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Stem Cell Research & Therapy Jun 2022Mesenchymal stromal cells (MSCs) therapy for acute respiratory distress syndrome (ARDS) is an emerging treatment, but most of the current trials of MSCs stay in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mesenchymal stromal cells (MSCs) therapy for acute respiratory distress syndrome (ARDS) is an emerging treatment, but most of the current trials of MSCs stay in the animal experimental stage, and the safety and efficacy of MSCs in clinical application are not clear. We aimed to analyze the safety, efficacy and biomarkers of mesenchymal stromal cells in the treatment of ARDS.
METHODS
For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of science, CNKI, VIP and Wan Fang data, studies published between database inception and Mar 17, 2022. All randomized controlled trials (RCT) of stem cell interventions for ARDS were included, without language or date restrictions. We did separate meta-analyses for mortality, subjects with adverse events (AEs) and subjects with serious adverse events (SAEs). Since the trials data are dichotomous outcomes, the odds ratio (OR) is adopted for meta-analysis. The quality of the evidence was assessed with the Cochrane risk of bias tool.
FINDINGS
In total, 5 trials involving 171 patients with ARDS were included in this meta-analysis. A total of 99 individuals were randomly assigned to receive MSCs treatment, and 72 were randomly assigned to receive placebo treatment. Treatment with MSCs appeared to increase the occurrence of adverse events, but this result was not statistically significant (OR, 1.58; 95%CI, 0.64-3.91; P = 0.32). The occurrence of serious adverse events was lower in the MSCs group than in the placebo group (OR, 0.57; 95%CI, 0.14-2.32; P = 0.43); there seems to be no significant difference between the two groups in terms of 28 days mortality (OR, 0.93; 95%CI, 0.45-1.89); oxygenation index and biomarkers showed a tendency to improve in treatment, but there was a lack of more statistically significant clinical evidence to support them.
INTERPRETATION
Based on the current clinical trials, MSCs intervention has some safety for ARDS patients, but its effectiveness and predictive value of airspace biomarkers need to be determined by more large-scale, standard randomized controlled trials.
Topics: Humans; Mesenchymal Stem Cells; Respiratory Distress Syndrome
PubMed: 35752865
DOI: 10.1186/s13287-022-02956-3 -
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 -
Veterinary Sciences Nov 2023Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell... (Review)
Review
Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell therapy, which uses mesenchymal stem cells due to their tissue differentiation properties and anti-inflammatory and immunoregulatory effects, aims to restore damaged tissue. In this manuscript, we performed a systematic review using the Parsifal tool, searching the PubMed and Web of Science databases for articles on regenerative medicine for equine musculoskeletal injuries. Our review covers 17 experimental clinical studies categorized by the therapeutic approach used: platelet-rich plasma, conditioned autologous serum, mesenchymal stem cells, and secretome. These therapies reduce healing time, promote regeneration of fibrocartilaginous tissue, improve cellular organization, and improve joint functionality and sustainability. In conclusion, regenerative therapies using platelet-rich plasma, conditioned autologous serum, equine mesenchymal stem cells, and the emerging field of the secretome represent a promising and highly effective approach for the treatment of joint pathologies in horses, implying a valuable advance in equine healthcare.
PubMed: 38133217
DOI: 10.3390/vetsci10120666 -
Advances in Experimental Medicine and... 2022Periodontitis is a chronic inflammatory disease characterized by the loss of tooth-supporting tissues (or periodontium) leading to the formation of periodontal pocket... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periodontitis is a chronic inflammatory disease characterized by the loss of tooth-supporting tissues (or periodontium) leading to the formation of periodontal pocket then to tooth loss. Conventional therapies that involve tooth root debridement are still disappointing because they are more centered on periodontal repair than disease pathophysiology causes. The meta-analysis we present here focused on the results of experimental studies that investigated periodontal mesenchymal stromal cells (MSCs) therapy, a promising strategy to regenerate tissue, given to their immunomodulatory and trophic properties.
METHODS
Using PubMed database and ICTRP search portal, 84 animal and 3 randomized human studies were analyzed.
RESULTS
Overall, our results highlighted that MSCs grafting, regardless of their tissue origin, enhances periodontal regeneration. A defect morphology suitable for an initial clot stabilization increases the procedure efficacy, especially if cells are carried using a vehicle from natural origin. Nevertheless, methodological biases have been highlighted and still limit the translation to human with high prognosis and regulatory considerations. Besides, because only 2 randomized human trials demonstrated the efficacy of the procedure, further studies are needed to investigate periodontal regeneration procedures on experimental models closer to human pathophysiology.
CONCLUSION
Although MSCs grafting in periodontal disease demonstrated therapeutic benefits in animal, it is critical to define more accurately protocols translatable to human and focus on the treatment of the pathology as a whole rather than on the restitution of the sole destroyed tissues.
Topics: Animals; Cell- and Tissue-Based Therapy; Guided Tissue Regeneration, Periodontal; Mesenchymal Stem Cells; Periodontal Ligament; Periodontitis; Periodontium
PubMed: 35612809
DOI: 10.1007/978-3-030-96881-6_20 -
Pharmaceutics May 2022The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells... (Review)
Review
The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs.
PubMed: 35745724
DOI: 10.3390/pharmaceutics14061151 -
FASEB Journal : Official Publication of... May 2017Pericytes are an integral cellular component of vascular structures. Numerous studies have investigated various stem cell types as potential sources of pericytes for... (Review)
Review
Pericytes are an integral cellular component of vascular structures. Numerous studies have investigated various stem cell types as potential sources of pericytes for application in cell-based therapy. The diverse stem cell types and variable experimental protocols of these studies make it imperative to evaluate the relevant scientific literature on the basis of a unified standard. The purpose of this systematic review is to rigorously evaluate the relevant scientific literature for conclusive evidence that stem cells can differentiate into functional pericytes. An online literature search was conducted up to July 2016. Eligible papers were evaluated on 4 pertinent criteria: ) appropriate controls, ) markers to confirm pericyte phenotype, ) techniques for assessing pericyte functionality, and ) differentiation efficiency of the protocol. Our search yielded 20 eligible studies (from 2006 to 2016), 12 of which were published in the past 5 yr. Of these 20 articles, only 1 had positive control, and 5 papers evaluated differentiation efficiency. The most commonly used pericyte markers were neuron-glial antigen 2, platelet-derived growth factor receptor-β, and α-smooth muscle actin. Three articles were associated with adipose stem cells, 4 with mesenchymal stem cells, and 7 with pluripotent stem cells, whereas the remaining 6 articles were based on other miscellaneous stem cell types. Stem cells can serve as a potential source of pericytes, but there should be standardized guidelines in future studies for assessing pericyte differentiation.-Xu, J., Gong, T., Heng, B. C., Zhang, C. F. A systematic review: differentiation of stem cells into functional pericytes.
Topics: Adipocytes; Animals; Cell Differentiation; Coculture Techniques; Endothelial Cells; Humans; Pericytes; Stem Cells
PubMed: 28119398
DOI: 10.1096/fj.201600951RRR -
Arthroscopy : the Journal of... Jan 2021To perform a systematic review and meta-analysis evaluating the effects of mesenchymal stem cells (MSCs) on cartilage regeneration and patient-reported pain and function. (Meta-Analysis)
Meta-Analysis
PURPOSE
To perform a systematic review and meta-analysis evaluating the effects of mesenchymal stem cells (MSCs) on cartilage regeneration and patient-reported pain and function.
METHODS
A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using a PRISMA checklist. The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (2008-2019), EMBASE (2008-2019), and MEDLINE (2008-2019) were queried in July 2019 for literature reporting use of stem cells to treat knee osteoarthritis or chondral defects. Data describing administered treatment, subject population, injection type, duration of follow-up, pain and functional outcomes, and radiographic and magnetic resonance imaging findings were extracted. Risk of bias was assessed using the Downs and Black scale. Meta-analyses adjusted for random effects were performed, calculating pooled effect sizes in terms of patient-reported pain and function, cartilage quality, and cartilage volume.
RESULTS
Twenty-five studies with 439 subjects were identified. There was no significant difference in pain improvement between MSC treatment and controls (pooled standardized mean difference [SMD] = 0.23, P = .30). However, MSC treatment was significantly favored for functional improvement (SMD = 0.66, P < .001). There was improvement in cartilage volume after MSC treatment (SMD = 0.84, P < .001). Regarding cartilage quality, meta-analysis resulted in a small, nonsignificant effect size of 0.37 (95%, -0.03 to 0.77, P = .07). There was risk for potential bias among included studies, with 17 (68%) receiving either a grade of "poor" or "fair."
CONCLUSIONS
The pooled SMD from meta-analyses showed statistically significant effects of MSC on self-reported physical function but not self-reported pain. MSCs provided functional benefit only in patients who underwent concomitant surgery. However, this must be interpreted with caution, as there was substantial variability in MSC composition and mode of delivery. MSC treatment provided significant improvement in cartilage volume but not cartilage quality. Preliminary data regarding therapeutic properties of MSC treatment suggest significant heterogeneity in the current literature, and risk of bias is not negligible.
LEVEL OF EVIDENCE
II, Systematic Review and Meta-analysis.
Topics: Humans; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteoarthritis, Knee
PubMed: 32497658
DOI: 10.1016/j.arthro.2020.05.037 -
Sexual Medicine Reviews Dec 2023Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and...
INTRODUCTION
Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and neurologic factors. Existing treatments for ED mainly focus on symptom relief rather than addressing the underlying cause. Stem cells (SCs) have shown potential as a therapeutic approach for ED due to their anti-inflammatory properties.
OBJECTIVES
This systematic review aims to assess the current status of trials and determine the potential impact of SCs on male sexual health.
METHODS
A comprehensive search strategy was employed to gather relevant articles from 6 electronic databases. The search included articles published until March 2023. The reference lists of articles were manually reviewed to identify additional studies of relevance. The eligibility criteria for inclusion in the analysis focused on clinical trials involving humans that evaluated the safety and efficacy of SC therapy for ED. Exclusion criteria encompassed case reports, case series, abstracts, reviews, and editorials, as well as studies involving animals or SC derivatives. Data extraction was performed via a standardized form with a focus on erectile outcomes.
RESULTS
A total of 2847 articles were initially identified; 18 were included in the final analysis. These studies involved 373 patients with ED and various underlying medical conditions. Multiple types of SC were utilized in the treatment of ED: mesenchymal SCs, placental matrix-derived mesenchymal SCs, mesenchymal SC-derived exosomes, adipose-derived SCs, bone marrow-derived mononuclear SCs, and umbilical cord blood SCs.
CONCLUSION
SC therapy shows promise as an innovative and safe treatment for organic ED. However, the lack of standardized techniques and controlled groups in many studies hampers the ability to evaluate and compare trials.
Topics: Female; Pregnancy; Animals; Male; Humans; Erectile Dysfunction; Quality of Life; Placenta; Stem Cell Transplantation; Penile Erection
PubMed: 37758225
DOI: 10.1093/sxmrev/qead040 -
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