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Medicina (Kaunas, Lithuania) Jan 2023Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic... (Review)
Review
Efficacy of Adipose-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction Alone and Combined to Biomaterials in Tendinopathy or Tendon Injury: Systematic Review of Current Concepts.
Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications.
Topics: Animals; Humans; Stromal Vascular Fraction; Biocompatible Materials; Mesenchymal Stem Cells; Tendinopathy; Tendons
PubMed: 36837474
DOI: 10.3390/medicina59020273 -
BMJ (Clinical Research Ed.) Sep 2021To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).
STUDY SELECTION
Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate.
METHODS
After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm.
RESULTS
As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative.
CONCLUSION
In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol established a priori is included as a data supplement.
FUNDING
This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321).
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).
Topics: Antibodies, Monoclonal; Antibodies, Viral; Antiviral Agents; Bayes Theorem; COVID-19; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Humans; Immunization, Passive; Network Meta-Analysis; SARS-CoV-2; Treatment Outcome; COVID-19 Serotherapy
PubMed: 34556486
DOI: 10.1136/bmj.n2231 -
BMJ Open Nov 2022The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA).
DESIGN
Systematic review and meta-analysis.
PARTICIPANTS
Patients with KOA.
INTERVENTIONS
Use of MSCs+PRP.
PRIMARY AND SECONDARY OUTCOMES
Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and adverse reactions.
DATA SOURCES
PubMed, Cochrane Library, Embase and China National Knowledge Infrastructure were searched from inception to 15 July 2021.
MEASURES
The OR or weighted mean difference (WMD) of relevant outcome indicators was calculated. Study quality was evaluated using the risk-of-bias assessment tool version 2.0. Heterogeneity among studies was evaluated by calculating I. If I<50%, a fixed-effect model was applied; conversely, if I ≥50%, a random-effect model was applied.
RESULTS
Six controlled clinical trials with 493 cases were included. The meta-analysis results showed that in terms of the VAS score 3 months after treatment, MSCs+PRP had no significant effect on the reduction of the VAS score in patients with KOA compared with the control (p=0.09), hyaluronic acid (HA) (p=0.15) or PRP alone (p=0.07). MSCs+PRP was more effective in reducing the VAS score at 6 and 12 months after treatment than the control (WMD=-0.55, 95% CI -0.87 to -0.22, p<0.001), HA (WMD=-1.20, 95% CI -2.28 to -0.13, p=0.03) or PRP alone (WMD=-0.54, 95% CI -0.89 to -0.18, p=0.003). Regarding the decrease in the total WOMAC score at 3 and 6 months after treatment, MSCs+PRP showed better clinical efficacy than the control or HA alone (p<0.01). Compared with the control, MSCs+PRP exhibited no significant difference in reducing the total WOMAC score 12 months after treatment (p=0.39). There was no significant difference between MSCs+PRP and the control in terms of improvement of the KOOS 12 months after treatment (p=0.16). Compared with MSCs alone, MSCs+PRP exhibited no significant difference in the incidence of adverse reactions (p=0.22) 12 months after treatment.
CONCLUSIONS
Treatment with MSCs+PRP showed good clinical efficacy in improving pain and joint function in patients with KOA. Compared with MSCs alone, there was no significant difference in the incidence of adverse reactions with MSCs+PRP.
PROSPERO REGISTRATION NUMBER
CRD 42021275830.
Topics: Humans; Hyaluronic Acid; Injections, Intra-Articular; Mesenchymal Stem Cells; Osteoarthritis, Knee; Platelet-Rich Plasma; Randomized Controlled Trials as Topic
PubMed: 36385022
DOI: 10.1136/bmjopen-2022-061008 -
Cell and Tissue Research Mar 2021Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic... (Review)
Review
Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.
Topics: Animals; Cicatrix, Hypertrophic; Humans; Keloid; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Wound Healing
PubMed: 33386995
DOI: 10.1007/s00441-020-03361-z -
Orthopaedic Journal of Sports Medicine Nov 2022Multiple studies have investigated the use of mesenchymal stem cells (MSCs) for patients undergoing high tibial osteotomy (HTO), and the effectiveness thereof remains... (Review)
Review
BACKGROUND
Multiple studies have investigated the use of mesenchymal stem cells (MSCs) for patients undergoing high tibial osteotomy (HTO), and the effectiveness thereof remains controversial.
PURPOSE
To analyze the effectiveness of intra-articular MSC injection in patients who underwent HTO in terms of clinical outcomes, radiological outcomes, and cartilage repair by a meta-analysis of the available literature.
STUDY DESIGN
Systematic review; Level of evidence, 3.
METHODS
The electronic databases of PubMed, Embase, Web of Science, and the Cochrane Library were searched from their inception to October 30, 2021, for comparative studies between patients who underwent HTO with and without intra-articular injection of MSCs, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Study quality was assessed by the Coleman Methodology Score (CMS). Data with comparable results were pooled for meta-analysis. The primary outcomes of interest were the Hospital for Special Surgery (HSS), International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), and Lysholm scores, as well as the International Cartilage Regeneration & Joint Preservation Society (ICRS) grade of cartilage repair. Radiological outcomes including femorotibial angle, posterior tibial slope, and hip-knee-ankle (HKA) angle were included as secondary outcomes. A fixed-model effect was used for meta-analyses with low heterogeneity between studies ( < 25%), while the random-model effect was used for medium- to high-heterogeneity analyses ( ≥ 25%).
RESULTS
A total of 843 studies were screened, of which 6 studies with 452 patients met the inclusion criteria and were included. The mean CMS was 81.17. Patients with MSC injection had significantly higher Lysholm scores ( = .007) and HSS scores ( = .01) and higher proportions of ICRS grade 1 ( = .03) and grade 2 ( = .02) cartilage repair in the medial femoral condyle and grade 2 cartilage repair in the tibial plateau ( = .04). There were no significant differences between groups in the IKDC score, KOOS Pain and Symptoms subscales, femorotibial angle, posterior tibial slope, or HKA angle.
CONCLUSION
Intra-articular MSC injection may enhance the cartilage repair for patients who undergo HTO. However, evidence of improvement in knee functions remains limited.
REGISTRATION
CRD42021291345 (PROSPERO).
PubMed: 36452339
DOI: 10.1177/23259671221133784 -
The application and progress of stem cells in auricular cartilage regeneration: a systematic review.Frontiers in Cell and Developmental... 2023The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is... (Review)
Review
The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is constructing the scaffold for auricular reconstruction. As a type of cell with multiple differentiation potentials, stem cells play an essential role in the construction of cartilage scaffolds, and therefore have received widespread attention in ear reconstructive research. A literature search was conducted for peer-reviewed articles between 2005 and 2023 with the following keywords: stem cells; auricular cartilage; ear cartilage; conchal cartilage; auricular reconstruction, regeneration, and reparation of chondrocytes; tissue engineering in the following databases: PubMed, MEDLINE, Cochrane, and Ovid. Thirty-three research articles were finally selected and their main characteristics were summarized. Adipose-derived stem cells (ADSCs), bone marrow mesenchymal stem cells (BMMSCs), perichondrial stem/progenitor cells (PPCs), and cartilage stem/progenitor cells (CSPCs) were mainly used in chondrocyte regeneration. Injecting the stem cells into the cartilage niche directly, co-culturing the stem cells with the auricular cartilage cells, and inducing the cells in the chondrogenic medium were the main methods that have been demonstrated in the studies. The chondrogenic ability of these cells was observed , and they also maintained good elasticity and morphology after implantation for a period of time. ADSC, BMMSC, PPC, and CSPC were the main stem cells that have been researched in craniofacial cartilage reconstruction, the regenerative cartilage performed highly similar to normal cartilage, and the test of AGA and type II collagen content also proved the cartilage property of the neo-cartilage. However, stem cell reconstruction of the auricle is still in the initial stage of animal experiments, transplantation with such scaffolds in large animals is still lacking, and there is still a long way to go.
PubMed: 37564374
DOI: 10.3389/fcell.2023.1204050 -
Cancers Oct 2021PEComas is a family of rare mesenchymal tumors. This systematic review aims to better understand the natural history of advanced PEComas. After a search on the PubMed... (Review)
Review
PEComas is a family of rare mesenchymal tumors. This systematic review aims to better understand the natural history of advanced PEComas. After a search on the PubMed database and main oncology meeting libraries according to the PRISMA guidelines, 88 articles reported in the English literature were included. Data on clinical and histological features, treatments and outcomes were collected. To identify risk factors, univariate and multivariate analyses were performed. Seven cohorts of patients and 124 individual patients were identified. Focusing on case reports, most patients were metastatic, and the median overall survival (OS) of the entire cohort was 60 months (95%CI 33; NA). Risk factors significantly associated with OS in the multivariate analysis were the presence of metastasis at diagnosis (HR: 2.59, 95%CI 1.06; 6.33, = 0.036) and the grouped-Bleeker's risk category (HR: 4.66; 95%CI 1.07; 20.19; = 0.039). In the metastatic population, only the presence of lymph node metastasis was associated with OS (HR: 3.11; 95%CI 1.13; 8.60, < 0.05). Due to a lack of events, it was not possible to conclude on other factors. This review of the literature highlights the heterogeneity of literature data and shows the great diversity of clinical management strategies.
PubMed: 34680376
DOI: 10.3390/cancers13205227 -
Scientific Reports May 2024Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a... (Meta-Analysis)
Meta-Analysis
Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = - 0.57, 95% CI [- 1.08, - 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = - 7.05, 95% CI [- 10.69, - 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.
Topics: Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Treatment Outcome
PubMed: 38822024
DOI: 10.1038/s41598-024-62726-4 -
Stem Cell Research & Therapy Sep 2022Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal... (Meta-Analysis)
Meta-Analysis Review
The optimal transplantation strategy of umbilical cord mesenchymal stem cells in spinal cord injury: a systematic review and network meta-analysis based on animal studies.
OBJECTIVE
Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future.
METHODS
Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction.
RESULTS AND DISCUSSION
A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 10) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 10), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future.
Topics: Animals; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Network Meta-Analysis; Spinal Cord Injuries; Umbilical Cord
PubMed: 36056386
DOI: 10.1186/s13287-022-03103-8 -
Dentistry Journal Oct 2023The aim of this systematic review is to describe and identify the prospects of β-Tricalcium Phosphate (β-TCP) as an alveolar bone grafting (ABG) material in cleft... (Review)
Review
The aim of this systematic review is to describe and identify the prospects of β-Tricalcium Phosphate (β-TCP) as an alveolar bone grafting (ABG) material in cleft lip/palate (CL/P) or alveolar bone cleft defects. A systematic review protocol based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted using MEDLINE/PubMed, Web of Science/ISI Web of Knowledge, Scopus, and the Cochrane Library, with English as the inclusion criterion and no publication year limits. The keywords yielded a total of 5824 publications. After removing duplicates and non-English articles, there were 3196 suitable articles available for evaluation. Subsequently, 1315 studies remained after reviewing titles and abstracts. Furthermore, 85 full articles were assessed for eligibility. After reading the complete texts of those papers, 20 were eventually selected that matched the inclusion requirements. Thirteen out of the twenty studies included in this systematic review were deemed to have a low risk of bias; one had a high risk of bias; and six had a moderate risk of bias due to not reporting randomization. β-TCP, when used as an ABG material, is biocompatible, visible, practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. Synthetic β-TCP for ABG can be an alternative to autologous bone grafts under certain terms and conditions. The efficacy of β-TCP for ABG in CL/P or alveolar bone cleft defects can be enhanced through a tissue engineering approach that combines β-TCP with growth factors, mesenchymal stem cells, or other graft materials, along with modifications to β-TCP's physical properties.
PubMed: 37886919
DOI: 10.3390/dj11100234