Dataset Information

Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Mesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA.

Methods

Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and CNKI (National Knowledge Infrastructure, China) databases were systematically reviewed. The pain level and function improvements were evaluated using visual analog scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC). The pooled estimate was calculated with weighted mean difference (WMD) with 95% confidence intervals (95%CIs).

Results

Nine RCTs involving 476 patients were included in this meta-analysis. The pooled estimate showed that the treatment of MSCs significantly reduced VAS, WOMAC pain, WOMAC stiffness, and WOMAC function scores at a long-term follow-up (12 or 24?months). However, for the IKDC and WOMAC total scores, MSCs also showed significant improvement in these outcomes, although this was not statistically significant when compared to the control.

Conclusion

Based on the current studies, our results suggested that MSCs were a promising option for the treatment of patients with knee OA. However, considering the potential limitations, more well-performed, large-scale RCTs are needed to verify our findings.

SUBMITTER: Qu H

PROVIDER: S-EPMC7789676 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials.

Qu Huazheng H Sun Shui S

Journal of orthopaedic surgery and research 20210106 1

<h4>Background</h4>Mesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA.<h4>Methods</h4>Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, Chin ...[more]

PMID: 33407686

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Project description:BackgroundThe management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis.MethodsWe conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations.ResultsFour trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: - 0.58; 95% CI - 0.98, - 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low).ConclusionsOur findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings.

Project description:Traditional Chinese medication (TCM) has analgesic and anti-inflammatory effects in patients with knee osteoarthritis (OA). We conducted the first systematic review of the best quantitative and qualitative evidence currently available in order to evaluate the effectiveness of TCM in relieving pain in knee OA. A comprehensive literature search was conducted using three English and four Chinese biomedical databases from their inception through March 1, 2015. We included randomized controlled trials of TCM for knee OA with intervention durations of at least two weeks. The effects of TCM on pain and other clinical symptoms were measured with the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The total effectiveness rate, which was used to assess overall pain, physical performance and wellness, was also measured. Two researchers independently extracted data on study design, population characteristics, duration, intervention, outcomes, risk of bias, and primary results. We performed a random-effects meta-analysis when appropriate. We also explored factors that could explain the heterogeneity by conducting subgroup and meta-regression analyses. Twenty-three studies, totaling 2362 subjects, met the eligibility criteria. Treatments were formulated with an average of 8 Chinese herbs and were prescribed based on the traditional Chinese diagnostic method of syndrome differentiation. The mean treatment duration was seven weeks, with oral administration occurring one to three times a day. Compared with non-steroidal anti-inflammatory drugs and intra-articular hyaluronate injections, 18 of the studies showed significantly improved VAS pain scores (Mean Difference [MD] [Formula: see text] 0.56; 95% confidence interval [CI], 0.18 to 0.94; [Formula: see text]), six of the studies showed significantly improved WOMAC pain subscale scores (MD [Formula: see text] 2.23; 95% CI, 0.56 to 3.91; [Formula: see text]), and 16 of the trials showed significantly improved total effectiveness rates (risk ratio [Formula: see text] 1.12; 95% CI, 1.05 to 1.19; [Formula: see text] 0.0003). In addition, TCM showed a lower risk of adverse events than standard western treatments. This evidence suggests that TCM is safe and effective for improving pain, function, and wellness in treatments of knee OA. However, there is inherent clinical heterogeneity (diverse TCM formulations, controls, and treatment regimens) among the included trials. Despite these limitations, the potential analgesic effects of TCM warrant further methodologically rigorous research to determine the clinical implications of TCM on pain management in knee OA.

Project description:Study designMeta-analysis.ObjectivesWe aim to identify the clinically significant ideal Mesenchymal Stem Cell (MSC) count in the management of osteoarthritis of knee from Randomized Controlled Trials (RCTs) available in the literature.Materials and methodsWe conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till August 2021 for RCTs conducted in the management of knee osteoarthritis using MSC therapy specifying the quantity of MSCs delivered. We categorized the studies based on the MSC count utilized in them into four groups namely <1 × 107 MSCs (Group I), 1-5x107 MSCs (Group II), 5-10 × 107 MSCs (Group III), and >10 × 107 MSCs (Group IV). Visual Analog Score (VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software.Results14 studies involving 564 patients were included for analysis. We noted incremental decrease in the VAS with increasing dosage of MSCs at 12 months [Group I,WMD = 2.641(p = 0.854); Group II, WMD = -4.853(p = 0.379); Group III, WMD = -12.154 (p = 0.316); Group IV, WMD = -15.935(p = 0.116)], and 24 months [Group I,WMD = -6(p = 0.001); Group II, WMD = -15(p = 0.001); Group IV, WMD = -20(p = 0.001)]. We also noted incremental improvement in the WOMAC, KOOS with increasing dosage of MSCs at 12 months [Group I, WMD = 7(p = 0.001); Group II, WMD = 28(p = 0.001); Group IV, WMD = 30(p = 0.001)] and [Group II, WMD = -2.562(p = 0.676); Group III, WMD = 7.670(p = 0.099); Group IV, WMD = 13.475(p = 0.261)] respectively. However, we noted significant reduction in the Lysholm score in Group IV, compared to the others at 12 months (WMD = -12.5, 95%CI[-25.883,0.883]) and 24 months (WMD = -6.6, 95%CI[-23.596,10.396]). We did not find any significant increase in the adverse events with incremental dosage of MSCs in any of the groups compared.ConclusionCompared to the four dosage groups of MSCs analyzed, Group III showed consistent significant improvement in pain and functional outcomes analyzed compared to the other groups. Hence, we recommend a cell volume of 5-10 × 107 cells to be delivered to the target site to obtain superior benefits out of the procedure. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the ideal count of MSCs to be delivered in the cellular therapy for knee osteoarthritis.

Project description:Study Design: Meta-analysis. Objectives: We aimed to analyze the impact of cultured expansion of autologous mesenchymal stromal cells (MSCs) in the management of osteoarthritis of the knee from randomized controlled trials (RCTs) available in the literature. Materials and Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library until August 2021 for RCTs analyzing the efficacy and safety of culture-expanded compared to non-cultured autologous MSCs in the management of knee osteoarthritis. The Visual Analog Score (VAS) for pain, Western Ontario McMaster University's Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the analyzed outcomes. Analysis was performed in R-platform using OpenMeta [Analyst] software. Results: Overall, 17 studies involving 767 patients were included for analysis. None of the studies made a direct comparison of the culture expanded and non-cultured MSCs, hence we pooled the results of all the included studies of non-cultured and cultured types of MSC sources and made a comparative analysis of the outcomes. At six months, culture expanded MSCs showed significantly better improvement (p < 0.001) in VAS outcome. Uncultured MSCs, on the other hand, demonstrated significant VAS improvement in the long term (12 months) in VAS (p < 0.001), WOMAC (p = 0.025), KOOS score (p = 0.016) where cultured-expanded MSCs failed to demonstrate a significant change. Culturing of MSCs did not significantly increase the complications noted (p = 0.485). On sub-group analysis, adipose-derived uncultured MSCs outperformed culture-expanded MSCs at both short term (six months) and long term (12 months) in functional outcome parameters such as WOMAC (p < 0.001, p = 0.025), Lysholm (p < 0.006), and KOOS (p < 0.003) scores, respectively, compared to their controls. Conclusions: We identified a void in literature evaluating the impact of culture expansion of MSCs for use in knee osteoarthritis. Our indirect analysis of literature showed that culture expansion of autologous MSCs is not a necessary factor to obtain superior results in the management of knee osteoarthritis. Moreover, while using uncultured autologous MSCs, we recommend MSCs of adipose origin to obtain superior functional outcomes. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the need for culture expansion of MSCs for use in cellular therapy of knee osteoarthritis.

Project description:INTRODUCTION:There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. METHODS:We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. RESULTS:The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2?=?94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2?=?95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I2?=?75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2?=?53%, p?=?0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2?=?20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2?=?0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS?=?0.93; LI: rS?=?0.86; p?<?0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. CONCLUSION:This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

Project description:Background: There is increased interest in proprioceptive training for knee osteoarthritis (KOA). However, little consensus supports the effectiveness of this intervention. Objective: This meta-analysis aimed to assess the effects of proprioceptive training on symptoms, function, and proprioception in people with KOA. Methods: The PubMed, Cochrane Library, Web of Science, and EMBASE databases were systematically searched from the inception dates to April 16, 2021 for relevant randomized controlled trials (RCTs). Data were pooled by calculating the standardized mean differences (SMDs) and 95% confidence intervals (CIs). A random-effects model was used for the analyses. Results: A total of 24 RCTs involving 1,275 participants were included in our analysis. This study indicated that compared to no intervention, proprioceptive training significantly improved pain, stiffness, physical function, joint position sense (JPS), muscle strength, mobility, and knee ROM (P < 0.05) in people with KOA. When compared to other non-proprioceptive training, proprioceptive training provided better results in terms of JPS (SMD = -1.28, 95%CI: [-1.64, -0.92], I 2 = 0%, P < 0.00001) and mobility (timed walk over spongy surface) (SMD = -0.76, 95%CI: [-1.33, -0.18], I 2 = 64%, P = 0.01), and other results are similar. When proprioceptive training plus other non-proprioceptive training compared to other non-proprioceptive training, the two groups showed similar outcomes, but there was a greater improvement for JPS (SMD = -1.54, 95%CI: [-2.74, -0.34], I 2 = 79%, P = 0.01), physical function (SMD = -0.34, 95%CI: [-0.56, -0.12], I 2 = 0%, P = 0.003), and knee ROM (P < 0.05) in the proprioceptive training plus other non-proprioceptive training group. When proprioceptive training plus conventional physiotherapy compared against conventional physiotherapy, the two groups demonstrated similar outcomes, but there was a significant improvement for JPS (SMD = -0.95, 95%CI: [-1.73, -0.18], I 2 = 78%, P = 0.02) in the proprioceptive training plus conventional physiotherapy group. Conclusions: Proprioceptive training is safe and effective in treating KOA. There is some evidence that proprioceptive training combined with general non-proprioceptive training or conventional physiotherapy appears to be more effective and should be considered as part of the rehabilitation program. However, given that the majority of current studies investigated the short-term effect of these proprioceptive training programs, more large-scale and well-designed studies with long-term follow up are needed to determine the long-term effects of these proprioceptive training regimes in KOA. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, PROSPERO, identifier: CRD42021240587.

Project description:ObjectiveThis systematic review and meta-analysis were performed to investigate the efficacy and safety of Chinese herbal medicine (CHM) in the treatment of knee osteoarthritis (KOA).MethodsAn electronic search was conducted in eight databases (PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese VIP Database, and Wanfang Database) from inception until December 2019. The risk of bias assessment of the included RCTs was evaluated by Cochrane collaboration's tool. The inclusion criteria were RCTs that investigated the efficacy and safety of CHM in the treatment of KOA, with no restrictions on publication status or language. The exclusion criteria included nonrandomized or quasi-RCTs, no clear KOA diagnostic approach, combined Chinese medicinal herbs with other traditional Chinese medicine treatment modalities, and published using repeated data and missing data. We computed the relative risk (RR) and the standard mean difference (SMD) for dichotomous outcomes and continuous outcomes, respectively. When heterogeneity was detected or there was significant statistical heterogeneity (P < 0.05 or I 2 > 50%), a random-effects model was employed, followed by further subgroup analysis and metaregression estimations to ascertain the origins of heterogeneity. Otherwise, we used a fixed-effects model (P ≥ 0.05 or I 2 ≤ 50%). The primary outcome measures were visual analog score (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, and Lequesne index. Secondary outcome measures were the total clinical effective rate and adverse events. The meta-analysis was performed using the Stata 14.0 software.ResultsA total of 56 RCTs comprising 5350 patients met the inclusion criteria. This meta-analysis showed that application of CHM as adjuvant therapy or monotherapy for KOA can significantly decrease VAS, WOMAC, and the Lequesne index and improve the Lysholm score as well as the total effective rate. In addition, this treatment has fewer adverse effects, suggesting that CHM is generally safe and well tolerated among patients with KOA.ConclusionOur study offers supportive evidence that CHM, either adjuvant therapy or monotherapy, reduces the VAS, WOMAC, and Lequesne index and improves the Lysholm score and overall effective rate in patients with KOA. Additionally, CHM was well tolerated and safe in KOA patients. We found frequently used CHMs that might contribute to the formulation of a herbal formula that could be considered for further clinical use. However, given the heterogeneity and limited sample size in this study, larger multicenter and high-quality RCTs are needed to validate the benefits of CHM in the treatment of KOA.

Dataset Information

Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials.

Background

Methods

Results

Conclusion

Publications

Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials.

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