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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 -
Materials Today. Bio Jun 2020The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have... (Review)
Review
The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have focused on enhancing bone regeneration by applying mesenchymal stromal/stem cells (MSCs) in the treatment strategies. Despite the therapeutic efficacy of MSCs in bone regeneration, cell-based therapies are impeded by several challenges in maintaining the optimal cell potency and viability during expansion, storage, and final delivery to patients. Recently, there has been a paradigm shift in therapeutic mechanism of MSCs in tissue repair from one based on cellular differentiation and replacement to one based on secretion and paracrine signaling. Among the broad spectrum of trophic factors, extracellular vesicles particularly the exosomes have been reported to be therapeutically efficacious in several injury/disease indications, including bone defects and diseases. The current systematic review aims to summarize the results of the existing animal studies which were conducted to evaluate the therapeutic efficacy of MSC exosomes for bone regeneration. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, the PubMed and The Cochrane Library database were searched for relevant controlled preclinical animal studies. A total of 23 studies were identified, with the total sample size being 690 rats or mice and 38 rabbits. Generally, MSC exosomes were found to be efficacious for bone regeneration in animal models of bone defects and diseases such as osteonecrosis and osteoporosis. In these studies, MSC exosomes promoted new bone formation with supporting vasculature and displayed improved morphological, biomechanical, and histological outcomes, coupled with positive effects on cell survival, proliferation, and migration, osteogenesis, and angiogenesis. Unclear-to-low risk in bias and incomplete reporting in the primary studies highlighted the need for standardization in outcome measurements and reporting. Further studies in large animal models to establish the safety and efficacy would provide useful information on guiding the design of clinical trials.
PubMed: 32695985
DOI: 10.1016/j.mtbio.2020.100067 -
Journal of Translational Medicine Apr 2023Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment of sepsis. However, the therapeutic effect of EVs is still not universally recognized. Therefore, we conducted this meta-analysis by summarizing data from all published studies that met certain criteria to systematically review the association between EVs treatment and mortality in animal models of sepsis.
METHODS
Systematic retrieval of all studies in PubMed, Cochrane and Web of Science that reported the effects of EVs on sepsis models up to September 2022. The primary outcome was animal mortality. After screening the eligible articles according to inclusion and exclusion criteria, the inverse variance method of fixed effect model was used to calculate the joint odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed by RevMan version 5.4.
RESULTS
In total, 17 studies met the inclusion criteria. Meta-analysis of those studies showed that EVs treatment was associated with reduced mortality in animal models of sepsis (OR 0.17 95% CI: 0.11,0.26, P < 0.001). Further subgroup analysis showed that the mode of sepsis induction, the source, dose, time and method of injection, and the species and gender of mice had no significant effect on the therapeutic effect of EVs.
CONCLUSION
This meta-analysis showed that MSC-EVs treatment may be associated with lower mortality in animal models of sepsis. Subsequent preclinical studies will need to address the standardization of dose, source, and timing of EVs to provide comparable data. In addition, the effectiveness of EVs in treating sepsis must be studied in large animal studies to provide important clues for human clinical trials.
Topics: Mice; Humans; Animals; Disease Models, Animal; Extracellular Vesicles; Mesenchymal Stem Cells; Sepsis; Cell- and Tissue-Based Therapy
PubMed: 37069645
DOI: 10.1186/s12967-023-04121-7 -
ESMO Open 2016Despite decades of intense research, the complex biology of glioblastoma (GBM) is not completely understood. Progression-free survival and overall survival have remained...
Despite decades of intense research, the complex biology of glioblastoma (GBM) is not completely understood. Progression-free survival and overall survival have remained unchanged since the implementation of the STUPP regimen in 2005 with concomitant radio-/chemotherapy and adjuvant chemotherapy with temozolomide. In the context of Hanahan and Weinberg's six hallmarks and two emerging hallmarks of cancer, we discuss up-to-date status and recent research in the biology of GBM. We discuss the clinical impact of the research results with the most promising being in the hallmarks 'enabling replicative immortality', 'inducing angiogenesis', 'reprogramming cellular energetics' and 'evading immune destruction'. This includes the importance of molecular diagnostics according to the new WHO classification and how next generation sequencing is being implemented in the clinical daily life. Molecular results linked together with clinical outcome have revealed the importance of the prognostic biomarker isocitratedehydrogenase (IDH), which is now part of the diagnostic criteria in brain tumours. IDH is discussed in the context of the hallmark 'reprogramming cellular energetics'. O-6-methylguanine-DNA methyltransferase status predicts a more favourable response to treatment and is thus a predictive marker. Based on genomic aberrations, Verhaak have suggested a division of GBM into three subgroups, namely, proneural, classical and mesenchymal, which could be meaningful in the clinic and could help guide and differentiate treatment decisions according to the specific subgroup. The information achieved will develop and improve precision medicine in the future.
PubMed: 28912963
DOI: 10.1136/esmoopen-2016-000144 -
Cells Jan 2023Chronic inflammation has been closely linked to the development and progression of various cancers. The epithelial-mesenchymal transition (EMT) is a process involving... (Review)
Review
Chronic inflammation has been closely linked to the development and progression of various cancers. The epithelial-mesenchymal transition (EMT) is a process involving the acquisition of mesenchymal features by carcinoma cells and is an important link between inflammation and cancer development. Inflammatory mediators in the tumour micro-environment, such as cytokines and chemokines, can promote EMT changes in cancer cells. The aim of this systematic review is to analyse the effect of cytokines on EMT in gynaecological cancers and discuss their possible therapeutic implications. A search of the databases CINAHL, Cochrane, Embase, Medline, PubMed, TRIP, and Web of Science was performed using the keywords: "cytokines" AND "epithelial mesenchymal transition OR transformation" AND "gynaecological cancer". Seventy-one articles reported that various cytokines, such as TGF-β, TNF-α, IL-6, etc., promoted EMT changes in ovarian, cervical, and endometrial cancers. The EMT changes included from epithelial to mesenchymal morphological change, downregulation of the epithelial markers E-cadherin/β-catenin, upregulation of the mesenchymal markers N-cadherin/vimentin/fibronectin, and upregulation of the EMT-transformation factors (EMT-TF) /. Cytokine-induced EMT can lead to gynaecological cancer development and metastasis and hence novel therapies targeting the cytokines or their EMT signalling pathways could possibly prevent cancer progression, reduce cancer recurrence, and prevent drug-resistance.
Topics: Female; Humans; Cytokines; Epithelial-Mesenchymal Transition; Neoplasm Recurrence, Local; Genital Neoplasms, Female; Transforming Growth Factor beta; Tumor Microenvironment
PubMed: 36766756
DOI: 10.3390/cells12030416 -
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 -
Cytotherapy Mar 2023Evidence regarding the extent that mesenchymal stromal cells (MSCs) may improve clinical outcomes in patients with coronavirus disease 2019 (COVID-19) has been limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND AIMS
Evidence regarding the extent that mesenchymal stromal cells (MSCs) may improve clinical outcomes in patients with coronavirus disease 2019 (COVID-19) has been limited by marked inter-study heterogeneity, inconsistent product characterization and appreciable risk of bias (RoB). Given the evolution of treatment options and trajectory of the pandemic, an updated analysis of high-quality evidence from randomized controlled trials is needed for a timely and conclusive understanding of the effectiveness of MSCs.
METHODS
A systematic literature search through March 30, 2022, identified all English language, full-text randomized controlled trials examining the use of MSCs in the treatment of COVID-19.
RESULTS
Eight studies were identified (316 patients, 165 administered MSCs and 151 controls). Controls evolved significantly over time with a broad range of comparison treatments. All studies reported mortality at study endpoint. Random effects meta-analysis revealed that MSCs decreased relative risk of death (risk ratio, 0.63, 95% confidence interval, 0.42-0.94, P = 0.02, I = 14%) with no significant difference in absolute risk of death. MSCs decreased length of hospital stay and C-reactive protein levels and increased odds of clinical improvement at study endpoint compared with controls. Rates of adverse events and severe adverse events were similar between MSC and control groups. Only two (25%) studies reported all four International Society for Cell & Gene Therapy criteria for MSC characterization. Included studies had low (n = 7) or some (n = 1) concerns regarding RoB.
CONCLUSIONS
MSCs may reduce risk of death in patients with severe or critical COVID-19 and improve secondary clinical outcomes. Variable outcome reporting, inconsistent product characterization and variable control group treatments remain barriers to higher-quality evidence and may constrain clinical usage. A master protocol is proposed and appears necessary for accelerated translation of higher-quality evidence for future applications of MSC therapy.
Topics: Humans; COVID-19; SARS-CoV-2; Randomized Controlled Trials as Topic; Pandemics; Mesenchymal Stem Cells
PubMed: 36333234
DOI: 10.1016/j.jcyt.2022.10.003 -
The Physician and Sportsmedicine 2016Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics,... (Review)
Review
OBJECTIVES
Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI). The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment.
METHODS
A literature search was executed using Medline, Cochrane, and Embase with keywords "knee osteoarthritis" and "injection." Specifically, 45 articles that discussed intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSC), were analyzed. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5 evidence. Papers included animal models.
RESULTS
Local anesthetics have potential side effects and may only be effective for a few hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation . Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint.
CONCLUSIONS
Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they may ultimately have profound implications in the way knee OA is managed.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthroplasty, Replacement, Knee; Braces; Humans; Hyaluronic Acid; Injections, Intra-Articular; Mesenchymal Stem Cell Transplantation; Osteoarthritis, Knee; Pain; Platelet-Rich Plasma; Viscosupplements
PubMed: 26985986
DOI: 10.1080/00913847.2016.1168272 -
Frontiers in Pharmacology 2022Radioresistance remains a significant challenge in tumor therapy. This systematic review aims to demonstrate the role of long non-coding RNA (lncRNA) in cancer... (Review)
Review
Radioresistance remains a significant challenge in tumor therapy. This systematic review aims to demonstrate the role of long non-coding RNA (lncRNA) in cancer radioresistance/radiosensitivity. The electronic databases Pubmed, Embase, and Google Scholar were searched from January 2000 to December 2021 to identify studies addressing the mechanisms of lncRNAs in tumor radioresistance/sensitivity, each of which required both and experiments. Among the 87 studies identified, lncRNAs were implicated in tumor radioresistance/sensitivity mainly in three paradigms. 1) lncRNAs act on microRNA (miRNA) by means of a sponge, and their downstream signals include some specific molecular biological processes (DNA repair and chromosome stabilization, mRNA or protein stabilization, cell cycle and proliferation, apoptosis-related pathways, autophagy-related pathways, epithelial-mesenchymal transition (EMT), cellular energy metabolism) and some signaling mediators (transcription factors, kinases, some important signal transduction pathways) that regulate various biological processes. 2) lncRNAs directly interact with proteins, affecting the cell cycle and autophagy to contribute to tumor radioresistance. 3) lncRNAs act like transcription factors to initiate downstream signaling pathways and participate in tumor radioresistance. lncRNAs are important regulators involved in tumor radioresistance\sensitivity. Different lncRNAs may participate in the radioresistance with the same regulatory paradigm, and the same lncRNAs may also participate in the radioresistance in different ways. Future research should focus more on comprehensively characterizing the mechanisms of lncRNAs in tumor radioresistance to help us identify corresponding novel biomarkers and develop new lncRNA-based methods to improve radioresistance.
PubMed: 35600868
DOI: 10.3389/fphar.2022.879704 -
Cytotherapy Jun 2022Mesenchymal stem/stromal cells (MSCs) and their secreted products are a promising therapy for COVID-19 given their immunomodulatory and tissue repair capabilities. Many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mesenchymal stem/stromal cells (MSCs) and their secreted products are a promising therapy for COVID-19 given their immunomodulatory and tissue repair capabilities. Many small studies were launched at the onset of the pandemic, and repeated meta-analysis is critical to obtain timely and sufficient statistical power to determine efficacy.
METHODS AND FINDINGS
All English-language published studies identified in our systematic search (up to February 3, 2021) examining the use of MSC-derived products to treat patients with COVID-19 were identified. Risk of bias (RoB) was assessed for all studies. Nine studies were identified (189 patients), four of which were controlled (93 patients). Three of the controlled studies reported on mortality (primary analysis) and were pooled through random-effects meta-analysis. MSCs decreased the risk of death at study endpoint compared with controls (risk ratio, 0.18; 95% confidence interval [CI], 0.04 to 0.74; P = .02; I = 0%), although follow-up differed. Among secondary outcomes, interleukin-6 levels were most commonly reported and were decreased compared with controls (standardized mean difference, -0.69; 95% CI, -1.15 to -0.22; P = .004; I = 0%) (n = 3 studies). Other outcomes were not reported consistently, and pooled estimates of effect were not performed. Substantial heterogeneity was observed between studies in terms of study design. Adherence to published ISCT criteria for MSC characterization was low. In two of nine studies, RoB analysis revealed a low to moderate risk of bias in controlled studies, and uncontrolled case series were of good (3 studies) or fair (2 studies) quality.
CONCLUSION
Use of MSCs to treat COVID-19 appears promising; however, few studies were identified, and potential risk of bias was detected in all studies. More controlled studies that report uniform clinical outcomes and use MSC products that meet standard ISCT criteria should be performed. Future iterations of our systematic search should refine estimates of efficacy and clarify potential adverse effects.
Topics: COVID-19; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pandemics; SARS-CoV-2
PubMed: 35219584
DOI: 10.1016/j.jcyt.2021.12.001