Joaquin Sopena

Assessment of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells in osteoarthritic dogs using a double blinded force platform analysis

BackgroundRegenerative medicine using Mesenchymal Stem Cells (MSC) alone or combined with Plasma Rich in Growth Factors (PRGF) is a rapidly growing area of clinical research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify and quantify the efficacy of different therapeutic strategies for the treatment of OA in dogs including MSC associated to PRGF, but never with AD-MSC alone.The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA.ResultsTen lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved within the first three months post-treatment in the OA group, increasing 9% and 2.5% body weight, respectively, at day 30. After this, the effect seems to decrease reaching initial values.ConclusionIntraarticular ADMSC therapy objectively improved limb function in dogs with hip OA. The duration of maximal effect was less than 3 months.

Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors

Purpose: The aim of this study was to compare the efficacy and safety of a single intra-articular injection of adipose mesenchymal stem cells (aMSCs) versus plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in dogs with hip osteoarthritis (OA). Methods: This was a randomized, multicenter, blinded, parallel group. Thirty-nine dogs with symptomatic hip OA were assigned to one of the two groups, to receive aMSCs or PRGF. The primary outcome measures were pain and function subscales, including radiologic assessment, functional limitation and joint mobility. The secondary outcome measures were owners’ satisfaction questionnaire, rescue analgesic requirement and overall safety. Data was collected at baseline, then, 1, 3 and 6 months post-treatment. Results: OA degree did not vary within groups. Functional limitation, range of motion (ROM), owner’s and veterinary investigator visual analogue scale (VAS), and patient’s quality of life improved from the first month up to six months. The aMSCs group obtained better results at 6 months. There were no adverse effects during the study. Our findings show that aMSCs and PRGF are safe and effective in the functional analysis at 1, 3 and 6 months; provide a significant improvement, reducing dog’s pain, and improving physical function. With respect to basal levels for every parameter in patients with hip OA, aMSCs showed better results at 6 months.

Static Posturography: A New Perspective in the Assessment of Lameness in a Canine Model.

The aim of this study was to assess the static posturography in dogs as a useful tool for diagnosis of lameness by means of the use of a pressure platform. For this purpose, a series of different parameters (pressure distribution, area of support, mean pressure, maximum pressure and statokinesiograms) were obtained from five lame dogs with unilateral elbow osteoarthritis treated with plasma rich in growth factors. Data were obtained before and 3 months after treatment, and results were compared with a control group of sound dogs of similar conformation. Significant differences were found in the above mentioned parameters between sound and lame limbs. Improvement after 3 months of treatment was also detected, demonstrating that this multi-parametric technique is an effective and reliable method for the assessment of lameness in dogs.

Therapeutic doses of plasma rich in growth factors cannot provoke cancer by means of the IGF-1 pathway or inflammation in dogs

ABSTRACT A potential relationship between an increased risk of cancer and increased levels of serum insulin-like growth factor-1 (IGF-1), and presence of cancer and high levels of C-reactive protein (CRP) has been previously reported. This study evaluated the influence of a single intramuscular injection of plasma rich in growth factors (PRGF) on serum concentrations of IGF-1 and CRP in dogs. Two groups of eight healthy beagles were injected with two different doses of PRGF in lumbar muscles. For each treatment, IGF-1 and CRP were analysed from blood samples obtained at baseline and the following three days post injection. No differences were found when IGF-1 and CRP were compared among times in the two protocols. Local application of PRGF at clinical doses did not cause significant changes in systemic concentrations of IGF-1 or detectable inflammation.

Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis

The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.

Effect of leukocyte-reduced platelet-rich plasma on osteoarthritis caused by cranial cruciate ligament rupture: A canine gait analysis model

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.

Ultrasonographic evaluation of cross-sectional area of tarsal ligaments in Standardbred Trotter Horses

ABSTRACT Ultrasound evaluations of the cross-sectional area (CSA) in the tarsal region of Standardbred Trotter Horses (STH) have been previously reported for tendons but not for ligaments. The objective of this study was to identify normal ultrasonographic CSAs in the tarsal ligaments of STH. Transverse echographic scans of ligaments at five tarsal levels from proximal to distal direction were recorded in 25 healthy STH. All images were recorded, and the CSA measurements (mean ± SD) were determined. The widest structure resulted in the long plantar ligament (LPL) at distal portion of the astragalus, and the smallest was the long medial collateral ligament (LMCL) at the medial malleolus of the tibia. Long collateral ligaments (LCL) increased their CSA at the level of their distal insertions, while LPL reached the maximum CSA in the middle of its length. Although this report was limited due to its retrospective design, it is the opinion of the authors that the normal CSAs investigated in this paper could function as a reference guide when tarsal pathological conditions are suspected in STH.

Ultrasonographic measurements on normal tarsocrural articular recesses in the Standardbred Trotter horse

ABSTRACT The aim of this study was to provide reference measurements from the three tibiotarsal synovial recesses (plantarolateral, plantaromedial, and dorsomedial) from both right and left sound equine hock joints. For this study, proximodistal and plantarodorsal (PLD) diameters were ultrasonographically obtained from the synovial recesses of 24 sound Standardbred Trotter horses. A comparison between right and left limb measurements was also made. The dorsomedial recess has shown a variable PLD diameter (0.11–0.90 cm), although the plantarolateral recess has shown the most variable dimensions (0.3–1.5 cm). In many cases, great differences have been found between two tarsi within the same horse; in contrast, the plantaromedial recess of the tarsocrural joint has a more homogeneous PLD diameter (0.6–0.9 cm). Ultimately, the assessed echographic limits for the studied tarsal structures could serve to accurately evaluate the pathological variations for this breed.

Histological, cytogenetic and endocrine evaluation in twenty-five unilateral cryptorchid horses

ABSTRACT Data from 49 horses (25 unilateral cryptorchid and 24 as control group) are reported to determine macroscopic and microscopic characteristics of the testes, as well as to characterize their karyotype and hormonal levels. Histology showed that only Sertoli cells were found in the lumen of the seminiferous tubules of the cryptorchid testes, while spermatogenesis in the scrotal testes resulted normal. Cytogenetic evaluation showed that all cryptorchid horses were normal males (2n = 64, XY). In addition, the lower testosterone production observed in cryptorchid horses was associated to the smaller size of the retained testicle as well as to the lower number of Leydig cells adjacent to the seminiferous tubules. This study confirmed that a simple determination of plasma testosterone levels was enough to differentiate between non-breeding stallions, cryptorchid and castrated animals, avoiding the administration of hCG.

Adipose-Derived Mesenchymal Stem Cells: Are They a Good Therapeutic Strategy for Osteoarthritis?

Osteoarthritis (OA) is a major cause of disability in elderly population around the world. More than one-third of people over 65 years old shows either clinical or radiological evidence of OA. There is no effective treatment for this degenerative disease, due to the limited capacity for spontaneous cartilage regeneration. Regarding the use of regenerative therapies, it has been reported that one option to restore degenerated cartilage are adipose-derived mesenchymal stem cells (ASCs). The purpose of this review is to describe and compare the efficacy of ASCs versus other therapies in OA. Methods: Recent studies have shown that ASCs exert paracrine effects protecting against degenerative changes in chondrocytes. According to the above, we have carried out a review of the literature using a combination of osteoarthritis, stem cells, and regenerative therapies as keywords. Results: Conventional pharmacological therapies for OA treatment are considered before the surgical option, however, they do not stop the progression of the disease. Moreover, total joint replacement is not recommended for patients under 55 years, and high tibia osteotomy (HTO) is a viable solution to address lower limb malalignment with concomitant OA, but some complications have been described. In recent years, the use of mesenchymal stem cells (MSCs) as a treatment strategy for OA is increasing considerably, thanks to their capacity to improve symptoms together with joint functionality and, therefore, the patients’ quality of life. Conclusions: ASC therapy has a positive effect on patients with OA, although there is limited evidence and little long-term follow-up.