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Cell Transplantation Jan 2019Spinal cord injury (SCI) is a devastating disease, with a high rate of disability. In this meta-analysis, we aimed to comprehensively assess the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
Spinal cord injury (SCI) is a devastating disease, with a high rate of disability. In this meta-analysis, we aimed to comprehensively assess the efficacy and safety of mesenchymal stem cells (MSCs) in treating clinical SCI patients. We systematically searched the PUBMED, EMBASE, Chinese Biomedical (CBM), Web of Science and Cochrane databases using the strategy of combination of free-text words and MeSH terms. The indicators of the American Spinal Injury Association (ASIA) impairment scale (AIS)-grading improvement rate and adverse effects were displayed with an overall relative risk (RR). For the continuous variables of the ASIA motor score, light-touch score, pinprick score, activities of daily living (ADL) score, and residual urine volume, we used odds ratio (OR) to analyze the data. Eleven studies comprising 499 patients meeting all inclusion and exclusion criteria were included. No serious heterogeneity or publication bias was observed across each study. The results showed that significant improvements of total AIS grade (RR: 3.70; P < 0.001), AIS grade A (RR: 3.57; P < 0.001), ASIA sensory score (OR: 8.63; P < 0.001) and reduction of residual urine volume (OR: -36.37; P = 0.03) were observed in experimental group compared with control group. However, no significant differences of motor score (OR: 1.37, P = 0.19) and ADL score (OR: 2.61, P = 0.27) were observed between experimental and control groups. In addition, there were no serious and permanent adverse effects after cell transplantation. Cell transplantation with MSCs is effective and safe in improving the sensory and bladder functions of SCI patients.
Topics: Cell Transplantation; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Treatment Outcome
PubMed: 30362373
DOI: 10.1177/0963689718808471 -
International Journal of Molecular... Apr 2022Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with... (Meta-Analysis)
Meta-Analysis Review
The Use of Autologous Chondrocyte and Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects in Human Knee Joints-A Systematic Review and Meta-Analysis.
Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with significant functional and socioeconomic consequences. Implants consisting of autologous chondrocytes or mesenchymal stem cells (MSC) seeded onto scaffolds have been suggested as promising therapies to restore these defects. However, the degree of integration between the implant and native cartilage still requires optimization. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, CINAHL) to identify studies that used autologous chondrocyte implants (ACI) or MSC implant therapies to repair chondral defects of the tibiofemoral joint. Data on the integration of the implant-cartilage interface, as well as outcomes of clinical scoring systems, were extracted. Most eligible studies investigated the use of ACI only. Our meta-analysis showed that, across a total of 200 patients, 64% (95% CI (51%, 75%)) achieved complete integration with native cartilage. In addition, a pooled improvement in the mean MOCART integration score was observed during post-operative follow-up (standardized mean difference: 1.16; 95% CI (0.07, 2.24), = 0.04). All studies showed an improvement in the clinical scores. The use of a collagen-based scaffold was associated with better integration and clinical outcomes. This review demonstrated that cell-seeded scaffolds can achieve good quality integration in most patients, which improves over time and is associated with clinical improvements. A greater number of studies comparing these techniques to traditional cartilage repair methods, with more inclusion of MSC-seeded scaffolds, should allow for a standardized approach to cartilage regeneration to develop.
Topics: Cartilage Diseases; Cartilage, Articular; Chondrocytes; Humans; Knee Joint; Mesenchymal Stem Cells; Transplantation, Autologous
PubMed: 35409424
DOI: 10.3390/ijms23074065 -
Cancers Nov 2020Epithelial-to-mesenchymal transition (EMT) is one of the most accepted mechanisms leading to metastasis, which is responsible for most of the cancer-related deaths. In... (Review)
Review
Prognostic Factors Involved in the Epithelial-Mesenchymal Transition Process in Colorectal Cancer Have a Preponderant Role in Oxidative Stress: A Systematic Review and Meta-Analysis.
Epithelial-to-mesenchymal transition (EMT) is one of the most accepted mechanisms leading to metastasis, which is responsible for most of the cancer-related deaths. In order to identify EMT-related biomarkers able to predict clinical outcomes in colorectal cancer (CRC), a systematic review and meta-analysis of prognostic factors associated to overall survival (OS) and progression free survival (PFS) was conducted. The systematic literature search included studies from June 2014 to June 2019 available at PubMed and Scopus databases. Meta-analysis was performed for those markers appearing in minimum three works with a total number of 8656 participants. The rest were enlisted and subjected to functional enrichment. We identified nine clinical biomarkers and 73 EMT-related molecular biomarkers associated to OS and/or PFS in CRC. The significant enrichment of biomarkers found involved in cellular oxidoreductase activity suggests that ROS generation plays an active role in the EMT process. Clinical practice needs new biomarkers with a reliable prognostic value able to predict clinical outcomes in CRC. Our integrative work supports the role of oxidative stress in tumorigenesis and EMT progress highlighting the importance of deciphering this specific mechanism to get a better understanding of metastasis.
PubMed: 33187205
DOI: 10.3390/cancers12113330 -
Discover Oncology Jun 2022Cutaneous squamous cell carcinoma (cSCC) is a disease with globally rising incidence and poor prognosis for patients with advanced or metastatic disease.... (Review)
Review
A tEMTing target? Clinical and experimental evidence for epithelial-mesenchymal transition in the progression of cutaneous squamous cell carcinoma (a scoping systematic review).
Cutaneous squamous cell carcinoma (cSCC) is a disease with globally rising incidence and poor prognosis for patients with advanced or metastatic disease. Epithelial-mesenchymal transition (EMT) is a driver of metastasis in many carcinomas, and cSCC is no exception. We aimed to provide a systematic overview of the clinical and experimental evidence for EMT in cSCC, with critical appraisal of type and quality of the methodology used. We then used this information as rationale for potential drug targets against advanced and metastatic cSCC. All primary literature encompassing clinical and cell-based or xenograft experimental studies reporting on the role of EMT markers or related signalling pathways in the progression of cSCC were considered. A screen of 3443 search results yielded 86 eligible studies comprising 44 experimental studies, 22 clinical studies, and 20 studies integrating both. From the clinical studies a timeline illustrating the alteration of EMT markers and related signalling was evident based on clinical progression of the disease. The experimental studies reveal connections of EMT with a multitude of factors such as genetic disorders, cancer-associated fibroblasts, and matrix remodelling via matrix metalloproteinases and urokinase plasminogen activator. Additionally, EMT was found to be closely tied to environmental factors as well as to stemness in cSCC via NFκB and β-catenin. We conclude that the canonical EGFR, canonical TGF-βR, PI3K/AKT and NFκB signalling are the four signalling pillars that induce EMT in cSCC and could be valuable therapeutic targets. Despite the complexity, EMT markers and pathways are desirable biomarkers and drug targets for the treatment of advanced or metastatic cSCC.
PubMed: 35666359
DOI: 10.1007/s12672-022-00510-4 -
Stem Cell Research & Therapy Apr 2021Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT.
METHODS
Studies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4.
RESULTS
Six randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) - 1.20, p = 0.04; nRCTs: SMD - 0.54, p = 0.04) and platelet engraftment (RCTs: SMD - 0.60, p = 0.04; nRCTs: SMD - 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p < 0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT.
CONCLUSION
MSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.
Topics: Adolescent; Adult; Child; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasm Recurrence, Local
PubMed: 33879242
DOI: 10.1186/s13287-021-02304-x -
Cytotherapy Mar 2022Several studies have shown the efficacy of mesenchymal stem cell (MSC) therapy for lower extremity vascular disease (LEVD) in diabetic patients, but the results are not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AIMS
Several studies have shown the efficacy of mesenchymal stem cell (MSC) therapy for lower extremity vascular disease (LEVD) in diabetic patients, but the results are not consistent. Therefore, the authors conducted a meta-analysis of randomized controlled trials (RCTs) to examine the safety and efficacy of MSC therapy in diabetic patients with LEVD.
METHODS
Eight available databases were searched in both English and Chinese to identify RCTs comparing MSC therapy-based conventional treatment with conventional treatment alone in diabetic patients with LEVD. Three investigators independently screened the literature, extracted the data and assessed the risk bias. Meta-analysis was performed using RevMan 5.4.1 and Stata 14.0.
RESULTS
A total of 10 studies involving 453 patients were included. Compared with conventional treatment only, patients receiving MSC therapy-based conventional treatment had a higher ulcer healing rate, greater number of reduced ulcers and shorter complete healing time. MSC therapy also increased ankle-brachial index and transcutaneous oxygen pressure. In addition, four of the included studies showed that MSC therapy significantly improved the number of new collateral vessels. Moreover, no more adverse events were recorded in the MSC group.
CONCLUSIONS
This meta-analysis suggests that MSC therapy promotes ulcer healing in diabetic LEVD patients with ulcers, improves blood supply and has a favorable safety profile. More large and well-designed RCTs with long-term follow-up are still needed to explore the safety and efficacy of MSC therapy in diabetic patients with LEVD.
Topics: Diabetes Mellitus; Humans; Lower Extremity; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Ulcer; Vascular Diseases
PubMed: 34656420
DOI: 10.1016/j.jcyt.2021.08.001 -
Cytotherapy Jan 2024Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AIMS
Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are unclear.
METHODS
The Web of Science, PubMed, Embase, Cochrane, and Scopus databases were searched from inception to March 28, 2023. Literature screening, data extraction and risk of bias assessment were performed independently by two investigators.
RESULTS
A total of 40 studies were included for data analysis. The findings of our traditional meta-analysis indicate that exosomes derived from stem cells significantly improve the motor function of TSCI at various time points (1 week: weighted mean difference [WMD] = 1.58, 95% confidence interval [CI] 0.87-2.30] 2 weeks: WMD = 3.12, 95% CI 2.64-3.61; 3 weeks: WMD = 4.44, 95% CI 3.27-5.60; 4 weeks: WMD = 4.54, 95% CI 3.42-5.66). Four kinds of stem cell-derived exosomes have been studied: bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and neural stem cells. The results of the network meta-analysis showed that there was no significant statistical difference in the therapeutic effect among the exosomes derived from four kinds of stem cells at different treatment time points. Although exosomes derived from bone marrow mesenchymal stem cells are the current research focus, exosomes derived from neural stem cells have the most therapeutic potential and should become the focus of future attention.
CONCLUSIONS
The exosomes derived from stem cells can significantly improve the motor function of TSCI rats, and the exosomes derived from neural stem cells have the most therapeutic potential. However, the lower evidence quality of animal studies limits the reliability of experimental results, emphasizing the need for more high-quality, direct comparative studies to explore the therapeutic efficacy of exosomes and the best source of stem cells.
Topics: Rats; Animals; Exosomes; Network Meta-Analysis; Reproducibility of Results; Spinal Cord Injuries; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37804282
DOI: 10.1016/j.jcyt.2023.09.002 -
PloS One 2018Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.
METHODS
The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.
RESULTS
Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.
CONCLUSION
MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.
Topics: Acute Lung Injury; Animals; Disease Models, Animal; Evaluation Studies as Topic; Humans; Mesenchymal Stem Cell Transplantation; Paraquat; Pulmonary Edema
PubMed: 29566055
DOI: 10.1371/journal.pone.0194748 -
Archives of Oral Biology Nov 2021To aim of this systematic review was to explore the relationship between Human papillomavirus (HPV) and epithelial-mesenchymal transition (EMT) related to the prognosis... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To aim of this systematic review was to explore the relationship between Human papillomavirus (HPV) and epithelial-mesenchymal transition (EMT) related to the prognosis of oropharyngeal squamous cell carcinoma (OPSCC).
DESIGN
For this systematic review, searches were performed in PubMed, Web of Science, Scopus, Science Direct, and Cochrane, and a random-effects model was used for meta-analysis. The presence of EMT was confirmed by the loss of E-cadherin immunoexpression and overexpression of vimentin.
RESULTS
In summary, EMT-related proteins were expressed regardless of HPV status; however, overall survival was better in HPV-positive OPSCC cases, with a 5.88 times lower death risk compared to HPV-negative patients (OR=0.17; 95%CI=0.10-0.30). Likewise, the maintenance of E-cadherin in OPSCC was associated with an 11.11 times lower risk of death due to the disease (OR=0.09; 95%CI=0.01-0.88).
CONCLUSIONS
More advanced clinical stages (III/IV) and the presence of lymph node metastases (N1-3) were common in OPSCC but were not significantly associated with HPV status.
Topics: Carcinoma, Squamous Cell; Epithelial-Mesenchymal Transition; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 34592489
DOI: 10.1016/j.archoralbio.2021.105267 -
Current Stem Cell Research & Therapy 2023Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease prevalent worldwide with a high mortality rate, and there is currently no specific medicine to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease prevalent worldwide with a high mortality rate, and there is currently no specific medicine to treat patients.
OBJECTIVE
We aimed to assess the safety and efficacy of stem cell therapy for COVID-19 by providing references for subsequent clinical treatments and trials.
METHOD
We systematically searched PubMed, Embase, Cochrane, and Web of Science, using the following keywords: "stem cell" or "stromal cell" and "COVID-19." Controlled clinical trials published in English until 24th August 2021 were included. We followed the PRISMA guidelines and used Cochrane Collaboration's tool for assessing the risk of bias. We analysed the data using a fixed-effect model.
RESULTS
We identified 1779 studies, out of which eight were eligible and included in this study. Eight relevant studies consisted of 156 patients treated with stem cells and 144 controls (300 individuals in total). There were no SAEs associated with stem cell therapy in all six studies, and no significant differences in AEs (p = 0.09, I = 40%, OR = 0.53, 95% CI: 0.26 to 1.09) between the experimental group and control group were observed. Moreover, the meta-analysis found that stem cell therapy effectively reduced the high mortality rate of COVID-19 (14/156 vs. 43/144; p<0.0001, I2 = 0%, OR=0.18, 95% CI: 0.08 to 0.41).
CONCLUSION
This study suggests that MSCs therapy for COVID-19 has shown some promising results in safety and efficacy. It effectively reduces the high mortality rate of COVID-19 and does not increase the incidence of adverse events.
Topics: Humans; COVID-19; Mesenchymal Stem Cells; Stromal Cells; Stem Cell Transplantation
PubMed: 34872483
DOI: 10.2174/1574888X16666211206145839