Intraarticular injection of allogenic chondroprogenitors for treatment of osteoarthritis in rabbit knee model.
Ontology highlight
ABSTRACT:
SUBMITTER: Vinod E
PROVIDER: S-EPMC6349637 | biostudies-literature | 2019 Jan-Feb
REPOSITORIES: biostudies-literature
Publications
Intraarticular injection of allogenic chondroprogenitors for treatment of osteoarthritis in rabbit knee model.
Vinod Elizabeth E James Jithu Varghese JV Sabareeswaran Arumugam A Amirtham Soosai Manickam SM Thomas George G Sathishkumar Solomon S Ozbey Ozlem O Boopalan P R J V C PRJVC
Journal of clinical orthopaedics and trauma 20180711 1
Similar Datasets
Project description:Osteoarthritis (OA) impacts millions of people and places a high burden on healthcare systems in the United States. Current treatment modalities have limitations and do not address underlying pathology. Lately, there has been an immense growth in the use of biologics, including perinatal allogenic tissues for orthopedic regenerative medicine applications. Amniotic tissue is an exciting new alternative for such applications. Despite several published studies that reported its use for treatment of ophthalmic conditions and complex wounds, there are limited clinical studies evaluating its safety and efficacy in treating patients suffering with knee or hip OA. In this manuscript, I focused on three prospective clinical studies which evaluated the safety and efficacy of amniotic tissue in patients suffering with moderate knee or hip OA. The results from these studies presented the scientific community with much needed, well-executed, and prospective clinical trials. Though these trials demonstrated that administration of amniotic tissue in knee or hip joint is safe and potentially effective, more multi-center, prospective, double-blinded, randomized controlled trials are warranted to further establish the efficacy of amniotic tissue to mitigate symptoms of knee and hip OA to ultimately justify its clinical use.
| S-EPMC9031613 | biostudies-literature
Project description:ObjectiveOsteoarthritis (OA) is a degenerative disease that causes serious damage to joints, especially in elderly patients. The aim of study was to demonstrate the effectiveness of intraarticular therapies that are currently used or recently popularized in the treatment of OA.DesignThe baseline values were determined by walking the rats on the CatWalk system. Afterwards, a monosodium iodoacetate (MIA)-induced knee OA model was created with intraarticular MIA, and the rats were walked again on the CatWalk system and post-OA values were recorded. At this stage, the rats were divided into 4 groups, and intraarticular astaxanthin, intraarticular corticosteroid, intraarticular hyaluronic acid, and intraarticular astaxanthin + hyaluronic acid were applied to the groups, respectively. The rats were walked once more and posttreatment values were obtained. Nine different dynamic gait parameters were used in the comparison.ResultsSignificant changes were measured in 6 of the 9 dynamic gait parameters after the MIA-induced knee OA model. While the best improvement was observed in run duration (P = 0.0022), stride length (P < 0.0001), and swing speed (P = 0.0355) in the astaxanthin group, the results closest to basal values in paw print length (P < 0.0001), paw print width (P = 0.0101), and paw print area (P = 0.0277) were seen in the astaxanthin + hyaluronic acid group.ConclusionAstaxanthin gave better outcomes than corticosteroid and hyaluronic acid in both dynamic gait parameters and histological examinations. Intraarticular astaxanthin therapy can be a good alternative to corticosteroid and hyaluronic acid currently used in intraarticular therapy to treat OA.
| S-EPMC8804824 | biostudies-literature
Project description:BackgroundAnimal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. However, these methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA.MethodsOur studies attempted to find a rapid, easy, and consistent with the natural pathological process of OA modeling method by intra-articular injection of stromal cell-derived factor 1 (SDF-1) in the rabbit knee. After induction we collected cartilage specimens from the medial femoral condyle to undergo macroscopic, histological, immunohistochemical, and biochemical evaluations. Meanwhile, compared with Hulth surgical method to evaluate its efficacy.ResultsMacroscopic observation and modified Mankin score of histological staining exhibited typical features of middle stage OA cartilage in SDF-1 injected groups. Immunohistochemically, the positive expression of interleukin-1 (IL-1) and tumor necrosis factor α(TNF-α) was earlier and higher in high dose SDF-1 group than the surgical group. The matrix metalloproteinases (MMPs) in synovial fluid and chondrocytes significantly increased, but type II collagen (COLII) and aggrecan (ACAN) protein expressions decreased in SDF-1 injected group following the extension of time and increase of SDF-1 concentration.ConclusionsOur data indicated intra-articular injection of SDF-1 (40μg/kg, three times for 12 weeks) can induce rabbit knee OA model successfully more rapidly and easily than traditional surgical modeling. The study provided a further option for the establishment of knee OA animal model.
| S-EPMC8019508 | biostudies-literature
Project description:In recent years, mesenchymal stromal cells (MSCs) have shown promise as a therapy in treating musculoskeletal diseases, and it is currently believed that their therapeutic effect is mainly related to the release of proteins and extracellular vesicles (EVs), known as secretome. In this work, three batches of canine MSC-secretome were prepared by standardized processes according to the current standard ISO9001 and formulated as a freeze-dried powder named Lyosecretome. The final products were characterized in protein and lipid content, EV size distribution and tested to ensure the microbiological safety required for intraarticular injection. Lyosecretome induced the proliferation of adipose tissue-derived canine MSCs, tenocytes, and chondrocytes in a dose-dependent manner and showed anti-elastase activity, reaching 85% of inhibitory activity at a 20 mg/mL concentration. Finally, to evaluate the safety of the preparation, three patients affected by bilateral knee or elbow osteoarthritis were treated with two intra-articular injections (t = 0 and t = 40 days) of the allogeneic Lyosecretome (20 mg corresponding 2 × 106 cell equivalents) resuspended in hyaluronic acid in one joint and placebo (mannitol resuspended in hyaluronic acid) in the other joint. To establish the safety of the treatment, the follow-up included a questionnaire addressed to the owner and orthopaedic examinations to assess lameness grade, pain score, functional disability score and range of motion up to day 80 post-treatment. Overall, the collected data suggest that intra-articular injection of allogeneic Lyosecretome is safe and does not induce a clinically significant local or systemic adverse response.
| S-EPMC8614457 | biostudies-literature
Project description:BackgroundThe 2013 American Academy of Orthopaedic Surgeons (AAOS) guidelines made strong recommendations against intraarticular hyaluronic acid (IAHA) for patients with knee osteoarthritis (OA), as evidence supporting improvements in pain did not meet the minimal clinically important improvement (MCII) threshold. However, there may be important distinctions based on IAHA molecular weight (MW). Hence our objective was to evaluate the efficacy of IAHAs in knee OA based on molecular weight.MethodsRandomized controlled trials were searched within MEDLINE, Embase, and CENTRAL and selected based on AAOS criteria. A pain measure hierarchy and longest follow-up were used to select one effect size from each trial. Mean differences between interventions were converted to standardized mean differences (SMDs) and incorporated into a random-effects Bayesian network meta-analysis. High MW (HMW) was defined as ≥6000 kDa, and low MW (LMW) as < 750 kDa.ResultsHMW IAHA was associated with a statistically significant and possibly clinically significant improvement in pain (SMD - 0.57 (95% credible interval [Crl]: - 1.04, - 0.11), exceeding the - 0.50 MCII threshold. LMW IAHA had a lesser, non-significant improvement (- 0.23, 95% Crl: - 0.67, 0.20). Back-transforming SMDs to the WOMAC pain scale indicated a 14.65 (95% CI: 13.93, 15.62) point improvement over IA placebo, substantially better than the 8.3 AAOS MCII threshold.ConclusionsUnlike LMW IAHA, HMW IAHA exceeded the MCII threshold for pain relief, suggesting that improvements can be subjectively perceived by the treated patient. Amalgamation of LMW and HMW may have blurred the benefits of IAHA in the past, leading to negative recommendations. Differentiation according to MW offers refined insight for treatment with IAHA.
| S-EPMC7585216 | biostudies-literature
Project description:Lumbar facet joint (LFJ) osteoarthritis (OA) is an important etiology of low back pain. Several animal models of LFJ OA have been established using intraarticular injection of various chemicals. This study aimed to establish a rat model of LFJ OA using urinary plasminogen activator (uPA). Sprague-Dawley rats were treated with intraarticular injection in the L5-L6 facet joints with uPA (OA group, n = 40) or normal saline (vehicle group, n = 40). Mechanical and thermal hyperalgesia in the ipsilateral hind paws were evaluated using von Frey hairs and a thermoalgesia instrument, respectively. Toluidine blue staining, hematoxylin-eosin staining, and immunohistochemical examination of the LFJ was performed. Treatment with uPA induced cartilage damage, synovitis, and proliferation of synovial cells in the fact joints. The OA group showed significantly higher hyperalgesia in the hind paws in comparison with the vehicle group and normal controls (P < 0.05). Expression of IL-1β, TNF-α, and iNOS in the LFJ cartilage in the OA group was significantly increased (P < 0.05). A rat model of LFJ OA was successfully established using intraarticular injection of uPA. This animal model is convenient and shows good resemblance to human OA pathology.
| S-EPMC4402705 | biostudies-other
Project description:OBJECTIVE:FX006 is a novel, microsphere-based, extended-release formulation of triamcinolone acetonide for intraarticular (IA) injection designed to maintain treatment concentration in the joint and provide prolonged analgesic benefits in patients with osteoarthritis (OA) of the knee. This study was undertaken to compare the analgesic benefits of 2 FX006 doses with saline placebo injection. METHODS:In this phase IIb study, participants with knee OA (Kellgren/Lawrence grade 2-3) and average daily pain (ADP) intensity ≥5 to ≤9 (on a 0-10 Numerical Rating Scale) were randomized (1:1:1) to receive single IA injections of FX006 32 mg (n = 104) or 16 mg (n = 102) or saline placebo (n = 100). The primary end point was the least squares mean (LSM) change from baseline to week 12 in weekly mean ADP intensity scores for FX006 32 mg versus saline placebo. RESULTS:The primary end point was not met (LSM change at week 12 -3.1 with FX006 32 mg versus -2.5 with saline placebo; LSM difference [95% confidence interval] -0.58 [-1.22, 0.07]) (P = 0.08). However, improvements in ADP intensity were significantly greater with FX006 32 mg than saline placebo at weeks 1-11 and week 13. Improvements in ADP intensity were significantly greater with FX006 16 mg versus saline placebo at weeks 1-9. A dose-response effect in duration of maximal analgesic effect was evident (13 weeks with 32 mg versus 9 weeks with 16 mg), with FX006 32 mg providing increased therapeutic benefit relative to FX006 16 mg. All treatments were well tolerated. CONCLUSION:Although the primary end point was not met, our findings indicate a prolonged reduction in symptoms with FX006 with an evident dose response and a safety profile similar to saline placebo.
| S-EPMC5814922 | biostudies-literature
Project description:ObjectiveTo determine whether clinical correlates of knee osteoarthritis (OA) affect the outcome of intraarticular steroid injections (IASI) in symptomatic knee OA.MethodsMen and women aged ≥ 40 years with painful knee OA who participated in an open-label trial of IASI completed questionnaires and clinical examination. The Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) criteria were used to assess response to therapy in the short term (within 2 weeks). Among those who initially responded, those whose pain had not returned to within 20% of the baseline Knee Injury and Osteoarthritis Outcome Score pain score at 6 months were characterized as longer-term responders. Log-binomial regression was used to examine factors associated with outcome.ResultsOne hundred ninety-nine participants were included, of whom 146 (73.4%) were short-term and 40 (20.1%) longer-term responders. Compared to short-term nonresponders, participants with these characteristics were more likely to be short-term responders: medial joint line tenderness [relative risk (RR) 1.42, 95% CI 1.10-1.82], medial and lateral joint line tenderness (RR 1.38, 95% CI 1.03-1.84), patellofemoral tenderness (RR 1.27, 95% CI 1.04-1.55), anserine tenderness (RR 1.27, 95% CI 1.06-1.52), and a belief that treatment would be effective [RR/unit increase (range 0-10) = 1.05 (1.01-1.09)]. Aspiration of joint fluid (RR 0.79, 95% CI 0.66-0.95) and previous ligament/meniscus injury (RR 0.63, 95% CI 0.44-0.91) were associated with a reduced risk of being a short-term responder. Compared to initial nonresponders and those whose pain recurred within 6 months, participants with a higher number of pain sites [RR/unit increase (range 0-10) = 0.83, 95% CI 0.72-0.97], chronic widespread pain (RR 0.32, 95% CI 0.10-0.98), perceived chronicity of disease [RR/unit increase (range 0-10) = 0.86, 95% CI 0.78-0.94], and a higher depression score [RR/unit increase (range 0-21) = 0.89, 95% CI 0.81-0.99] were less likely to be longer-term responders.ConclusionAmong patients with symptomatic knee OA, tenderness around the knee was associated with better short-term outcome of IASI. However, clinical-related factors did not predict longer-term response, while those with chronic widespread pain and depressive symptoms were less likely to obtain longer-term benefits.
| S-EPMC10563584 | biostudies-literature
Project description:ObjectiveWe examined the longterm effectiveness of corticosteroid or hyaluronic acid injections in relieving symptoms among persons with knee osteoarthritis (OA).MethodsUsing Osteoarthritis Initiative data, a new-user design was applied to identify participants initiating corticosteroid or hyaluronic acid injections (n = 412). Knee symptoms (pain, stiffness, function) were measured using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We used marginal structural models adjusting for time-varying confounders to estimate the effect on symptoms of newly initiated injection use compared to nonusers over 2 years of followup.ResultsAmong 412 participants initiating injections, 77.2% used corticosteroid injections and 22.8% used hyaluronic acid injections. About 18.9% had additional injection use after initiation, but switching between injection types was common. Compared to nonusers, on average, participants initiating a corticosteroid injection experienced a worsening of pain (yearly worsening: 1.24 points, 95% CI 0.82-1.66), stiffness (yearly worsening: 0.30 points, 95% CI 0.10-0.49), and physical functioning (yearly worsening: 2.62 points, 95% CI 0.94-4.29) after adjusting for potential confounders with marginal structural models. Participants initiating hyaluronic acid injections did not show improvements of WOMAC subscales (pain: 0.50, 95% CI -0.11 to 1.11; stiffness: -0.07, 95% CI -0.38 to 0.24; and functioning: 0.49, 95% CI -1.34 to 2.32).ConclusionAlthough intraarticular injections may support the effectiveness of reducing symptoms in short-term clinical trials, the initiation of corticosteroid or hyaluronic acid injections did not appear to provide sustained symptom relief over 2 years of followup for persons with knee OA.
| S-EPMC6119626 | biostudies-literature
Project description:ObjectiveThis literature review summarizes evidence on the safety and efficacy of intraarticular hyaluronic acid (IAHA) preparations approved in the United States for the treatment of osteoarthritis of the knee.DesignA systematic literature search was performed in PubMed, Ovid MEDLINE, and SCOPUS databases. Only studies in which clinical outcomes of individual IAHA preparations alone could be assessed when compared to placebo, no treatment, other standard knee osteoarthritis treatments, and IAHA head-to-head studies were selected.ResultsOne hundred nine articles meeting our inclusion criteria were identified, including 59 randomized and 50 observational studies. Hylan G-F 20 has been the most extensively studied preparation, with consistent results confirming efficacy in placebo-controlled studies. Efficacy is also consistently reported for Supartz, Monovisc, and Euflexxa, but not for Hyalgan, Orthovisc, and Durolane. In the head-to-head trials, high-molecular-weight (MW) Hylan G-F 20 was consistently superior to low MW sodium hyaluronate preparations (Hyalgan, Supartz) up to 20 weeks, whereas one study reported that Durolane was noninferior to Supartz. Head-to-head trials comparing high versus medium MW preparations all used Hylan G-F 20 as the high MW preparation. Of the IAHA preparations with strong evidence of efficacy in placebo-controlled studies, Euflexxa was found to be noninferior to Hylan G-F 20. There are no direct comparisons to Monovisc. One additional IAHA preparation (ie, Synovial), which has not been assessed in placebo-controlled studies, was also noninferior to Hylan G-F 20.ConclusionIAHA efficacy varies widely across preparations. High-quality studies are required to assess and compare the safety and efficacy of IAHA preparations.
| S-EPMC8808930 | biostudies-literature