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International Journal of Molecular... Apr 2022Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with... (Meta-Analysis)
Meta-Analysis Review
The Use of Autologous Chondrocyte and Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects in Human Knee Joints-A Systematic Review and Meta-Analysis.
Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with significant functional and socioeconomic consequences. Implants consisting of autologous chondrocytes or mesenchymal stem cells (MSC) seeded onto scaffolds have been suggested as promising therapies to restore these defects. However, the degree of integration between the implant and native cartilage still requires optimization. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, CINAHL) to identify studies that used autologous chondrocyte implants (ACI) or MSC implant therapies to repair chondral defects of the tibiofemoral joint. Data on the integration of the implant-cartilage interface, as well as outcomes of clinical scoring systems, were extracted. Most eligible studies investigated the use of ACI only. Our meta-analysis showed that, across a total of 200 patients, 64% (95% CI (51%, 75%)) achieved complete integration with native cartilage. In addition, a pooled improvement in the mean MOCART integration score was observed during post-operative follow-up (standardized mean difference: 1.16; 95% CI (0.07, 2.24), = 0.04). All studies showed an improvement in the clinical scores. The use of a collagen-based scaffold was associated with better integration and clinical outcomes. This review demonstrated that cell-seeded scaffolds can achieve good quality integration in most patients, which improves over time and is associated with clinical improvements. A greater number of studies comparing these techniques to traditional cartilage repair methods, with more inclusion of MSC-seeded scaffolds, should allow for a standardized approach to cartilage regeneration to develop.
Topics: Cartilage Diseases; Cartilage, Articular; Chondrocytes; Humans; Knee Joint; Mesenchymal Stem Cells; Transplantation, Autologous
PubMed: 35409424
DOI: 10.3390/ijms23074065 -
The Open Orthopaedics Journal 2011Human adult mesenchymal stem cells (MSCs) were first identified by Friedenstein et al. when observing a group of cells that developed into fibroblastic colony forming...
Human adult mesenchymal stem cells (MSCs) were first identified by Friedenstein et al. when observing a group of cells that developed into fibroblastic colony forming cells (CFU-F). Ever since, the therapeutic uses and clinical applications of these cells have increased research and interest in this field. MSCs have the potential to be used in tissue engineering, gene therapy, transplants and tissue injuries. However, identifying these cells can be a challenge. Moreover, there are no articles bringing together and summarizing the cell surface markers of MSCs in adults. The purpose of this study is to summarize all the available information about the cell surface characterization of adult human MSCs by identifying and evaluating all the published literature in this field. We have found that the most commonly reported positive markers are CD105, CD90, CD44, CD73, CD29, CD13, CD34, CD146, CD106, CD54 and CD166. The most frequently reported negative markers are CD34, CD14, CD45, CD11b, CD49d, CD106, CD10 and CD31. A number of other cell surface markers including STRO-1, SH2, SH3, SH4, HLA-A, HLA-B, HLA-C, HLA-DR, HLA-I, DP, EMA, DQ (MHC Class II), CDIO5, Oct 4, Oct 4A, Nanog, Sox-2, TERT, Stat-3, fibroblast surface antigen, smooth muscle alpha-actin, vimentin, integrin subunits alpha4, alpha5, beta1, integrins alphavbeta3 and alphavbeta5 and ICAM-1 have also been reported. Nevertheless, there is great discrepancy and inconsistency concerning the information available on the cell surface profile of adult MSCs and we suggest that further research is needed in this field to overcome the problem.
PubMed: 21966340
DOI: 10.2174/1874325001105010253 -
International Journal of Molecular... Jan 2021Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations... (Meta-Analysis)
Meta-Analysis
Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords "nerve regeneration", "stem cells", "peripheral nerve injury", "rat", and "human" were used. Additionally, a "MeSH" research was performed in PubMed using the terms "stem cells" and "nerve regeneration". The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.
Topics: Animals; Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nerve Regeneration; Peripheral Nerves; Rats; Schwann Cells; Sciatic Nerve
PubMed: 33430035
DOI: 10.3390/ijms22020572 -
Stem Cell Reviews and Reports Dec 2020Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment...
BACKGROUND
Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN.
METHODS
A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool.
RESULTS
Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events.
CONCLUSION
The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting. Graphical abstract.
Topics: Animals; Disease Models, Animal; Humans; Male; Mandible; Mesenchymal Stem Cell Transplantation; Middle Aged; Osteoradionecrosis; Publication Bias; Risk; Time Factors; Wound Healing
PubMed: 32869179
DOI: 10.1007/s12015-020-10034-5 -
International Journal of Molecular... Jun 2024Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context,... (Review)
Review
Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.
Topics: Exosomes; Nerve Regeneration; Mesenchymal Stem Cells; Humans; Animals; Tissue Scaffolds; Peripheral Nerve Injuries; Mesenchymal Stem Cell Transplantation
PubMed: 38928194
DOI: 10.3390/ijms25126489 -
Medicina (Kaunas, Lithuania) Dec 2022Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures... (Meta-Analysis)
Meta-Analysis Review
Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle−Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10−37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17−6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.
Topics: Humans; Osteoarthritis, Knee; Fetal Blood; Mesenchymal Stem Cell Transplantation; Cartilage, Articular; Mesenchymal Stem Cells; Arthroscopy; Treatment Outcome
PubMed: 36557003
DOI: 10.3390/medicina58121801 -
Biomolecules Jan 2021Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as...
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as fistulas and cancer. Mesenchymal stem/stromal cells (MSCs) are being investigated as a novel therapy for IBD and have been demonstrated to be safe and effective for perianal fistulizing Crohn's disease (PFCD). This systematic review aims to present the most recent studies on the safety and efficacy of MSC therapy in IBD. A detailed search strategy of clinical trials on MSCs and IBD was performed on PubMed, with 32 studies selected for inclusion in this review. The newest studies on local MSC injection for PFCD continue to support long-term efficacy while maintaining a favorable safety profile. The evidence for systemic MSC infusion in luminal IBD remains mixed due to marked methodological heterogeneity and unclear safety profiles. Although further studies are needed to better establish the role of this novel treatment modality, MSCs are proving to be a very exciting addition to the limited therapies available for IBD.
Topics: Crohn Disease; Humans; Inflammatory Bowel Diseases; Injections; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 33440772
DOI: 10.3390/biom11010082 -
Regenerative Therapy Dec 2024Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs.... (Review)
Review
Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs. They can be caused by ischemic factors or hemorrhages, with ischemic strokes being the most common among the population. Therapies for patients suffering from this condition are limited and primarily focus on acute-phase treatment. In recent years, there has been an increase in cellular therapies, employing Stem Cells to mitigate or eliminate the consequences arising from this disease. Mesenchymal Stem Cells (MSCs) hold substantial therapeutic potential in Nervous System pathologies due to their low antigenicity and capacity to differentiate into various human tissues, such as adipogenic, chondrogenic, and osteogenic tissues. This study conducts a literature review using the "clinical trials" and "Pubmed" database, summarizing all ongoing clinical trials for ischemic strokes that utilize MSCs as treatment.
PubMed: 38633415
DOI: 10.1016/j.reth.2024.03.026 -
Stem Cells International 2021Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of... (Review)
Review
Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy to enhance bone regeneration. Growing evidence suggests that macrophages have a significant impact on osteogenesis during bone regeneration. However, the precise mechanisms by which macrophage subtypes influence bone regeneration and how MSCs communicate with macrophages have not yet been fully elucidated. In this systematic literature review, we gathered evidence regarding the crosstalk between MSCs and macrophages during bone regeneration. According to the PRISMA protocol, we extracted literature from PubMed and Embase databases by using "mesenchymal stem cells" and "macrophages" and "bone regeneration" as keywords. Thirty-three studies were selected for this review. MSCs isolated from both bone marrow and adipose tissue and both primary macrophages and macrophage cell lines were used in the selected studies. In conclusion, anti-inflammatory macrophages (M2) have significantly more potential to strengthen bone regeneration compared with naïve (M0) and classically activated macrophages (M1). Transplantation of MSCs induced M1-to-M2 transition and transformed the skeletal microenvironment to facilitate bone regeneration in bone fracture and bone defect models. This review highlights the complexity between MSCs and macrophages, providing more insight into the polarized macrophage behavior in this evolving field of osteoimmunology. The results may serve as a useful reference for definite success in MSC-based therapy based on the critical interaction with macrophages.
PubMed: 34221025
DOI: 10.1155/2021/8835156 -
Respiratory Research Oct 2019Inflammation plays an important role in the pathogenesis of many lung diseases. Preclinical studies suggest that mesenchymal stromal cell (MSC) conditioned media (CdM)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammation plays an important role in the pathogenesis of many lung diseases. Preclinical studies suggest that mesenchymal stromal cell (MSC) conditioned media (CdM) can attenuate inflammation. Our aim was threefold: (1) summarize the existing animal literature evaluating CdM as a therapeutic agent for pediatric/adult lung disease, (2) quantify the effects of CdM on inflammation, and (3) compare inflammatory effects of CdM to MSCs.
METHODS
Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed in five databases. Meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD).
RESULTS
A total of 10 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, and acute respiratory distress syndrome. CdM decreased inflammatory cells (1.02 SMD, 95% CI 0.86, 1.18) and cytokines (0.71 SMD, 95% CI 0.59, 0.84). The strongest effect for inflammatory cells was in bronchopulmonary dysplasia (3.74 SMD, 95% CI 3.13, 4.36) while pulmonary hypertension had the greatest reduction in inflammatory cytokine expression (1.44 SMD, 95% CI 1.18, 1.71). Overall, CdM and MSCs had similar anti-inflammatory effects.
CONCLUSIONS
In this meta-analysis of animal models recapitulating lung disease, CdM improved inflammation and had an effect size comparable to MSCs. While these findings are encouraging, the risk of bias and heterogeneity limited the strength of our findings.
Topics: Animals; Culture Media, Conditioned; Disease Models, Animal; Humans; Lung Diseases; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 31666086
DOI: 10.1186/s12931-019-1212-x