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Journal of Translational Medicine Jan 2021The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial... (Meta-Analysis)
Meta-Analysis Review
The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial-mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial-mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.
Topics: Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Neoplasm Grading; Prognosis; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 33413466
DOI: 10.1186/s12967-020-02644-x -
Neural Regeneration Research Jul 2024Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may...
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may improve symptoms, no treatment can cure or reverse the disease itself. Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson's disease. Mesenchymal stem cells are considered a promising option due to fewer ethical concerns, a lower risk of immune rejection, and a lower risk of teratogenicity. We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function, memory, and preservation of dopaminergic neurons in a Parkinson's disease animal model. We searched bibliographic databases (PubMed/MEDLINE, Embase, CENTRAL, Scopus, and Web of Science) to identify articles and included only peer-reviewed in vivo interventional animal studies published in any language through June 28, 2023. The study utilized the random-effect model to estimate the 95% confidence intervals (CI) of the standard mean differences (SMD) between the treatment and control groups. We use the systematic review center for laboratory animal experimentation's risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment. A total of 33 studies with data from 840 Parkinson's disease model animals were included in the meta-analysis. Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test. Among the stem cell types, the bone marrow MSCs with neurotrophic factor group showed largest effect size (SMD [95% CI] = -6.21 [-9.50 to -2.93], P = 0.0001, I2 = 0.0 %). The stem cell treatment group had significantly more tyrosine hydroxylase positive dopaminergic neurons in the striatum ([95% CI] = 1.04 [0.59 to 1.49], P = 0.0001, I2 = 65.1 %) and substantia nigra (SMD [95% CI] = 1.38 [0.89 to 1.87], P = 0.0001, I2 = 75.3 %), indicating a protective effect on dopaminergic neurons. Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route (SMD [95% CI] = -2.59 [-3.25 to -1.94], P = 0.0001, I2 = 74.4 %). The memory test showed significant improvement only in the intravenous route (SMD [95% CI] = 4.80 [1.84 to 7.76], P = 0.027, I2 = 79.6 %). Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson's disease. Further research is required to determine the optimal stem cell types, modifications, transplanted cell numbers, and delivery methods for these protocols.
PubMed: 38051903
DOI: 10.4103/1673-5374.387976 -
International Journal of Molecular... Feb 2023Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the... (Meta-Analysis)
Meta-Analysis Review
Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the exploration of new therapies to regenerate cartilage before significant deterioration and subsequent joint replacement take place. Recent studies have investigated a multitude of mesenchymal stem cell (MSC) sources and polymer scaffold compositions. It is uncertain how different combinations affect the extent of integration of native and implant cartilage and the quality of new cartilage formed. Implants seeded with bone marrow-derived MSCs (BMSCs) have demonstrated promising results in restoring these defects, largely through in vitro and animal studies. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL) to identify studies using BMSC-seeded implants in animal models of focal cartilage defects of the knee. Quantitative results from the histological assessment of integration quality were extracted. Repair cartilage morphology and staining characteristics were also recorded. Meta-analysis demonstrated that high-quality integration was achieved, exceeding that of cell-free comparators and control groups. This was associated with repair tissue morphology and staining properties which resembled those of native cartilage. Subgroup analysis showed better integration outcomes for studies using poly-glycolic acid-based scaffolds. In conclusion, BMSC-seeded implants represent promising strategies for the advancement of focal cartilage defect repair. While a greater number of studies treating human patients is necessary to realize the full clinical potential of BMSC therapy, high-quality integration scores suggest that these implants could generate repair cartilage of substantial longevity.
Topics: Animals; Humans; Cartilage, Articular; Tissue Engineering; Bone Marrow; Cartilage Diseases; Tissue Scaffolds; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation
PubMed: 36834639
DOI: 10.3390/ijms24043227 -
Diagnostics (Basel, Switzerland) Aug 2022Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed... (Review)
Review
Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.
PubMed: 36010357
DOI: 10.3390/diagnostics12082004 -
Biomedicines Dec 2022Producing tremendous amounts of stress and financial burden on the global patient population and healthcare systems around the world, most current modalities of... (Review)
Review
Producing tremendous amounts of stress and financial burden on the global patient population and healthcare systems around the world, most current modalities of treatment for musculoskeletal ailments often do not address the etiopathogenetic causes of these disorders. Regenerative medicine for musculoskeletal disorders relies on orthobiologics derived from either allogenic or autologous sources. Multiple drawbacks are associated with autologous sources, including donor-site morbidity, a dearth of studies, and variability in both patient reported and clinical/functional outcomes. On the other hand, allogenic sources address several of these concerns, and continue to be a suitable source of mesenchymal stem cells (MSCs). This review qualitatively reports both the preclinical and clinical outcomes of publications studying the applications of umbilical cord (-derived Wharton's jelly), amniotic suspension allograft, amniotic membrane, and amniotic fluid in musculoskeletal medicine. A systematic review was conducted utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines on studies published between January 2010 and October 2022 that used allogeneic perinatal tissues. Further randomized controlled clinical studies are necessary to properly evaluate the safety and efficacy of these tissues in orthopedic surgery.
PubMed: 36551929
DOI: 10.3390/biomedicines10123173 -
Cancer Cell International Jun 2022The oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific... (Review)
Review
BACKGROUND
The oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific functions of DCLK1 have shed new light on different functions of DCLK1 short (DCLK1-S) and DCLK1 long (DCLK1-L) isoforms in tumor initiation, growth, and metastasis. Therefore, the current systematic review and meta-analysis aimed to review the available in vitro, in vivo, and clinical evidence on the oncogenic roles and clinical significance of DCLK1 isoforms in colorectal cancer.
METHODS
The literature databases of PubMed, Scopus, ISI Web of Science, and Embase were searched to identify eligible articles. The description characteristics of in vitro and pre-clinical studies were extracted from identified reports. In addition, hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded to determine the relationships between DCLK1-L and DCLK1-S expression and prognostic outcomes in patients with CRC.
RESULTS
Both in vitro and in vivo evidence have emphasized the potential oncogenic functions of DCLK1 in tumor initiation, self-renewal ability, tumor invasion, epithelial-mesenchymal transition (EMT), and metastasis. However, the anti-DCLK1 antibodies generally utilized in these studies could detect sequence homology epitopes of both isoforms. Recent limited isoform-specific evidence has strongly supported the significant positive expression and rather oncogenic efficacy of DCLK1-S in tumorigenesis, EMT, and invasion compared with DCLK1-L in human CRC cell lines. Our meta-analysis findings of limited clinical studies indicated that only overexpression of DCLK1-S is associated with worse overall survival (OS) (HR = 7.930, 95% CI 2.252-27.924, p = 0.001). Increased expression of both DCLK1-S (HR = 1.610, 95% CI 1.020-2.541, p = 0.041) and DCLK1-L (HR = 5.890, 95% CI 1.219-28.453, p = 0.027) isoforms was closely associated with worse DSS/CSS in CRC patients. Furthermore, the high expression of DCLK1-S was found to be associated with poor DFS/RFS/PFS (HR = 1.913, 95% CI 1.230-2.973, p = 0.004).
CONCLUSIONS
The current findings strongly supported that the DCLK1-S isoform may play a crucial role in the invasion, aggressive tumor behavior, and worsened survival outcomes of CRC patients. However, further critical investigations related to the potential preclinical and clinical utilities of DCLK1-S as a specific CRC-CSC marker are warranted.
PubMed: 35717205
DOI: 10.1186/s12935-022-02632-9 -
Journal of Cellular Physiology Dec 2022Three-dimensional (3D) cell cultures represent the spontaneous state of stem cells with specific gene and protein molecular expression that are more alike the in vivo... (Review)
Review
Three-dimensional (3D) cell cultures represent the spontaneous state of stem cells with specific gene and protein molecular expression that are more alike the in vivo condition. In vitro two-dimensional (2D) cell adhesion cultures are still commonly employed for various cellular studies such as movement, proliferation and differentiation phenomena; this procedure is standardized and amply used in laboratories, however their representing the original tissue has recently been subject to questioning. Cell cultures in 2D require a support/substrate (flasks, multiwells, etc.) and use of fetal bovine serum as an adjuvant that stimulates adhesion that most likely leads to cellular aging. A 3D environment stimulates cells to grow in suspended aggregates that are defined as "spheroids." In particular, adipose stem cells (ASCs) are traditionally observed in adhesion conditions, but a recent and vast literature offers many strategies that obtain 3D cell spheroids. These cells seem to possess a greater ability in maintaining their stemness and differentiate towards all mesenchymal lineages, as demonstrated in in vitro and in vivo studies compared to adhesion cultures. To date, standardized procedures that form ASC spheroids have not yet been established. This systematic review carries out an in-depth analysis of the 76 articles produced over the past 10 years and discusses the similarities and differences in materials, techniques, and purposes to standardize the methods aimed at obtaining ASC spheroids as already described for 2D cultures.
Topics: Adipocytes; Adipose Tissue; Artifacts; Cell Culture Techniques; Spheroids, Cellular; Stem Cells
PubMed: 36209478
DOI: 10.1002/jcp.30892 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2022Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common...
BACKGROUND
Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common solid sarcoma in children. The most usual site of occurrence are the head and neck regions. RMS presents a variety of histologic features, and so differential diagnosis with other small round cell tumors is needed. Hence, it has been very useful to the field to undertake additional immunohistochemical studies to determine the diagnosis and, on occasions, to assign subtype tumors.
MATERIAL AND METHODS
A systematic review of three databases (Medline, Biological Science Collection and Health & Medical Collection) was carried out with the purpose of analyzing rhabdomyosarcoma cases reported in the literature, specifically with localization in the head and neck regions in children. This strategy allowed us to identify the main anatomical site of appearance, the subtype of RMS, average age, histologic characteristics and immunohistochemistry markers used in a usual and any additional way.
RESULTS
According to the selection criteria in this systematic review, twelve articles, and fourteen cases were identified that highlight that the histological diagnosis usually presents cellular heterogeneity. Therefore, immunohistochemistry is needed to confirm the diagnosis.
CONCLUSIONS
Histologic characterization is not always sufficient for a conclusive diagnosis of RMS. Therefore, immunohistochemistry is helpful to determine the subtype and consequently, sometimes the behavior, treatment and prognosis. Additional markers may vary according to the institution and the need of particular cases.
Topics: Child; Humans; Rhabdomyosarcoma; Immunohistochemistry; Prognosis; Diagnosis, Differential
PubMed: 36173721
DOI: 10.4317/medoral.25508 -
Biomedicines Nov 2022Fibroblasts have an important role in the maintenance of the extracellular matrix of connective tissues by producing and remodelling extracellular matrix proteins. They... (Review)
Review
Fibroblasts have an important role in the maintenance of the extracellular matrix of connective tissues by producing and remodelling extracellular matrix proteins. They are indispensable for physiological processes, and as such also associate with many pathological conditions. In recent years, a number of studies have identified donor-derived fibroblasts in various tissues of bone marrow transplant recipients, while others could not replicate these findings. In this systematic review, we provide an overview of the current literature regarding the differentiation of hematopoietic stem cells into fibroblasts in various tissues. PubMed, Embase, and Web of Science (Core Collection) were systematically searched for original articles concerning fibroblast origin after hematopoietic stem cell transplantation in collaboration with a medical information specialist. Our search found 5421 studies, of which 151 were analysed for full-text analysis by two authors independently, resulting in the inclusion of 104 studies. Only studies in animals and humans, in which at least one marker was used for fibroblast identification, were included. The results were described per organ of fibroblast engraftment. We show that nearly all mouse and human organs show evidence of fibroblasts of hematopoietic stem cell transfer origin. Despite significant heterogeneity in the included studies, most demonstrate a significant presence of fibroblasts of hematopoietic lineage in non-hematopoietic tissues. This presence appears to increase after the occurrence of tissue damage.
PubMed: 36551819
DOI: 10.3390/biomedicines10123063 -
Stem Cell Research & Therapy Jul 2021Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies.
METHODS
The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases.
RESULTS
Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV).
CONCLUSION
This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.
Topics: Animals; Bone Regeneration; Bone and Bones; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis
PubMed: 34215342
DOI: 10.1186/s13287-021-02456-w