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Cancers Jul 2022Circulating tumor cells (CTCs) play a key role in hematogenous metastasis and post-surgery recurrence. In hepatocellular carcinoma (HCC), CTCs have emerged as a valuable... (Review)
Review
Clinical Implication of Circulating Tumor Cells Expressing Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) Markers and Their Perspective in HCC: A Systematic Review.
Circulating tumor cells (CTCs) play a key role in hematogenous metastasis and post-surgery recurrence. In hepatocellular carcinoma (HCC), CTCs have emerged as a valuable source of therapeutically relevant information. Certain subsets or phenotypes of CTCs can survive in the bloodstream and induce metastasis. Here, we performed a systematic review on the importance of epithelial-mesenchymal transition (EMT)-CTCs and circulating cancer stem cells (CCSCs) in metastatic processes and their prognostic power in HCC management. PubMed, Scopus, and Embase databases were searched for relevant publications. PRISMA criteria were used to review all studies. Twenty publications were eligible, of which 14, 5, and 1 study reported EMT-CTCs, CCSCs, and both phenotypes, respectively. Most studies evaluated that mesenchymal CTCs and CCSCs positivity were statistically associated with extensive clinicopathological features, including larger size and multiple numbers of tumors, advanced stages, micro/macrovascular invasion, and metastatic/recurrent disease. A preliminary meta-analysis showed that the presence of mesenchymal CTCs in pre- and postoperative blood significantly increased the risk of early recurrence. Mesenchymal-CTCs positivity was the most reported association with inferior outcomes based on the prognosis of HCC recurrence. Our finding could be a step forward, conveying additional prognostic values of CTC subtypes as promising biomarkers in HCC management.
PubMed: 35884432
DOI: 10.3390/cancers14143373 -
Journal of Clinical Medicine Dec 2023Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to... (Review)
Review
BACKGROUND
Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers.
METHODS
A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates.
RESULTS
Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration.
CONCLUSIONS
MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.
PubMed: 38137625
DOI: 10.3390/jcm12247545 -
Materials (Basel, Switzerland) Aug 2021The use of biological templates for the suitable growth of adipose-derived mesenchymal stem cells (AD-MSC) and "neo-tissue" construction has exponentially increased over... (Review)
Review
The use of biological templates for the suitable growth of adipose-derived mesenchymal stem cells (AD-MSC) and "neo-tissue" construction has exponentially increased over the last years. The bioengineered scaffolds still have a prominent and biocompatible framework playing a role in tissue regeneration. In order to supply AD-MSCs, biomaterials, as the stem cell niche, are more often supplemented by or stimulate molecular signals that allow differentiation events into several strains, besides their secretion of cytokines and effects of immunomodulation. This systematic review aims to highlight the details of the integration of several types of biomaterials used in association with AD-MSCs, collecting notorious and basic data of in vitro and in vivo assays, taking into account the relevance of the interference of the cell lineage origin and handling cell line protocols for both the replacement and repairing of damaged tissues or organs in clinical application. Our group analyzed the quality and results of the 98 articles selected from PubMed, Scopus and Web of Science. A total of 97% of the articles retrieved demonstrated the potential in clinical applications. The synthetic polymers were the most used biomaterials associated with AD-MSCs and almost half of the selected articles were applied on bone regeneration.
PubMed: 34443163
DOI: 10.3390/ma14164641 -
Orthopaedic Journal of Sports Medicine Jun 2021The outcomes after high tibial osteotomy (HTO) with augmentation of intra-articular mesenchymal stem cell (MSCs) for medial tibiofemoral osteoarthritis remain... (Review)
Review
BACKGROUND
The outcomes after high tibial osteotomy (HTO) with augmentation of intra-articular mesenchymal stem cell (MSCs) for medial tibiofemoral osteoarthritis remain controversial.
PURPOSE
To pool existing studies to compare the outcomes of HTO with versus without intra-articular MSC augmentation when performed for medial tibiofemoral osteoarthritis.
STUDY DESIGN
Systematic review; Level of evidence, 3.
METHODS
The systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included were clinical studies that compared the outcomes of HTO with intra-articular MSC augmentation (MSC group) versus without (control group). Pre- and postoperative outcomes were compared between groups from measures including the Lysholm score, International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score, Hospital for Special Surgery Knee Rating Scale, Tegner score, visual analog scale for pain, arthroscopic and histological grading scales, femorotibial angle, weightbearing line, and posterior tibial slope.
RESULTS
We reviewed 4 studies with a total of 224 patients. The MSC group demonstrated significantly greater improvement versus controls in the pooled Lysholm score (weighted mean difference [WMD], 6.64; 95% CI, 0.90 to 12.39) and pooled IKDC score (WMD, 9.21; 95% CI, 4.06 to 14.36), which were within or close to the minimal clinically important difference. Radiological outcomes were similar in both groups, including the femorotibial angle (WMD, -0.01; 95% CI, -1.10 to 1.09), weightbearing line, and posterior tibial slope. The studies were homogeneous, and no publication bias was noted.
CONCLUSION
Intra-articular MSC augmentation for HTO may modestly improve functional outcomes as compared with HTO alone. However, adequate data are lacking to make definitive conclusions regarding the effect of MSC augmentation on pain or arthroscopic and histologic grading.
PubMed: 34212066
DOI: 10.1177/23259671211014840 -
Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
Frontiers in Genetics 2022Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding...
Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding and non-coding genes, and bioactive substances. Exosomes participate in information transmission between cells and regulate processes such as cell proliferation, migration, angiogenesis, and phenotypic transformation. They have broad prospects in the occurrence, development, and treatment of many diseases including orthopedics. Exosomes derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, osteoclasts, and their precursors are recognized to play pivotal roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. This articlesummarizes the characteristics of exosomes and their research progress in bone remodeling, bone tumors, vascular skeletal muscle injury, spinal cord injury, degenerative disc diseases, cartilage degeneration, osteoarthritis, necrosis of the femoral head, and osteoporosis.
PubMed: 36081990
DOI: 10.3389/fgene.2022.915141 -
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 -
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 -
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 -
Cell Transplantation Dec 2018Exogenous stem cell therapy (SCT) has been recognized recently as a promising neuroregenerative strategy to augment recovery in stroke survivors. Mesenchymal stem cells...
Exogenous stem cell therapy (SCT) has been recognized recently as a promising neuroregenerative strategy to augment recovery in stroke survivors. Mesenchymal stem cells (MSCs) are the primary source of stem cells used in the majority of both pre-clinical and clinical studies in stroke. In the absence of evidence-based guidelines on the use of SCT in stroke patients, understanding the progress of MSC research across published studies will assist researchers and clinicians in better achieving success in translating research. We conducted a systematic review on published literature using MSCs in both pre-clinical studies and clinical trials between 2008 and 2017 using the public databases PubMed and Ovid Medline, and the clinical trial registry ( www.clinicaltrials.gov ). A total of 78 pre-clinical studies and eight clinical studies were identified. While majority of the pre-clinical and clinical studies demonstrated statistically significant effects, the clinical significance of these findings was still unclear. Effect sizes could not be measured mainly due to reporting issues in pre-clinical studies, thus limiting our ability to compare results across studies quantitatively. The overall quality of both pre-clinical and clinical studies was sub-optimal. By conducting a systematic review of both pre-clinical and clinical studies on MSCs therapy in stroke, we assessed the quality of current evidence and identified several issues and gaps in translating animal studies to human trials. Addressing these issues and incorporating changes into future animal studies and human trials may lead to better success of stem cells-based therapeutics in the near future.
Topics: Animals; Clinical Trials as Topic; Databases, Factual; Drug Evaluation, Preclinical; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Stroke
PubMed: 30343609
DOI: 10.1177/0963689718806846