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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 -
International Journal of Molecular... May 2023Back pain is the single leading cause of disability worldwide. Despite the prevalence and morbidity of lower back pain, we still lack a gold-standard treatment that... (Review)
Review
Back pain is the single leading cause of disability worldwide. Despite the prevalence and morbidity of lower back pain, we still lack a gold-standard treatment that restores the physiological function of degenerated intervertebral discs. Recently, stem cells have emerged as a promising strategy for regenerative therapy for degenerative disc disease. In this study, we review the etiology, pathogenesis, and developing treatment strategies for disc degeneration in low back pain with a focus on regenerative stem cell therapies. A systematic search of PubMed/MEDLINE/Embase/Clinical Trials.gov databases was conducted for all human subject abstracts or studies. There was a total of 10 abstracts and 11 clinical studies (1 RCT) that met the inclusion criteria. The molecular mechanism, approach, and progress of the different stem cell strategies in all studies are discussed, including allogenic bone marrow, allogenic discogenic cells, autologous bone marrow, adipose mesenchymal stem cells (MSCs), human umbilical cord MSC, adult juvenile chondrocytes, autologous disc derived chondrocytes, and withdrawn studies. Clinical success with animal model studies is promising; however, the clinical outcomes of stem cell regenerative therapy remain poorly understood. In this systematic review, we found no evidence to support its use in humans. Further studies on efficacy, safety, and optimal patient selection will establish whether this becomes a viable, non-invasive therapeutic option for back pain.
Topics: Adult; Animals; Humans; Low Back Pain; Intervertebral Disc Degeneration; Mesenchymal Stem Cell Transplantation; Back Pain; Intervertebral Disc
PubMed: 37240236
DOI: 10.3390/ijms24108893 -
Systematic review of preclinical and clinical studies on scaffold use in knee ligament regeneration.Current Stem Cell Research & Therapy 2015The management and treatment of ligamentous injuries within an orthopaedic population has continued to evolve throughout the last several decades. Limitations with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The management and treatment of ligamentous injuries within an orthopaedic population has continued to evolve throughout the last several decades. Limitations with autograft, allograft and synthetics have led to research into tissue engineering using scaffolds and mesenchymal stem cells.
OBJECTIVES
This systematic review aims to examine and summarise the pre clinical in-vivo studies and limited clinical studies on the use of scaffolds in the treatment of ligamentous injuries Data sources:
DATABASES
PubMed, CINAHL, Web of science, Medline, Cochrane library and Embase. The following key words and search terms were used: scaffolds, ligament, mesenchymal stem cells, tissue engineering, clinical, and preclinical.
METHODS
A total of 118 articles were reviewed. 19 articles were identified as relevant for the purpose of this systematic literature review. An additional 2 articles were sourced from the reference list of reviewed articles.
RESULTS
Three tables of studies were constructed: pre clinical biological scaffolds, pre clinical synthetic scaffolds and clinical scaffolds.
CONCLUSIONS
There is a large body of pre clinical evidence that the use of scaffolds combined with mesenchymal stem cells can be a viable option in the regeneration of ligamentous structures with biological and mechanical properties suitable for function. There is, however, limited clinical evidence supporting the use of recently developed scaffolds and historical evidence of synthetic scaffolds failing in the management of anterior cruciate ligament repairs. There appears to be no consensus in the literature as to the nature of the scaffold material that is most suitable for clinical trials. No randomised control trials have yet been conducted.
Topics: Animals; Clinical Trials as Topic; Humans; Knee; Ligaments; Mesenchymal Stem Cells; Regeneration; Tissue Engineering; Tissue Scaffolds
PubMed: 25012742
DOI: 10.2174/1574888x09666140710101435 -
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 -
Heart, Lung & Circulation Jul 2023Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most well-studied and characterised stem cell types. This review was undertaken of the current available... (Meta-Analysis)
Meta-Analysis Review
AIM
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most well-studied and characterised stem cell types. This review was undertaken of the current available phase II/III randomised clinical trials (RCTs) that delivered BM-MSCs to treat patients with cardiomyopathy, and to assess their performance.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed during the systematic review and meta-analysis. Eligible studies were reviewed, and their data charted. To assess the efficacy of BM-MSCs, the outcome was improvement in left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD).
RESULTS
The pooled weighted mean difference (WMD) showed that BM-MSCs treatment improved the 6MWD by 27.86 m (95% CI 0.11-55.6 m) compared with the control groups. The pooled WMD showed that BM-MSCs treatment improved the LVEF by 6.37% (95% CI 5.48%-7.26%) compared with the control groups.
CONCLUSION
BM-MSCs treatment is an effective intervention for managing patients with heart failure, but it requires larger and more robust clinical trials to support its routine use in clinics.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Heart Failure; Cardiomyopathies; Mesenchymal Stem Cells; Ventricular Function, Left; Bone Marrow Cells
PubMed: 36872163
DOI: 10.1016/j.hlc.2023.01.012 -
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 -
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 -
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 -
Epilepsia Jul 2022Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and... (Review)
Review
Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.
Topics: Animals; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 35451066
DOI: 10.1111/epi.17266 -
Cureus Dec 2022Bronchopulmonary dysplasia (BPD) is a frequent sequela of modern medicine when infants are born prematurely. Currently, there is no single treatment or combination of... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a frequent sequela of modern medicine when infants are born prematurely. Currently, there is no single treatment or combination of treatments to prevent or fully treat BPD. Mesenchymal stem cells (MSCs) have promising properties that could aid in the reversal of lung injury, as seen in patients with BPD. This study reviews the available evidence regarding the safety and efficacy of the use of MSCs for the treatment of evolving and established BPD. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We found eight studies that fulfilled the inclusion and exclusion criteria. While all studies proved the safety and efficacy of MSCs administered intravenously and intratracheally, the only available randomized controlled trial (RCT) failed to demonstrate the benefit of MSC administration in the early treatment of BPD. The remaining studies varied between phase I clinical trials and case reports, but all seemed to show some evidence that MSCs may be of benefit in the late treatment of established BPD. Considering some of the studies have less evidence, early treatment to prevent lung fibrosis may be more successful, particularly in the younger gestational ages where lung development is more immature, and research should focus on this.
PubMed: 36660501
DOI: 10.7759/cureus.32598