Restigen is referenced as GPS III in some of the below clinical sources.
Equine autologous platelet concentrates: A comparative study between different available systems
L. N. HESSEL, G. BOSCH, P. R. VAN WEEREN and J.-C. IONITA*†
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands †Large Animal Clinic for Surgery, Faculty of Veterinary Medicine, University of Leipzig, Germany.
*Correspondence email: ; Received: 03.07.13; Accepted: 06.04.14
Reasons for performing study: Autologous platelet concentrates (APCs) are being used increasingly in horses to enhance regeneration in tissues that have poor natural healing capabilities. Numerous APC systems, which are based on different preparation techniques and were originally developed for human patients, are now routinely used in equine cases. However, preliminary process validation and adequate in vitro biochemical characterization of most
of these systems do not exist for horses.
Objectives: To compare hematological findings and growth factor concentrations of equine APCs obtained with 4 commercially available systems and a noncommercial double-centrifugation technique.
Study design: Nonrandomized in vitro experiment.
Methods: Blood samples from 6 horses were processed to produce APCs using one equine-specific filtration-based and 4 different centrifugation-based techniques. Platelet, leucocyte, platelet-derived growth factor-BB and transforming growth factor-β1 concentrations were measured in all APCs, and their respective enrichment factors were compared.
Results: Mean platelet concentration increased in all systems in comparison to baseline; however, the mean enrichment factor, which ranged from 130% to 527% depending on the APC, was statistically significant in only 2 products. One method reduced total leucocyte counts to 9% of the baseline value, while the others had a mean fold increase varying from 116 to 663% of the baseline. Differential leucocyte count also differed between the products. Moreover, the various systems had significantly different mean growth factor enrichments (184–1255% for platelet-derived growth factor-BB and 93–560% for transforming
Conclusions: Hematological and biochemical characteristics varied markedly among 5 techniques used in the field to produce APCs in horses. These discrepancies could have an impact on clinical outcomes, and further studies are needed to determine their influence on the quality of tissue regeneration. Clinicians should not rely on the manufacturers’ data relating to human patients to select the most appropriate method for horses.
Keywords: horse; platelet concentrates; growth factors; platelet-rich plasma; tissue regeneration; comparison.
Effects of Platelet-Rich Plasma on the Quality of Repair of Mechanically Induced Core Lesions in Equine Superficial Digital Flexor Tendons: A Placebo-Controlled Experimental Study
Gerco Bosch,1 Hans T. M. van Schie,1,2 Mark W. de Groot,3 Jennifer A. Cadby,1,2 Chris H. A. van de Lest,1,4 Ab Barneveld,1 P. Rene van Weeren1
1Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, the Netherlands, 2Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands, 3Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands, 4Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
Received 11 March 2009; accepted 9 July 2009
Published online 27 August 2009 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jor.20980
ABSTRACT: Tendon injuries are notorious for their slow and functionally inferior healing. Intratendinous application of platelet-rich plasma (PRP) has been reported to stimulate the repair process of tendon injuries, but there is little conclusive evidence for its effectiveness.A placebo-controlled experimental trial was performed to test the hypothesis that a single intratendinous PRP treatment enhances the quality of tendon repair, as evidenced by improved biochemical, biomechanical, and histological tissue properties. In six horses, tendon lesions were created surgically in the Superficial Digital Flexor Tendons (SDFT) of both front limbs, one of which was treated with PRP and the other with saline. After 24 weeks, the tendons were harvested for biochemical, biomechanical, and histological evaluations. Collagen, glycosaminoglycan, and DNA content (cellularity) was higher in PRP-treated tendons (p.0.039, 0.038, and 0.034, respectively). The repair tissue in the PRP group showed a higher strength at failure (p.0.021) and Elastic Modulus (p.0.019). Histologically, PRP-treated tendons featured better organization of the collagen network (p.0.031) and signs of increased metabolic activity (p.0.031). It was concluded that PRP increases metabolic activity and seems to advance maturation of repair tissue over non-treated experimentally induced tendon lesions, which suggests that PRP might be beneficial in the treatment of clinical tendon injuries. 2009 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 28:211–217, 2010
Keywords: platelet-rich plasma (PRP); tendon; collagen; histology; repair
The effect of platelet-rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions
G. Bosch1, M. Moleman1, A. Barneveld1, P. R. van Weeren1, H. T. M. van Schie1
1Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, 2Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands Corresponding author: G. Bosch, Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. Tel: 131 30 2531350, Fax: 131 30 2537970, E-mail:
Accepted for publication 23 November 2009
ABSTRACT: The repair process of tendon injuries, which are common in both human and equine athletes, is slow and the quality of the repair tissue is often inferior to the original tendon tissue, which frequently leads to re-injury. The relatively poor vascularization of tendons is considered to be one of the reasons for their limited healing potential. Recently, platelet-rich plasma (PRP), an autologous concentrate of platelets, rich in growth factors, has been shown to enhance the repair process of injured tendons. This effect has been ascribed to the high levels of growth factors in PRP, several of which are known to be involved in tendon repair. Among many other growth factors, the vascular endothelial growth factor, a powerful stimulator of angiogenesis, is abundantly present in PRP, suggesting that enhancement of neovascularization might be one of the working mechanisms. In this study, the effect of PRP on neovascularization was studied in experimentally induced tendon injuries using color Doppler ultrasonography and immunological staining of Factor VIII. PRP induced significantly more neovascularization than the placebo treatment until at least 23 weeks after treatment, as detected by both Doppler ultrasonography and Factor VIII staining. Neovascularization might be one of the explanations for the long-lasting effect of a single intratendinous treatment with PRP.
Computerised analysis of standardized ultrasonographic images to monitor the repair of surgically created core lesions in equine superficial digital flexor tendons following treatment with intratendinous platelet-rich plasma or placebo
Gerco Bosch a,*, P. René van Weeren a, Ab Barneveld a, Hans T.M. van Schie a,b
a Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
b Orthopaedic Research Laboratory, Department Orthopaedic Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
ABSTRACT: The effectiveness of new therapies to treat tendon injuries is difficult to determine and is often based on semi-quantitative methods, such as grey level analysis of ultrasonographic images or subjective pain scores. The alternatives are costly and long-lasting end-stage studies using experimental animals. In this study, a method of ultrasonographic tissue characterization (UTC), using mathematical analysis of contiguous transverse ultrasonographic images, was used for intra-vital monitoring of the healing trajectory of standardized tendon lesions treated with platelet-rich plasma (PRP) or placebo. Using UTC it was possible to detect significant differences between the groups in the various phases of repair. At end stage, over 80% of pixels showed correct alignment in the PRP group, compared with just over 60% in the placebo group (P < 0.05). UTC also showed significant differences in the course of the healing process between PRP treated and placebo-treated animals throughout the experiment. It was concluded that computerized analysis of ultrasonographic images is an excellent tool for objective longitudinal monitoring of the effects of treatments for superficial digital flexor tendon lesions in horses.
Clinical effects of pre-breeding intrauterine PRP in the mare
Lauren R. Pasch1, Andrew R. Schmidt1, William King2
1Wisconsin Equine Clinic & Hospital, Oconomowoc, WI; 2Owl Manor Medical, Warsaw, IN
ABSTRACT: Platelet-rich plasma (PRP) is being used with increasing frequency in both human and veterinary medicine. By concentrating platelets, growth factors are recruited to aid in tissue healing and repair. In women, intrauterine PRP has been shown to improve endometrial receptivity. In mares, a limited number of studies have focused on the treatment of subfertile mares with intrauterine autologous blood products. Our aim was to examine the safety and efficacy of intrauterine administration of autologous PRP prepared with a commercial platelet isolation device (Restigen PRP). We hypothesized that the treatment would be both safe and effective in addressing intrauterine inflammation, as based on the frequency of adverse events, intrauterine fluid grade and pregnancy rate following treatment. Notably, we elected to focus on clinical endpoints rather than histologic or cytologic evaluations, and used thawed frozen semen as opposed to fresh or cooled transported semen. In this clinical-based crossover study, inclusion criteria were failure to achieve pregnancy after artificial insemination with frozen semen, absence of clinical evidence of infectious endometritis, and normal physical exam parameters. Eighteen mares of various breed, age and parity were enrolled in the study. Each mare served as her own control and was bred to the same stallion as the previous cycle. Breeding management was performed in a routine manner. Autologous PRP was prepared by an experienced operator using Restigen PRP kits and uterine body infusion was performed 12-48 hours prior to artificial insemination. Post insemination, intrauterine fluid was graded via transrectal ultrasound using a predetermined scale based on volume and echogenicity. Pregnancy status was determined via transrectal ultrasound examination at 13-16 days post ovulation or via embryo flush performed 7-8 days post ovulation. No adverse events were recorded in association with intrauterine infusion of PRP. Data were analyzed using nonparametric tests with a significance defined at p < 0.05. There was no statistically significant difference in post-breeding intrauterine fluid score between treatment and control groups. Post-breeding intrauterine fluid score was improved in 7/18 mares (39%) and was unchanged in 6/18 (33%). There was a significant effect of treatment on pregnancy rate, as 11/18 mares (61%) became pregnant on the treated cycle as opposed to 0/18 (0%) on the control cycle. The results of this study indicate that intrauterine infusion of autologous PRP prepared with a commercial platelet isolation device in the peri-ovulatory period is a safe procedure, and was associated with improved breeding outcomes in this population of mares. To better determine efficacy, further studies are in progress to differentiate these results from those of second cycle pregnancy rates without the use of PRP.
Keywords: Mare, platelet-rich plasma, frozen semen, artificial insemination, safety, inflammation