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Breast Cancer Research and Treatment Oct 2020Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC.
METHODS
A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS).
RESULTS
Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006).
CONCLUSION
High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.
Topics: Breast Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; Lymphatic Metastasis; Prognosis; Triple Negative Breast Neoplasms
PubMed: 32710280
DOI: 10.1007/s10549-020-05810-3 -
Regenerative Therapy Dec 2024Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs.... (Review)
Review
Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs. They can be caused by ischemic factors or hemorrhages, with ischemic strokes being the most common among the population. Therapies for patients suffering from this condition are limited and primarily focus on acute-phase treatment. In recent years, there has been an increase in cellular therapies, employing Stem Cells to mitigate or eliminate the consequences arising from this disease. Mesenchymal Stem Cells (MSCs) hold substantial therapeutic potential in Nervous System pathologies due to their low antigenicity and capacity to differentiate into various human tissues, such as adipogenic, chondrogenic, and osteogenic tissues. This study conducts a literature review using the "clinical trials" and "Pubmed" database, summarizing all ongoing clinical trials for ischemic strokes that utilize MSCs as treatment.
PubMed: 38633415
DOI: 10.1016/j.reth.2024.03.026 -
Stem Cell Research & Therapy Mar 2015The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy.
METHODS
We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger's tests.
RESULTS
Twenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1-5)×10(6) was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with administration syngeneic bone marrow-derived MSCs intravenously at cell dose of 5×10(6) at 2 months after TBI, using sevofluorane as anesthetic agent.
CONCLUSIONS
We conclude that MSCs therapy may improve locomotor recovery after TBI. However, additional well-designed and well-reported animal studies are needed to guide further clinical studies.
Topics: Animals; Brain Injuries; Cell- and Tissue-Based Therapy; Disease Models, Animal; Female; Locomotion; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Motor Activity; Rats; Rats, Sprague-Dawley; Rats, Wistar; Recovery of Function
PubMed: 25881229
DOI: 10.1186/s13287-015-0034-0 -
Avicenna Journal of Medical... 2022Menstrual-derived Stem Cells (MenSC) are a potential novel source of mesenchymal stem cells. There is an increased interest in investigating the therapeutic potential of... (Review)
Review
Menstrual-derived Stem Cells (MenSC) are a potential novel source of mesenchymal stem cells. There is an increased interest in investigating the therapeutic potential of MenSC due to the various advantages they exhibit, when compared to other types of stem cells. MenSC are obtained non-invasively from menstrual blood. Thus, collection of MenSC is simple, reproducible and can be carried out periodically, with minimal complications. MenSC are present in abundance, are highly proliferative, exhibit a low immunogenicity and lack ethical issues. MenSC have shown the ability to differentiate into several lineages. The therapeutic potential of MenSC in non-gynaecological applications has been investigated in wound healing, neurological, musculo-skeletal, cardiovascular, respiratory, and liver disorders, as well as in diabetes and cancer. Human clinical trials are limited. To date, therapeutic efficacy and safety have been reported in patients with Avian influenza A subtype H7N9, COVID-19, congestive heart failure, multiple sclerosis and Duchene muscular dystrophy. However, further clinical trials in humans should be conducted, to study the long-term therapeutic effects of these stem cells in various diseases and to further explore their mechanism of action. This systematic review focuses on the application of MenSC in non-gynaecological diseases.
PubMed: 35509365
DOI: 10.18502/ajmb.v14i1.8166 -
Journal of Clinical Medicine Jun 2023The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the... (Review)
Review
BACKGROUND
The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach.
METHODS
We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction.
RESULTS
Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 10-1 × 10 mesenchymal stem cells, averaging 2.26 × 10. Most BMP-transduced MSC studies used lentivirus.
CONCLUSIONS
This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study.
PubMed: 37373757
DOI: 10.3390/jcm12124064 -
Cureus Dec 2022Bronchopulmonary dysplasia (BPD) is a frequent sequela of modern medicine when infants are born prematurely. Currently, there is no single treatment or combination of... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a frequent sequela of modern medicine when infants are born prematurely. Currently, there is no single treatment or combination of treatments to prevent or fully treat BPD. Mesenchymal stem cells (MSCs) have promising properties that could aid in the reversal of lung injury, as seen in patients with BPD. This study reviews the available evidence regarding the safety and efficacy of the use of MSCs for the treatment of evolving and established BPD. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We found eight studies that fulfilled the inclusion and exclusion criteria. While all studies proved the safety and efficacy of MSCs administered intravenously and intratracheally, the only available randomized controlled trial (RCT) failed to demonstrate the benefit of MSC administration in the early treatment of BPD. The remaining studies varied between phase I clinical trials and case reports, but all seemed to show some evidence that MSCs may be of benefit in the late treatment of established BPD. Considering some of the studies have less evidence, early treatment to prevent lung fibrosis may be more successful, particularly in the younger gestational ages where lung development is more immature, and research should focus on this.
PubMed: 36660501
DOI: 10.7759/cureus.32598 -
Pharmaceuticals (Basel, Switzerland) Oct 2021Musculoskeletal ailments affect millions of people around the world and place a high burden on healthcare. Traditional treatment modalities are limited and do not... (Review)
Review
Musculoskeletal ailments affect millions of people around the world and place a high burden on healthcare. Traditional treatment modalities are limited and do not address underlying pathologies. Mesenchymal stem cells (MSCs) have emerged as an exciting therapeutic alternative and Wharton's jelly-derived mesenchymal stem cells (WJSCs) are some of these. This review reports the clinical and functional outcomes of the applications of WJSCs in orthopedic surgery. A systematic review was conducted utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The studies that used culture-expanded, mesenchymal stem or stromal cells, MSCs and/or connective tissues procured from Wharton's jelly (WJ), from January 2010 to October 2021, were included. Conventional non-operative therapies and placebos were used as comparisons. Six studies that directly discussed WJSCs use in an animal model or the basic scientific testing using an injury model were identified. Five publications studied cartilage injury, three studied degenerative disc disease, one was related to osteoarthritis, and one was related to osteochondral defects. The results of these studies suggested the benefits of WJSCs in the management of these orthopedic pathologies. To adequately assess the safety and efficacy of WJSCs in orthopedic surgery, further randomized controlled clinical studies are necessary.
PubMed: 34832872
DOI: 10.3390/ph14111090 -
Cytotherapy Apr 2021The therapeutic potential of naturally secreted micro- and nanoscale extracellular vesicles (EVs) makes them attractive candidates for regenerative medicine and... (Review)
Review
The therapeutic potential of naturally secreted micro- and nanoscale extracellular vesicles (EVs) makes them attractive candidates for regenerative medicine and pharmaceutical science applications. To date, the results of numerous publications have shown the practicality of using EVs to replace mesenchymal stromal cells (MSCs) or liposomes. This article presents a systematic review of pre-clinical studies conducted over the past decade of MSC-derived EVs (MSC-EVs) used in animal models of disease. The authors searched the relevant literature in the PubMed and Scopus databases (9358 articles), and 690 articles met the inclusion criteria. The eligible articles were placed in the following disease categories: autoimmune, brain, cancer, eye, gastrointestinal, heart, inflammation/transplantation, liver, musculoskeletal, pancreas, spinal cord and peripheral nervous system, respiratory system, reproductive system, skin, urinary system and vascular-related diseases. Next, the eligible articles were assessed for the rate of publication and global distribution, methodology of EV isolation and characterization, route of MSC-EV administration, length of follow-up, source of MSCs and animal species. The current review classifies and critically discusses the technical aspects of these MSC-EV animal studies and discusses potential relationships between methodological details and the effectiveness of MSC-EVs as reported by these pre-clinical studies.
Topics: Animals; Brain; Extracellular Vesicles; Inflammation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 33541780
DOI: 10.1016/j.jcyt.2020.12.009 -
Epilepsia Jul 2022Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and... (Review)
Review
Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.
Topics: Animals; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 35451066
DOI: 10.1111/epi.17266 -
Journal of Orthopaedic Translation Sep 2020Stem cells are considered to be one of the greatest potential treatments to cure degenerative diseases. Stem cells injection for knee osteoarthritis (OA) is still a... (Review)
Review
UNLABELLED
Stem cells are considered to be one of the greatest potential treatments to cure degenerative diseases. Stem cells injection for knee osteoarthritis (OA) is still a relatively new treatment and has not yet gained popularity. So, the effectiveness, safety and potential of mesenchymal stem cells (MSCs) for knee OA treatment is worthy to be explored. Explore the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of knee osteoarthritis. We collected clinical trials using MSCs as treatment for knee OA (before April 2019), including randomized controlled trials (RCTs), retrospective studies and cohort studies. We searched PubMed, EMBASE, Cochrane Library, Web of Science and the ClinicalTrials.gov with keywords (Mesenchymal stem cells [MSCs], Knee osteoarthritis, Effectiveness and Safety), and then performed a systematic review and cumulative metaanalysis of all RCTs and retrospective comparative studies. To evaluate the effectiveness and safety of MSC in knee OA treatment, we applied visual analog scale score, Western Ontario and McMaster Universities Osteo-arthritis Index and adverse events. We included 15 RCTs, two retrospective studies and two cohort studies including a total of 584 knee OA patients in this study. We demonstrated that MSC treatment could significantly decrease visual analog scale in a 12-month follow-up study compared with controls (p < 0.001). MSC therapy also showed significant decreases in Western Ontario and McMaster Universities Osteoarthritis Index scores after the 6-month follow-up (p < 0.001). MSC therapy showed no difference compared with controls (p > 0.05) in adverse events. We suggest that MSC therapy could serve as an effective and safe therapy for clinical application in OA treatment.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE
This study provided the best available evidence and a wider perspective to MSCs application in the management of knee OA. MSCs therapy will have great translational potential in the clinical treatment of various degenerative diseases once optimum formula and explicit target population are identified.
PubMed: 32913710
DOI: 10.1016/j.jot.2020.03.015