutics USA, Santa Ana, CA, United States
| | | | - Dori L Borjesson
- Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, Veterinary Institute for Regenerative Cures, University of California, Davis, Davis, CA, United States
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29
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Soares CS, Babo PS, Reis RL, Carvalho PP, Gomes ME. Platelet-Derived Products in Veterinary Medicine: A New Trend or an Effective Therapy? Trends Biotechnol 2020; 39:225-243. [PMID: 32868100 DOI: 10.1016/j.tibtech.2020.07.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 12/20/2022]
Abstract
Platelet-derived products (PDPs) have gained popularity, mainly due to their high concentrations of bioactive molecules such as growth factors and cytokines, which play important roles in tissue healing and regeneration. PDPs are obtained through minimally invasive procedures and their therapeutic effect has been widely recognized. In veterinary medicine, however, the lack of standard protocols to generate PDPs is a major hurdle for assessing the clinical relevance of PDP-based therapies and for their widespread usage. The aim of this review is to analyze the technical and scientific specificities of PDPs in terms of preparation methodologies, classification categorization, nomenclature, and biological proprieties to advance their future biotechnological potential in veterinary contexts.
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Affiliation(s)
- Carla S Soares
- 3Bs Research Group, I3Bs, Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Guimarães, Portugal; ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Pedro S Babo
- 3Bs Research Group, I3Bs, Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Guimarães, Portugal; ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L Reis
- 3Bs Research Group, I3Bs, Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Guimarães, Portugal; ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Pedro P Carvalho
- Vasco da Gama Research Center, CIVG, University School Vasco da Gama, Lordemão, 3020-210 Coimbra, Portugal; Vetherapy, Research and Development in Biotechnology, Coimbra, Portugal.
| | - Manuela E Gomes
- 3Bs Research Group, I3Bs, Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Barco, Guimarães, Portugal; ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimarães, Portugal
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30
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Brioschi FA, Di Cesare F, Gioeni D, Rabbogliatti V, Ferrari F, D’Urso ES, Amari M, Ravasio G. Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis. Animals (Basel) 2020; 10:ani10091505. [PMID: 32858828 PMCID: PMC7552307 DOI: 10.3390/ani10091505] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/19/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Osteoarthritis is a progressive and degenerative condition that affects dog populations, causing pain. The pain associated with osteoarthritis is considered to be chronic, owing to both active inflammation and to a maladaptive component caused by central sensitization. Chronic pain in dogs is being increasingly recognised as a significant problem, and finding successful treatments against canine osteoarthritis-related pain is challenging. The aim of this study was to assess the efficacy in pain management over a twelve-week period of oral transmucosal cannabidiol, in combination with a multimodal pharmacological protocol, in dogs affected by spontaneous osteoarthritis. Dogs receiving oral transmucosal cannabidiol in addition to an anti-inflammatory drug, gabapentin and amitriptyline showed a meaningful improvement in Canine Brief Pain Inventory scores, in comparison with dogs that did not receive cannabidiol. The present study suggests that the addition of oral transmucosal cannabidiol to a multimodal pharmacological treatment for canine osteoarthritis improves owner reported pain scores and quality of life of dogs, without severe adverse effects. Abstract The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs. Twenty-one dogs were randomly divided into two groups: in group CBD (n = 9), OTM CBD (2 mg kg−1 every 12 h) was included in the therapeutic protocol (anti-inflammatory drug, gabapentin, amitriptyline), while in group C (n = 12), CBD was not administered. Dogs were evaluated by owners based on the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter. Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.
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Affiliation(s)
| | - Federica Di Cesare
- Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, 20122 Milan, Italy;
| | - Daniela Gioeni
- Department of Veterinary Medicine, Università degli Studi di Milano, 20122 Milan, Italy; (F.A.B.); (D.G.)
| | - Vanessa Rabbogliatti
- Department of Veterinary Medicine, Centro Clinico Veterinario e Zootecnico Sperimentale, Università degli Studi di Milano, 20122 Milan, Italy; (V.R.); (F.F.); (M.A.)
| | - Francesco Ferrari
- Department of Veterinary Medicine, Centro Clinico Veterinario e Zootecnico Sperimentale, Università degli Studi di Milano, 20122 Milan, Italy; (V.R.); (F.F.); (M.A.)
| | | | - Martina Amari
- Department of Veterinary Medicine, Centro Clinico Veterinario e Zootecnico Sperimentale, Università degli Studi di Milano, 20122 Milan, Italy; (V.R.); (F.F.); (M.A.)
| | - Giuliano Ravasio
- Department of Veterinary Medicine, Università degli Studi di Milano, 20122 Milan, Italy; (F.A.B.); (D.G.)
- Correspondence:
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Perego R, Spada E, Baggiani L, Martino PA, Proverbio D. Efficacy of a Semi Automated Commercial Closed System for Autologous Leukocyte- and Platelet-Rich Plasma (l-prp) Production in Dogs: A Preliminary Study. Animals (Basel) 2020; 10:ani10081342. [PMID: 32759643 PMCID: PMC7459512 DOI: 10.3390/ani10081342] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/30/2020] [Accepted: 08/01/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To characterize the cellular composition (platelets, erythrocytes, and leukocytes) and determine platelet-derived growth factor isoform BB (PDGF-BB) concentration in canine leukocyte- and platelet rich plasma (L-PRP) produced using a commercial semi-automated closed system. METHODS Twenty milliliters of citrated whole blood were obtained from 30 healthy un-sedated canine blood donors and processed using a semi-automated completely closed commercial system (CPUNT 20, Eltek group, Casale Monferrato, Alessandria, Italy) according to the manufacturer's instructions. Erythrocyte, leukocyte, and platelet counts were determined in both whole blood (WB) and resultant L-PRP. The PDGF-BB concentration was evaluated after bovine thrombin activation of 10 L-PRP samples. RESULTS This commercial system produced on average 2.3 ± 0.7 mL of L-PRP containing a high concentration of platelets (767,633 ± 291,001 μL, p < 0.001), with a 4.4 fold increase in platelet count, lower concentration of erythrocytes (528,600 ± 222,773 μL, p < 0.001) and similar concentration of leukocytes (8422 ± 6346 μL, p = 0.9918) compared with WB. L-PRP had an average of 3442 ± 2061 pg/mL of PDGF-BB after thrombin activation. Neutrophils, lymphocytes and monocytes average percent content in L-PRP was 14.8 ± 13.2, 71.7 ± 18.5 and 10.7 ± 6.4, respectively. CONCLUSION Sterile canine L-PRP prepared using this semi-automated closed system is easy to obtain, produces a significant increase in platelet count compared to WB and contains a detectable concentration of PDGF-BB after activation. Additional in vitro and in vivo studies are needed to assess inflammatory markers concentration and the therapeutic efficacy of this L-PRP in dogs.
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Affiliation(s)
- Roberta Perego
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
- Correspondence: (R.P.); (E.S.); Tel.: +39-0250334521 (R.P.); +39-0250334520 (E.S.)
| | - Eva Spada
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
- Correspondence: (R.P.); (E.S.); Tel.: +39-0250334521 (R.P.); +39-0250334520 (E.S.)
| | - Luciana Baggiani
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
| | - Piera Anna Martino
- Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy;
| | - Daniela Proverbio
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
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Ferrari JT, Schwartz P. Prospective Evaluation of Feline Sourced Platelet-Rich Plasma Using Centrifuge-Based Systems. Front Vet Sci 2020; 7:322. [PMID: 32596269 PMCID: PMC7303265 DOI: 10.3389/fvets.2020.00322] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 05/11/2020] [Indexed: 12/30/2022] Open
Abstract
Objective: To evaluate the hematologic components of platelet-rich plasma (PRP) generated using feline blood with two commercially available centrifuge-based systems1,2. Materials and methods: Twenty healthy adult cats were enrolled in this prospective study from November 2018 to January 2019. Feline blood samples were obtained for analysis of whole blood (WB) cellular components and preparation of PRP product. PRP was prepared using two commercial systems and complete blood count (CBC) testing was performed on both WB and PRP samples. The cellular composition of the PRP product was compared to the WB sample for each patient. Results: Both systems showed significant decrease of median RBC concentration in PRP products compared to WB samples (P = 0.002 for both systems). System 1 significantly decreased median WBC concentration (P = 0.002). System 2 decreased WBC concentration, though statistical significance was not reached (P = 0.63). Median platelet concentration was decreased by 3% using System 1, and increased by 187% using System 2. Platelet aggregation presented a challenge with 8/20 (40%) of samples demonstrating platelet aggregation. Clinical relevance: Commercial systems available for generation of PRP may be useful for creating a feline sourced product and in this study showed promise in decreasing RBC and WBC concentration. Neither system tested achieved 2–5 times platelet concentration from baseline. Platelet aggregation presented a significant obstacle to reliable generation of PRP products using feline blood. This treatment modality may be particularly beneficial for feline patients with osteoarthritis and soft tissue injuries, though first characterizing the PRP product made using feline blood is critical to validate its use in further clinical studies.
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Affiliation(s)
- Jonathan T Ferrari
- Department of Surgery, The Animal Medical Center, New York, NY, United States
| | - Pamela Schwartz
- Department of Surgery, The Animal Medical Center, New York, NY, United States
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Venator KP, Frye CW, Gamble LJ, Wakshlag JJ. Assessment of a Single Intra-Articular Stifle Injection of Pure Platelet Rich Plasma on Symmetry Indices in Dogs with Unilateral or Bilateral Stifle Osteoarthritis from Long-Term Medically Managed Cranial Cruciate Ligament Disease. VETERINARY MEDICINE-RESEARCH AND REPORTS 2020; 11:31-38. [PMID: 32215259 PMCID: PMC7082539 DOI: 10.2147/vmrr.s238598] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 02/25/2020] [Indexed: 12/22/2022]
Abstract
Purpose The use of platelet-rich plasma (PRP) to treat canine osteoarthritis has gained support within the scientific community. PRP effects on pain control for degenerative joint disease induced by naturally occurring cranial cruciate ligament instability are limited, particularly in a cohort of dogs with chronic instability and osteoarthritis (>12 months), representing a commonly encountered clinical population that often defaults to medical management. The goal of this study was to assess the effects of a single intra-articular PRP injection into an effected stifle in this cohort, to assess response to treatment, quantitative kinetic data as it relates to percent body weight for peak vertical force (PVF) and vertical impulse (VI) were collected, and symmetry indices related to PVF were determined. Methods Twelve dogs with unilateral or bilateral osteoarthritis with ruptured, non-stabilized cranial cruciate ligaments over 12 months duration were identified. Unilateral injections of 2.5 mL of a PRP preparation into the most severely affected stifle based on kinetic analysis was performed. Repeat pressure-sensitive walkway analysis was conducted monthly for 3 months. Peak vertical force (PVF) and vertical impulse (VI) were normalized to body weight and identified in all four limbs. Previously published symmetry indices regarding PVF were calculated, comparing the treated limb with the contralateral limb, ipsilateral forelimb, and contralateral forelimb. Results After treatment, hind limb symmetry index (SI) regarding PVF showed improved symmetry, suggesting more weight placement at all-time points after injection of the most affected limb (p < 0.01). Further, PVF asymmetry indices assessing contralateral fore (CFL) and hind limb (CHL) as well as ipsilateral forelimb (IFL) revealing a significant decrease from baseline for CHL at week 4 (p = 0.02), but not weeks 8 and 12. The CFL showed decreased differences in symmetry from baseline at each time point (p = 0.03). There were no statistically significant changes in PVF or VI over time in treated dogs. Conclusion A single injection of PRP improved kinetics for minimally 4 weeks with some data suggesting an effect for up to 12 weeks. Therefore, PRP might be a viable therapeutic option for instability and inflammation associated with chronic osteoarthritis due to cranial cruciate ligament disease in the non-surgical patient.
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Affiliation(s)
- Kurt P Venator
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA
| | - Christopher W Frye
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA
| | - Lauri-Jo Gamble
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA
| | - Joseph J Wakshlag
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA
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Alves JC, Santos A, Jorge P, Lavrador C, Carreira LM. A report on the use of a single intra-articular administration of autologous platelet therapy in a naturally occurring canine osteoarthritis model - a preliminary study. BMC Musculoskelet Disord 2020; 21:127. [PMID: 32106842 PMCID: PMC7047415 DOI: 10.1186/s12891-020-3140-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 02/17/2020] [Indexed: 02/07/2023] Open
Abstract
Background Osteoarthritis (OA) represents a significant burden to societies, as it affects quality of life, performance and poses a large healthcare cost. We aimed to describe the use of a single intra-articular (IA) injection of an autologous platelet therapy in the management of osteoarthritis (OA) in a naturally occurring canine model. Methods Fifteen police working dogs with bilateral hip OA were treated with 3 ml of platelet concentrate per hip joint, produced with the V-PET kit. Response to treatment was measured by the Canine Brief Pain Inventory (CBPI, divided in pain interference score – PIS, and Pain Severity Score - PSS), Liverpool Osteoarthritis in Dogs (LOAD), Canine Orthopedic Index (COI, divided in four dimensions: function, gait, stiffness and quality of life - QOL) and the Hudson Visual Analogue Scale (HVAS). Seven different time points were considered: T0 (before treatment), T1 (after 15 days), T2, T3, T4, T5 and T6 (after 1, 2, 3, 4 and 5 months respectively). Results from each evaluation moment were compared with T0 with a Paired Samples T-Test, and a p < 0.05 was set. Results Significant differences were observed at T1 (p < 0.01 for HVAS, PSS, COI, Gait and QOL; p = 0.01 for PIS; p = 0.02 for Function; and p < 0.05 for Stiffness), T2 (p < 0.01 for PSS, PIS and Gait; p = 0.01 for COI; p = 0.02 for HVAS, Function and QOL; and p = 0.04 for Stiffness), T3 (p < 0.01 for HVAS, PSS, PIS, Function and Gait; p = 0.01 for COI; and p = 0.02 for QOL), T4 (p < 0.01 for PSS; p = 0.03 for PIS and Gait), T5 (p < 0.01 for COI, Function and Gait; p = 0.03 for PSS, PIS and Stiffness), T6 (p < 0.01 for PSS, Function and Gait; p = 0.04 for PIS; p < 0.05 for COI) and T7 (p < 0.01 for PSS, Function and Gait; p = 0.01 for COI; and p < 0.05 for PIS). Conclusions Autologous platelet therapy was used without apparent harm in the subjects. A single administration produced significant improvements, which lasted several months, and therefore warrants further study.
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Affiliation(s)
- J C Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal. .,MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554, Évora, Portugal.
| | - A Santos
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal
| | - P Jorge
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771, Lisbon, Portugal
| | - C Lavrador
- MED - Mediterranean Institute for Agriculture, Environment and Development, Instituto de Investigação e Formação Avançada, Universidade de Évora, Pólo da Mitra, Ap. 94, 7006-554, Évora, Portugal
| | - L Miguel Carreira
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), Lisbon, Portugal.,Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV/ULisboa), Lisbon, Portugal.,Anjos of Assis Veterinary Medicine Centre (CMVAA), Barreiro, Portugal
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Cortese L, Christopherson PW, Pelagalli A. Platelet Function and Therapeutic Applications in Dogs: Current Status and Future Prospects. Animals (Basel) 2020; 10:201. [PMID: 31991713 PMCID: PMC7071006 DOI: 10.3390/ani10020201] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 11/16/2022] Open
Abstract
Significant progress has been made in the functional characterization of canine platelets in the last two decades. The role of canine platelets in hemostasis includes their adhesion to the subendothelium, activation, and aggregation, leading to primary clot formation at the site of injury. Studies on canine platelet function and advancements in laboratory testing have improved the diagnosis and understanding of platelet-related disorders as well as the knowledge of the mechanisms behind these diseases. This review focuses on the most recent discoveries in canine platelet structure, function, and disorders; and discusses the efficacy of various tests in the diagnosis of platelet-related disorders. With the relatively recent discovery of angiogenetic and reparative effects of growth factors found in platelets, this review also summarizes the use of canine platelet-rich plasma (PRP) alone or in association with stem cells in regenerative therapy. The characterization of proteomic and lipidomic profiles and development of platelet gene therapy in veterinary species are areas of future study with potential for major therapeutic benefits.
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Affiliation(s)
- Laura Cortese
- Department of Veterinary Medicine and Animal Productions, Division of Internal Medicine, University of Naples Federico II, Via Delpino, 1, 80137 Naples, Italy;
| | - Pete W. Christopherson
- Department of Pathobiology, Auburn University College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA;
| | - Alessandra Pelagalli
- Department of Advanced Biomedical Sciences, University of Naples “Federico II”, 80131 Naples, Italy
- Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy
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36
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Feigin K, Shope B. Use of Platelet-Rich Plasma and Platelet-Rich Fibrin in Dentistry and Oral Surgery: Introduction and Review of the Literature. J Vet Dent 2019; 36:109-123. [DOI: 10.1177/0898756419876057] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Platelet concentrates, mostly represented by platelet-rich plasma and platelet-rich fibrin, have gained significant interest in various medical and oral disciplines because of their potential to stimulate and boost regeneration of hard and soft tissues. Prepared from the patient’s own blood, they have been tested and used in various different surgical fields including oral and maxillofacial surgery. The effects of these biomaterials are described to be a result of the large concentration of platelets which contain a wide range of growth factors. The aim of this article is to introduce the principle and function of these platelet concentrates, to review their preparation, and to provide a comprehensive examination of the published oral and maxillofacial literature on this subject.
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Gamble LJ, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown H, Berthelsen ES, Wakshlag JJ. Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Front Vet Sci 2018; 5:165. [PMID: 30083539 PMCID: PMC6065210 DOI: 10.3389/fvets.2018.00165] [Citation(s) in RCA: 143] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 07/02/2018] [Indexed: 11/13/2022] Open
Abstract
Objectives: The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA). Methods: Single-dose pharmacokinetics was performed using two different doses of CBD enriched (2 and 8 mg/kg) oil. Thereafter, a randomized placebo-controlled, veterinarian, and owner blinded, cross-over study was conducted. Dogs received each of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 h. Each treatment lasted for 4 weeks with a 2-week washout period. Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4. Hematology, serum chemistry and physical examinations were performed at each visit. A mixed model analysis, analyzing the change from enrollment baseline for all other time points was utilized for all variables of interest, with a p ≤ 0.05 defined as significant. Results: Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01). Clinical significance: This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.
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Affiliation(s)
- Lauri-Jo Gamble
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Jordyn M Boesch
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Christopher W Frye
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Wayne S Schwark
- Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Sabine Mann
- Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Lisa Wolfe
- Proteomic and Metabolomic Facility, Colorado State University, Fort Collins, CO, United States
| | - Holly Brown
- Metzger Animal Hospital, State College, PA, United States
| | - Erin S Berthelsen
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
| | - Joseph J Wakshlag
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States
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Matrix metalloproteinases 2 and 9 activity after intra-articular injection of autologous platelet-rich plasma for the treatment of osteoarthritis in dogs. ACTA VET BRNO 2018. [DOI: 10.2754/avb201887020127] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Intra-articular injection of platelet-rich plasma offers a promising potential for treatment of osteoarthritis in dogs. Twenty dogs weighing 25 to 50 kg (mean 38 kg) with unilateral stifle osteoarthritis were used for the study. Fourteen dogs were given intra-articular platelet rich plasma treatment and 6 dogs were used as controls. Double centrifuge method was used to obtain platelet-rich plasma. Radiography and ultrasonography of the affected joint were carried out and scores for lameness severity and pain severity were assigned by the attending clinicians. Synovial fluid was collected under sterile conditions at pre-treatment and on the 1st, 3rd, 5th, 7th, 15thdays, and 4, 8 and 12 weeks after treatment. Gelatin zymography and Enzyme-linked Immunosorbent Assay were used to determine the synovial fluid levels of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9). No adverse effects associated with the injection of the platelet concentrate or saline were observed. Hudson Visual Analog Scale and Canine Brief Pain Inventory scores for all components were non-significantly different between weeks 0, 4, 12 for control dogs. Matrix metalloproteinase-9 was totally and MMP-2 was partially inhibited in the platelet-rich plasma group. In the control group, MMP-9 was partially inhibited during the first month and activation started later. Matrix metalloproteinase-2 was constant in control samples throughout the experimental period. Platelet-rich plasma is a safe and effective method for treatment of dogs with osteoarthritis, possibly more useful for early cases with mild and moderate osteoarthritis. It is suggested that plasma rich platelet should be injected several times at regular intervals instead of a single application.
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Franklin SP, Birdwhistell KE. Assessment of Canine Autologous Conditioned Plasma TM Cellular and Transforming Growth Factor-β1 Content. Front Vet Sci 2018; 5:105. [PMID: 29942808 PMCID: PMC6004536 DOI: 10.3389/fvets.2018.00105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 04/27/2018] [Indexed: 01/09/2023] Open
Abstract
To evaluate (1) the cellular composition of canine ACP™ including using two different preparation protocols with variations on centrifugation time, (2) the effect of different activation protocols on the transforming growth factor (TGF)-β1 content in the ACP, and (3) patient factors that might influence platelet concentration of the ACP. ACP was made with blood from 15 dogs using a manufacturer-recommended protocol[1]. Each ACP sample was divided into three aliquots that were activated with calcium chloride (CaCl2), human γ-thrombin (HGT), or not activated. TGF-β1 was quantified in each aliquot using an ELISA and comparisons among activation protocols were performed using a Skillings-Mack test. Correlations between platelet and TGF-β1 concentration were assessed with a Pearson correlation coefficient. ACP was subsequently prepared from an additional 17 dogs using a slightly modified centrifugation protocol and cellular composition was assessed. Effects of dog age, body weight, and hematocrit were assessed for their potential impact on ACP platelet concentration using a multiple linear regression analysis. The mean increase in platelet concentration in the ACP above that in the whole blood was 1.2× (±std 0.62) and leukocyte concentration was a mean of 26% (0.37) that in the whole blood using the standard protocol. There was a significant (p < 0.01) effect of activation on TGF-β1 concentrations with mean concentrations of 4,538 (2,317), 14,948 (13,784), and 14,096 (15,210) pg/ml in aliquots that were not activated or were activated with thrombin or CaCl2 respectively. There were significant correlations between the platelet concentration and TGF-β1 concentration in aliquots that were activated with either thrombin (r = 0.66; p < 0.01) or CaCl2 (r = 0.86, p < 0.0001). The mean increase in platelet concentration was 1.4× (0.62) and the leukocyte concentration was 0.28× (0.13) that in whole blood using the modified ACP preparation protocol. Dog age, body weight, and hematocrit were not significant predictors of ACP platelet concentration. These data show that on average this preparation protocol produces a mildly platelet-concentrated, leukoreduced platelet-rich plasma. Intentional activation had a significant effect on TGF-β1 concentrations with use of both CaCl2 and thrombin resulting in higher TGF-β1 concentrations than that obtained in samples that are not activated.
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Affiliation(s)
- Samuel P Franklin
- Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, United States.,Regenerative Bioscience Center, University of Georgia, Athens, GA, United States
| | - Kate E Birdwhistell
- Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, United States.,Regenerative Bioscience Center, University of Georgia, Athens, GA, United States
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Bogers SH. Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know. Front Vet Sci 2018; 5:70. [PMID: 29713634 PMCID: PMC5911772 DOI: 10.3389/fvets.2018.00070] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Accepted: 03/23/2018] [Indexed: 12/19/2022] Open
Abstract
Biological cell-based therapies for the treatment of joint disease in veterinary patients include autologous-conditioned serum, platelet-rich plasma, and expanded or non-expanded mesenchymal stem cell products. This narrative review outlines the processing and known mechanism of action of these therapies and reviews current preclinical and clinical efficacy in joint disease in the context of the processing type and study design. The significance of variation for biological activity and consequently regulatory approval is also discussed. There is significant variation in study outcomes for canine and equine cell-based products derived from whole blood or stem cell sources such as adipose and bone marrow. Variation can be attributed to altering bio-composition due to factors including preparation technique and source. In addition, study design factors like selection of cases with early vs. late stage osteoarthritis (OA), or with intra-articular soft tissue injury, influence outcome variation. In this under-regulated field, variation raises concerns for product safety, consistency, and efficacy. Cell-based therapies used for OA meet the Food and Drug Administration’s (FDA’s) definition of a drug; however, researchers must consider their approach to veterinary cell-based research to meet future regulatory demands. This review explains the USA’s FDA guidelines as an example pathway for cell-based therapies to demonstrate safety, effectiveness, and manufacturing consistency. An understanding of the variation in production consistency, effectiveness, and regulatory concerns is essential for practitioners and researchers to determine what products are indicated for the treatment of joint disease and tactics to improve the quality of future research.
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Affiliation(s)
- Sophie Helen Bogers
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States
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Rossi F, Cancedda S, Leone VF, Rohrer Bley C, Laganga P. Megavoltage Radiotherapy for the Treatment of Degenerative Joint Disease in Dogs: Results of a Preliminary Experience in an Italian Radiotherapy Centre. Front Vet Sci 2018; 5:74. [PMID: 29692993 PMCID: PMC5903029 DOI: 10.3389/fvets.2018.00074] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 03/26/2018] [Indexed: 12/26/2022] Open
Abstract
The aim of the study was to evaluate the efficacy and toxicity of a low-dose radiotherapy treatment in dogs with osteoarthritis (OA). Inclusion criteria were dogs affected by OA of one or multiple joints, with lameness, previously treated with medical therapy and referred for radiotherapy because of chronic unresponsive pain. After suspension of medical therapy, dogs underwent external beam radiotherapy treatments delivered in three fractions of 2 Gy each. Four of these dogs had one (three dogs) to four (one dog) additional courses of radiation. Medical records were reviewed and follow-up information was collected by clinical recheck and owners interview. Twenty-five dogs matched the inclusion criteria; among them, 21 had one course of RT and 4 underwent multiple treatments, respectively 218, 266, 39, and 1,384 days after the first treatment. Clinical improvement was observed in 92% of patients with median benefit duration of 356 days after the first treatment, and 418 days after the second treatment. No side effects were recorded. In this group of patients, radiotherapy was effective, well tolerated, and repeatable, leading to an improvement of quality of life in dogs with degenerative joint disease unresponsive to medical treatments.
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Affiliation(s)
- Federica Rossi
- Centro Oncologico Veterinario, Sasso Marconi, Italy.,Clinica Veterinaria dell'Orologio, Sasso Marconi, Italy
| | | | | | - Carla Rohrer Bley
- Centro Oncologico Veterinario, Sasso Marconi, Italy.,Division of Radiation Oncology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
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Vilar JM, Manera ME, Santana A, Spinella G, Rodriguez O, Rubio M, Carrillo JM, Sopena J, Batista M. Effect of leukocyte-reduced platelet-rich plasma on osteoarthritis caused by cranial cruciate ligament rupture: A canine gait analysis model. PLoS One 2018; 13:e0194752. [PMID: 29554150 PMCID: PMC5858837 DOI: 10.1371/journal.pone.0194752] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 03/08/2018] [Indexed: 12/27/2022] Open
Abstract
The goal of this study was to objectively assess the effect of a platelet-rich plasma (PRP) derivate in English bulldogs with stifle degenerative joint disease secondary to cranial cruciate ligament rupture (CCLR). We used a force platform and affixed electrogoniometers to measure peak vertical force (PVF), vertical impulse (VI), stance time (ST), and angular range of motion (AROM), from 12 lame client-owned English bulldogs with post-CCLR stifle joint abnormalities. The 12 affected subjects were treated with 4 intra-articular injections of PRP, at 30-day intervals. Ten untreated, sound English bulldogs were used as a reference group. Clinical outcomes were evaluated using a linear mixed effects model. Mean values of PVF, VI, ST, and AROM were improved within the first 3 months post-treatment in the CCLR group, with mean measured changes increasing to maximum 4.56% body weight gain, 1.5% body weight/second, 0.07 seconds, and 6.18 degrees, respectively. The effects declined progressively after the treatment interval, ending at nearly initial levels after 6 months. This study demonstrates that dogs with CCLR treated with intra-articular PRP had improved PVF, VI, ST, and AROM over time; the duration of effect was waning by the end of the post-treatment period.
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Affiliation(s)
- José M. Vilar
- Departamento de Patología Animal, Facultad de Veterinaria de la Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas, Las Palmas, Spain
- Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria, Juan de Quesada 30, Las Palmas de Gran Canaria, Las Palmas, Spain
- * E-mail:
| | - Maria E. Manera
- Departamento de Patología Animal, Facultad de Veterinaria de la Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas, Las Palmas, Spain
| | - Angelo Santana
- Departamento de Patología Animal, Facultad de Veterinaria de la Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas, Las Palmas, Spain
| | - Giuseppe Spinella
- Dipartimento di Science Mediche Veterinarie, Facoltà di Veterinaria de la Università di Bologna, Via Tolara di sopra 50, Ozzano, Bologna, Italy
| | - Oliver Rodriguez
- Departamento de Patología Animal, Facultad de Veterinaria de la Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas, Las Palmas, Spain
| | - Mónica Rubio
- Departamento de Medicina y Cirugía Animal, Universidad CEU Cardenal Herrera, C/ Tirant lo Blanc, 7, Alfara del Patriarca, Valencia, Spain
| | - José M. Carrillo
- Departamento de Medicina y Cirugía Animal, Universidad CEU Cardenal Herrera, C/ Tirant lo Blanc, 7, Alfara del Patriarca, Valencia, Spain
| | - Joaquín Sopena
- Departamento de Medicina y Cirugía Animal, Universidad CEU Cardenal Herrera, C/ Tirant lo Blanc, 7, Alfara del Patriarca, Valencia, Spain
| | - Miguel Batista
- Departamento de Patología Animal, Facultad de Veterinaria de la Universidad de Las Palmas de Gran Canaria, Trasmontaña S/N, Arucas, Las Palmas, Spain
- Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria, Juan de Quesada 30, Las Palmas de Gran Canaria, Las Palmas, Spain
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Alves JC, Santos AM, Jorge PI. Effect of an Oral Joint Supplement When Compared to Carprofen in the Management of Hip Osteoarthritis in Working Dogs. Top Companion Anim Med 2017. [PMID: 29525231 DOI: 10.1053/j.tcam.2017.10.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The goal of this study was to evaluate the effectiveness of an oral joint supplement in working dogs with hip osteoarthritis compared with a positive control group (CG). Fifteen animals were divided in treatment group (TG, n = 10) and CG (n = 5). To TG a commercially available joint supplement, containing glucosamine HCl, chondroitin sulphate, and hyaluronic acid was given for 40 days and a 70-day course of a placebo, to be administered as if it was carprofen. The CG received carprofen for 70 days, and a placebo to be administered as the joint supplement. Response to treatment, measured by the canine brief pain inventory (CBPI) and the Hudson visual analog scale, was evaluated before treatment (T0), after 15 days (T1) and 1 (T2), 2 (T3), 3 (T4), 4 (T5), and 5 (T6) months. With CBPI, no differences were found in pain interference score and pain severity score between TG and CG throughout or when comparing results within groups. Individual results were considered successful in a maximal of three dogs of the TG by T3 (30%) and 1 in CG (25%). With Hudson visual analog scale, improvements where registered with individual results, for 40%-50% of the animals in TG and 60%-80% of cases in CG. The oral joint supplement and carprofen produced some improvements in individual scores but where unable to do so when overall results were considered. Each of these options may not be able, by itself, to fully address the demands of a working dog with joint disease and related pain.
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Affiliation(s)
- João Carlos Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana, Lisbon, Portugal; CINAMIL-Military Academy Research Center, Lisbon, Portugal.
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Mickelson MA, Vo T, Piazza AM, Volstad NJ, Nemke BW, Muir P. Influence of trial repetition on lameness during force platform gait analysis in a heterogeneous population of clinically lame dogs each trotting at its preferred velocity. Am J Vet Res 2017; 78:1284-1292. [PMID: 29076365 DOI: 10.2460/ajvr.78.11.1284] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To determine variance effects influencing ground reaction forces (GRFs) in a heterogeneous population of lame dogs during trotting. ANIMALS 30 client-owned dogs with thoracic limb lameness and 31 dogs with pelvic limb lameness. PROCEDURES GRFs, velocity, height at the dorsal aspect of the scapulae (ie, withers), and shoulder height were obtained. Each dog was trotted across a force platform at its preferred velocity. Variance effects for 12 velocity and associated relative velocity (V*) ranges were examined. RESULTS Individual dog, velocity, V*, and limb significantly influenced GRFs. Withers height V* ranges were associated with small variance in GRFs, but all absolute and V* ranges were associated with significant effects for all 4 limbs and both types of lameness. Significant changes in lame limb GRFs and velocity in ipsilateral trials in dogs with thoracic limb and pelvic limb lameness were evident with trial repetition. Withers height V* range of 0.55 to 0.93 captured a large proportion of trials (> 90%) in dogs with thoracic limb or pelvic limb lameness, with limited effects on peak vertical force and vertical impulse. CONCLUSIONS AND CLINICAL RELEVANCE Trial repetition caused alterations to GRFs and subject velocity that may have confounded assessment of lameness, which supported the concept that a priori selection of a velocity or V* range for force platform gait analysis should use a range that captures valid trials efficiently while minimizing GRF variance. These ranges typically would span the preferred velocity of subject dogs, such as withers height V* of 0.55 to 0.93.
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Abstract
Hip dysplasia (HD) is a common orthopedic condition seen in small animal patients that leads to osteoarthritis of the coxofemoral joint. The disease can be managed conservatively or surgically. The goals of surgical treatment in the immature patient are to either prevent the clinical signs of HD or to prevent or slow the progression of osteoarthritis. In mature patients surgery is used as a salvage procedure to treat debilitating osteoarthritis. Conservative management can be used in dogs with mild or intermittent clinical signs and includes nutritional management and weight control, exercise modification, physical rehabilitation, pain management and disease-modifying agents.
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Affiliation(s)
- Tisha A M Harper
- Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, 1008 West Hazelwood Drive, Urbana, IL 61802, USA.
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Alves JC, Santos AM. Evaluation of the Effect of Mesotherapy in the Management of Osteoarthritis-Related Pain in a Police Working Dog Using the Canine Brief Pain Inventory. Top Companion Anim Med 2017; 32:41-43. [PMID: 28750790 DOI: 10.1053/j.tcam.2017.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 06/30/2017] [Accepted: 07/01/2017] [Indexed: 11/11/2022]
Abstract
CASE DESCRIPTON A 9-year-old, 33.4kg (73.63Lb) male entire drug detection Labrador Retriever Dog was presented with an history of constant lameness from the right thoracic limb, aggravated with exercise and work. CLINICAL FIDINGS Clinical examination revealed mild signs of pain on the manipulation of the elbow joint, with reduced range of motion on the end feel of joint flexion and extension and crepitation. Radiographic examination of the right elbow joint revealed severe, chronic osteoarthritis, with osteophyte formation on the humeral epicondyles and articular margin of the distomedial humerus, with a narrowed joint space, and osteophytes on the proximal radius, proximomedial ulna, and anconeal process. TREATMENT AND OUTCOME A solution comprised of a combination of lidocaine, thiocolchicoside, and piroxicam was prepared and applied around the right elbow joint. The animal was rested for 3 days and normal work load was introduced over a 5-day period. The CPBI was completed by the trainer before treatment (T0), 14 days (T1), 1 (T2), 2 (T3), 3 (T4), 4 (T5), 5 (T6), and 6 (T7) months after treatment. Following the mesotherapy session, pain score results consistently declined until the 3-month evaluation moment. At the 6-month follow-up evaluation, values have risen to near baseline values. No side effects were recorded. CLINICAL RELEVANCE Mesotherapy produced significant reduction of pain score results, as measure by the CBPI, and may be a promising treatment option for canine osteoarthritis-related pain. Further studies are required.
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Affiliation(s)
- João Carlos Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana, Lisbon, Portugal; CINAMIL-Military Academy Research Center, Lisbon, Portugal.
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Franklin SP, Birdwhistell KE, Strelchik A, Garner BC, Brainard BM. Influence of Cellular Composition and Exogenous Activation on Growth Factor and Cytokine Concentrations in Canine Platelet-Rich Plasmas. Front Vet Sci 2017; 4:40. [PMID: 28424777 PMCID: PMC5380674 DOI: 10.3389/fvets.2017.00040] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 03/07/2017] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVE The purposes of this study were to (1) evaluate correlations among platelet, leukocyte, growth factor, and cytokine concentrations in canine platelet-rich plasmas (PRPs) produced from five different canine PRP-concentrating systems and (2) compare the effects of different activation protocols on platelet activation and growth factor release from one of these PRPs. METHODS PRP was made using blood from 15 dogs and each of 5 different PRP systems in a cross-over design. Complete blood counts were performed to quantify platelet and leukocyte concentrations. PRPs were activated, or not, according to manufacturer instructions, and transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor, and tumor necrosis factor-alpha (TNF-α) were quantified. Differences among platelet, leukocyte, and growth factor concentration were compared among the different systems. Correlations between platelet and anabolic growth factor concentrations were assessed. Subsequently, PRP was made from 12 additional dogs using one of the devices. Each PRP was divided into three aliquots that were activated with calcium chloride (CaCl2), human γ-thrombin (HGT), or not activated. Expression of CD62P and platelet-bound fibrinogen (CAP1) was quantified for each activation group. Concentrations of TGF-β1, PDGF-BB, and TNF-α were also quantified for each activation group and a fourth group that was frozen/thawed. Differences among activation groups were assessed by a Friedman test. RESULTS There were statistically significant differences among the PRPs made with difference devices with regard to platelet, leukocyte, TGF-β1, and PDGF-BB concentrations (p < 0.0001). There were weak to moderate correlations (R2 = 0.07-0.58) between platelet and anabolic growth factor concentrations but it appeared that activation had a greater effect on growth factor concentration than did cellular composition. Intentional platelet activation significantly increased CD62P and CAP1 expression as well as TGF-β1 and PDGF-BB concentrations in the one PRP in which all activation methods were assessed. Activation with HGT resulted in the greatest platelet activation, and CaCl2 and freeze/thaw elicited moderate increases in either growth factor release or CD62P and CAP1 expression. CONCLUSION There are positive correlations between platelet and anabolic growth factor concentrations in canine PRPs. However, intentional platelet activation has a greater effect on growth factor delivery than platelet concentration. Thrombin provides more robust activation than CaCl2.
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Affiliation(s)
- Samuel P Franklin
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.,Regenerative Bioscience Center, University of Georgia, Athens, GA, USA
| | - Kate E Birdwhistell
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
| | - Alena Strelchik
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
| | - Bridget C Garner
- Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
| | - Benjamin M Brainard
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
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Allen MJ, Hankenson KD, Goodrich L, Boivin GP, von Rechenberg B. Ethical use of animal models in musculoskeletal research. J Orthop Res 2017; 35:740-751. [PMID: 27864887 DOI: 10.1002/jor.23485] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 11/16/2016] [Indexed: 02/04/2023]
Abstract
The use of animals in research is under increasing scrutiny from the general public, funding agencies, and regulatory authorities. Our ability to continue to perform in-vivo studies in laboratory animals will be critically determined by how researchers respond to this new reality. This Perspectives article summarizes recent and ongoing initiatives within ORS and allied organizations to ensure that musculoskeletal research is performed to the highest ethical standards. It goes on to present an overview of the practical application of the 3Rs (reduction, refinement, and replacement) into experimental design and execution, and discusses recent guidance with regard to improvements in the way in which animal data are reported in publications. The overarching goal of this review is to challenge the status quo, to highlight the absolute interdependence between animal welfare and rigorous science, and to provide practical recommendations and resources to allow clinicians and scientists to optimize the ways in which they undertake preclinical studies involving animals. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:740-751, 2017.
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Affiliation(s)
- Matthew J Allen
- Department of Veterinary Medicine, Surgical Discovery Centre, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom
| | | | | | - Gregory P Boivin
- Wright State University, Dayton, 45435, Ohio.,Veterans Affairs Medical Center, Cincinnati, 45220, Ohio
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Walton B, Innes J, Lascelles BDX, Belshaw Z. Validated Outcomes Measures for Canine Osteoarthritis. Vet Surg 2017; 46:341-342. [PMID: 28314073 DOI: 10.1111/vsu.12636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 01/04/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Ben Walton
- RCVS Specialist in Small Animal Surgery (Orthopaedics), Chestergates Veterinary Specialists, Chester, United Kingdom
| | - John Innes
- RCVS Specialist in Small Animal Surgery (Orthopaedics), Chestergates Veterinary Specialists, Chester, United Kingdom
| | - B Duncan X Lascelles
- Comparative Pain Research, NC State College of Veterinary Medicine, Raleigh, North Carolina
| | - Zoe Belshaw
- European Recognized Specialist in Small Animal Internal Medicine Centre for Evidence-based Veterinary Medicine, University of Nottingham, UK
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50
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Bertone AL, Reisbig NA, Kilborne AH, Kaido M, Salmanzadeh N, Lovasz R, Sizemore JL, Scheuermann L, Kopp RJ, Zekas LJ, Brokken MT. Equine Dental Pulp Connective Tissue Particles Reduced Lameness in Horses in a Controlled Clinical Trial. Front Vet Sci 2017; 4:31. [PMID: 28344975 PMCID: PMC5344919 DOI: 10.3389/fvets.2017.00031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 02/20/2017] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE To assess if injection of allogeneic dental pulp tissue particles would improve lameness in horses with naturally occurring osteoarthritis (OA) or soft tissue (ST) injury. DESIGN Prospective, randomized, blinded, and controlled clinical trial and client survey assessment. ANIMALS Forty lame client-owned horses. PROCEDURES Sterile dental pulp, recovered from otherwise healthy foals that perish during dystocia, was processed under good manufacturing processing to produce mechanically manipulated, unexpanded pulp tissue particles containing viable cells surrounded in extracellular matrix. Forty lame client-owned horses with confirmed OA (n = 20), or ST injury (desmitis or tendonitis) received a 2 mL intra-articular (n = 20 OA) or intra-lesional (n = 20) injection of control transport vehicle (n = 20) or 10 × 106 dental pulp tissue particles (n = 20). Acclimatized horses had baseline measurements performed and were then injected on day 0. Horses were treadmill exercised for 2 weeks, evaluated by clinical parameters, lameness score, edema (score and circumference), pain on flexion (OA) or pressure (ST), and clients' scores for pain and discomfort before and through 45 days after pulp injection. Twenty horses were available for >2.5-year follow-up. RESULTS Pulp-treated horses showed decrease in lameness compared to baseline (P < 0.009) or placebo controls (P < 0.013) for at least 2 weeks. Client assessments of comfort were improved between before and 45 days after pulp injection (P < 0.001). Clinical improvement with ST injury was significantly greater than OA (P < 0.001). At >2.5-year follow-up, at least 10 horses were in work. CONCLUSION AND CLINICAL RELEVANCE Dental pulp tissue particles can be considered as a treatment option for equine lameness due to OA, desmitis, or tendonitis.
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Affiliation(s)
- Alicia L. Bertone
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Nathalie A. Reisbig
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Allison H. Kilborne
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Mari Kaido
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Navid Salmanzadeh
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Rebecca Lovasz
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Joy L. Sizemore
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Logan Scheuermann
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Rosalind J. Kopp
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Lisa J. Zekas
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Matthew T. Brokken
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
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