scholarly journals Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review and Meta-Analysis of Prospective Clinical Studies

2021 ◽  
Vol 45 (4) ◽  
pp. 274-283
Author(s):  
Woo Sup Cho ◽  
Sun Gun Chung ◽  
Won Kim ◽  
Chris H. Jo ◽  
Shi-Uk Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Studies ◽  
Large Scale ◽  
Meta Analysis ◽  
Functional Improvement ◽  
Cochrane Library ◽  
Functional Scores ◽  
Meta Regression ◽  
Meta Regression Analysis

Objective To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies.Methods We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose.Results Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed.Conclusion Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.

scholarly journals Mesenchymal Stem Cells: A New Choice for Nonsurgical Treatment of OA? Results from a Bayesian Network Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ziqin Cao ◽  
Yajia Li ◽  
Fuqiang Gao ◽  
Ren Wu ◽  
Pengcheng Dou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pain Relief ◽  
Bayesian Network ◽  
Platelet Rich Plasma ◽  
Meta Analysis ◽  
Joint Disease ◽  
Functional Improvement ◽  
Cochrane Library ◽  
Long Term Treatment

Objective. Osteoarthritis (OA) is the most common degenerative joint disease, causing joint pain, stiffness, and even disability. Guidelines recommend intra-articular injections as an alternative treatment to relieve OA symptoms for patients who demonstrate poor tolerability or compliance to oral administration of drugs. Mesenchymal stem cells (MSCs) are a potential treatment for of OA. We conducted this network meta-analysis to comprehensively compare the efficacy and safety between hyaluronic acid (HA), corticosteroids (GCs), platelet-rich plasma (PRP), and MSCs. Design. Systematic review and Bayesian network meta-analysis. Data Sources. Relevant studies, published from January 2000 to January 2020, in the PubMed, Cochrane library, EMBASE, and CKNI databases. Methods. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement, improvement in joint stiffness, and risk of adverse effects (AEs) were assessed. Results. Twenty-five articles with 4642 patients were included. Overall, MSC therapy was the most effective treatment for pain relief (standardized mean difference compared with placebo = 3.61 , 95% CI [1.87 to 5.35]). Both MSC and PRP therapies improved every symptom of OA effectively and have an advantage over HA and GCs which are recommended by guidelines. MSCs, PRP, HA, and GCs are tolerated well for patients in long-term treatment of OA compared with placebo. Conclusions. The results show that MSCs relieve pain, stiffness, and dysfunction due to OA better than PRP, HA, and GCs and are not statistically correlated with greater safety concerns. More high-quality trials are needed to reconfirm the findings of this study, however, standardization of preparation of MSCs and PRP should be investigated in the future.

scholarly journals Current Evidence of Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review, Meta-analysis, and Meta-regression of Prospective Clinical Studies

2020 ◽  
Author(s):  
Woo Sup Cho ◽  
Sun Gun Chung ◽  
Won Kim ◽  
Chris H. Jo ◽  
Shi-Uk Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Studies ◽  
Meta Analysis ◽  
Mean Difference ◽  
Efficacy And Safety ◽  
Cell Dose ◽  
Human Tendon ◽  
Meta Regression ◽  
Standardized Mean Difference

Abstract Purpose: Although several studies with animals have reported the effects of mesenchymal stem cells (MSCs) for tendon regeneration, little is known about the efficacy and safety of MSCs in human tendon disorders. We performed this meta-analysis to evaluate the efficacy and safety of MSC therapy in patients with tendon disorders enrolled in prospective clinical studies.Methods: We systematically searched prospective clinical studies investigating the effects of MSCs administration on human tendon disorders with at least a 6-month follow-up period on PubMed-Medline, Embase, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. We performed a pairwise meta-analysis using the fixed-effects model to assess treatment response, which was calculated by the standardized mean difference. Meta-regression analyses were performed to assess the relationship between MSCs dose and pooled effect sizes in each cell dose.Results: Four prospective clinical trials investigating the effect of MSCs on tendon disorders were retrieved. MSCs showed significant pooled effect size (overall Hedge’s g pooled standardized mean difference (SMD) = 1.868; 95% confidence interval [CI], 1.274–2.462; P < 0.001). The treatment with MSCs improved all the aspects analyzed, i.e. pain, functional scores, radiologic parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, there was a significant cell dose-dependent response in pain relief (Q = 9.06, P = 0.029). While three studies reported mild adverse events after MSCs injection, these were not severe and relieved spontaneously.Conclusions: Our meta-analysis revealed that MSC therapy may improve pain, function, radiologic, and arthroscopic parameters in patients with tendon disorders. Due to the small number of studies in this meta-analysis and considering the increasing MSCs applications, there is a strong need for large-scale randomized controlled trials to confirm the long-term functional improvement as well as the adverse effects of MSC therapies in tendon disorders.

scholarly journals Current Evidence of Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review, Meta-analysis, and Meta-regression of Prospective Clinical Studies

2020 ◽  
Author(s):  
Woo Sup Cho ◽  
Sun Gun Chung ◽  
Won Kim ◽  
Chris H. Jo ◽  
Shi-Uk Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Studies ◽  
Meta Analysis ◽  
Mean Difference ◽  
Efficacy And Safety ◽  
Cell Dose ◽  
Human Tendon ◽  
Meta Regression ◽  
Standardized Mean Difference

Abstract Purpose Although several studies with animals have reported the effects of mesenchymal stem cells (MSCs) for tendon regeneration, little is known about the efficacy and safety of MSCs in human tendon disorders. We performed this meta-analysis to evaluate the efficacy and safety of MSC therapy in patients with tendon disorders enrolled in prospective clinical studies. Methods We systematically searched prospective clinical studies investigating the effects of MSCs administration on human tendon disorders with at least a 6-month follow-up period on PubMed-Medline, Embase, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. We performed a pairwise meta-analysis using the fixed-effects model to assess treatment response, which was calculated by the standardized mean difference. Meta-regression analyses were performed to assess the relationship between MSCs dose and pooled effect sizes in each cell dose. Results Four prospective clinical trials investigating the effect of MSCs on tendon disorders were retrieved. MSCs showed significant pooled effect size (overall Hedge’s g pooled standardized mean difference (SMD) = 1.868; 95% confidence interval [CI], 1.274–2.462; P < 0.001). The treatment with MSCs improved all the aspects analyzed, i.e. pain, functional scores, radiologic parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, there was a significant cell dose-dependent response in pain relief (Q = 9.06, P = 0.029). While three studies reported mild adverse events after MSCs injection, these were not severe and relieved spontaneously. Conclusions Our meta-analysis revealed that MSC therapy may improve pain, function, radiologic, and arthroscopic parameters in patients with tendon disorders. Due to the small number of studies in this meta-analysis and considering the increasing MSCs applications, there is a strong need for large-scale randomized controlled trials to confirm the long-term functional improvement as well as the adverse effects of MSC therapies in tendon disorders.

scholarly journals Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Random Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

scholarly journals Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis

2020 ◽  
Vol 9 (10) ◽  
pp. 719-728
Author(s):  
Jiaqian Wang ◽  
Liang Zhou ◽  
Yong Zhang ◽  
Lixin Huang ◽  
Qin Shi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Knee Osteoarthritis ◽  
Low Dose ◽  
Meta Analysis ◽  
Cartilage Regeneration ◽  
Cochrane Library ◽  
P Values ◽  
Knee Oa ◽  
Primary Evaluation

Aims The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728.

scholarly journals Correction: Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review and Meta-Analysis of Prospective Clinical Studies

2021 ◽  
Vol 45 (5) ◽  
pp. 410-410
Author(s):  
Woo Sup Cho ◽  
Sun Gun Chung ◽  
Won Kim ◽  
Chris H. Jo ◽  
Shi-Uk Lee ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Studies ◽  
Meta Analysis

scholarly journals The safety and efficacy of mesenchymal stem cells in the treatment of COVID-19-associated pneumonia: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Junwu Wang ◽  
Pengzhi Shi ◽  
Dong Chen ◽  
Shuguang Wang ◽  
Pingchuan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adverse Events ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Serious Adverse Events ◽  
Safe Method ◽  
Radiographic Outcomes ◽  
The Difference

Mesenchymal stem cells (MSCs) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for the relevant studies published between October 2019 and April 2021 in PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. A total of 22 studies involving 371 patients were included in the present study. MSCs were administered in 247 participants, and MSCs were allogeneic from umbilical cord, adipose tissue, menstrual blood, placenta, Wharton's jelly, or unreported sources. Combined results found that MSCs group significantly reduced the incidence of adverse events (OR = 0.43, 95%CI. = 0.22~0.84, P = 0.01) and mortality (OR = 0.17, 95%CI. = 0.06~0.49, P < 0.01), and the difference compared with control group was statistically significant. No MSCs treat-related serious adverse events were reported. The lung function and radiographic outcomes, and biomarker levels of inflammation and immunity all showed improvement trends. Therefore, MSCs therapy is an effective and safe method in the treatment of COVID-19-associated pneumonia and shows advantages in less adverse events and mortality. However, a standard and effective MSCs treatment program needs to be developed.

scholarly journals Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis

2020 ◽  
Vol 28 (12) ◽  
pp. 3827-3842 ◽  
Author(s):  
Emily Claire Doyle ◽  
Nicholas Martin Wragg ◽  
Samantha Louise Wilson
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adverse Effects ◽  
Knee Osteoarthritis ◽  
Large Scale ◽  
Stromal Cell ◽  
Cochrane Library ◽  
Level Of Evidence ◽  
Therapy Strategy

Abstract Purpose This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA). Methods This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of (((“bone marrow-derived mesenchymal stem cell” OR “bone marrow mesenchymal stromal cell” OR “bone marrow stromal cell”)) AND (“osteoarthritis” OR “knee osteoarthritis”)) AND (“human” OR “clinical”))) AND “intra-articular injection” were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases. Results Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve functional outcomes. Subsequently, clinical applications of intra-articular injections of BM-MSCs are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life (QoL); with moderate-to-high level evidence regarding safety for therapeutic administration. However, low confidence in clinical efficacy remains due to a plethora of heterogenous methodologies utilised, resulting in challenging study comparisons. A moderate number of cells (40 × 106) were identified as most likely to achieve optimal responses in individuals with grade ≥ 2 KOA. Likewise, significant improvements were reported when using lower (24 × 106) and higher (100 × 106) cell numbers, although adverse effects including persistent pain and swelling were a consequence. Conclusion Overall, the benefits of intra-articular injections of BM-MSCs were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realise this, long-term large-scale randomised clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies. Level of evidence IV.

Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: A re-examination

2003 ◽  
Vol 183 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Joanna Moncrieff
Keyword(s):  
Large Scale ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Treatment Resistant ◽  
Conventional Antipsychotic ◽  
Conventional Antipsychotics ◽  
Relevant Effect ◽  
Great Heterogeneity ◽  
Meta Regression ◽  
Meta Regression Analysis

BackgroundAlthough there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials.AimsTo re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity.MethodIndividual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity.ResultsTen trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine.ConclusionsIt may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.

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