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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 -
Therapeutic Advances in Respiratory... 2023In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the potential outburst of cytokine storm that damages the tissues and organs, especially the lungs. This leads to the manifestation of COVID-19 symptoms, such as pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and eventually death. Mesenchymal stromal/stem cells (MSCs) are currently one of hopeful approaches in treating COVID-19 considering its anti-inflammatory and immunomodulatory functions. On that account, the number of clinical trials concerning the use of MSCs for COVID-19 has been increasing. However, the number of systematic reviews and meta-analysis that specifically discuss its potential as treatment for the disease is still lacking. Therefore, this review will assess the safety and efficacy of MSC administration in COVID-19 patients.
OBJECTIVES
To pool evidence on the safety and efficacy of MSCs in treating COVID-19 by observing MSC-related adverse effects as well as evaluating its effects in reducing inflammatory response and improving pulmonary function.
DATA SOURCES AND METHODS
Following literature search across six databases and one trial register, full-text retrieval, and screening against eligibility criteria, only eight studies were included for data extraction. All eight studies evaluated the use of umbilical cord-derived mesenchymal stromal/stem cell (UC-MSC), infused intravenously. Of these eight studies, six studies were included in meta-analysis on the incidence of mortality, adverse events (AEs), and serious adverse events (SAEs), and the levels of C-reactive protein (CRP) and interleukin (IL)-6. Meta-analysis on pulmonary function was not performed due to insufficient data.
RESULTS
MSC-treated group showed significantly lower risk of mortality than the control group ( = 0.03). No statistical significance was observed on the incidence of AEs ( = 0.78) and SAEs ( = 0.44), and the levels of CRP ( = 0.06) and IL-6 ( = 0.09).
CONCLUSION
MSCs were safe for use, with lower risk of mortality and no association with AEs. Regarding efficacy, descriptive analysis showed indications of improvement on the inflammatory reaction, lung clearance, and oxygenation status despite the lack of statistical significance in meta-analysis of CRP and IL-6. Nevertheless, more studies are needed for affirmation.
REGISTRATION
This systematic review and meta-analysis was registered on the PROSPERO database (no. CRD42022307730).
Topics: Humans; COVID-19; SARS-CoV-2; Interleukin-6; Mesenchymal Stem Cell Transplantation; Cytokines; Mesenchymal Stem Cells
PubMed: 37128999
DOI: 10.1177/17534666231158276 -
Stem Cell Research & Therapy May 2023Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility, high proliferation rate, self-renewal and osteogenic differentiation capacity. Various organic and inorganic scaffold materials were pre-seeded with human dental pulp stem cells in animals, with promising outcomes in new bone formation. Nevertheless, the clinical trial for bone regeneration using dental pulp stem cells is still in its infancy. Thus, the aim of this systematic review and meta-analysis is to synthesise the evidence of the efficacy of human dental pulp stem cells and the scaffold combination for bone regeneration in animal bone defect models.
METHODOLOGY
This study was registered in PROSPERO (CRD2021274976), and PRISMA guideline was followed to include the relevant full-text papers using exclusion and inclusion criteria. Data were extracted for the systematic review. Quality assessment and the risk of bias were also carried out using the CAMARADES tool. Quantitative bone regeneration data of the experimental (scaffold + hDPSC/SHED) and the control (scaffold-only) groups were also extracted for meta-analysis.
RESULTS
Forty-nine papers were included for systematic review and only 27 of them were qualified for meta-analysis. 90% of the included papers were assessed as medium to low risk. In the meta-analysis, qualified studies were grouped by the unit of bone regeneration measurement. Overall, bone regeneration was significantly higher (p < 0.0001) in experimental group (scaffold + hDPSC/SHED) compared to the control group (scaffold-only) (SMD: 1.863, 95% CI 1.121-2.605). However, the effect is almost entirely driven by the % new bone formation group (SMD: 3.929, 95% CI 2.612-5.246) while % BV/TV (SMD: 2.693, 95% CI - 0.001-5.388) shows a marginal effect. Dogs and hydroxyapatite-containing scaffolds have the highest capacity in % new bone formation in response to human DPSC/SHED. The funnel plot exhibits no apparent asymmetry representing a lack of remarkable publication bias. Sensitivity analysis also indicated that the results generated in this meta-analysis are robust and reliable.
CONCLUSION
This is the first synthesised evidence showing that human DPSCs/SHED and scaffold combination enhanced bone regeneration highly significantly compared to the cell-free scaffold irrespective of scaffold type and animal species used. So, dental pulp stem cells could be a promising tool for treating various bone diseases, and more clinical trials need to be conducted to evaluate the effectiveness of dental pulp stem cell-based therapies.
Topics: Adult; Animals; Dogs; Humans; Bone Regeneration; Cell Differentiation; Dental Pulp; Osteogenesis; Stem Cell Transplantation; Tissue Scaffolds
PubMed: 37189187
DOI: 10.1186/s13287-023-03357-w -
International Journal of Molecular... Jul 2023Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and... (Review)
Review
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as "spinal cord injury," "stem cells," "stem cell therapy," "mesenchymal stem cells," and "traumatic spinal cord injury". Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Cell- and Tissue-Based Therapy; Myelin Sheath; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37511478
DOI: 10.3390/ijms241411719 -
Journal of Experimental Orthopaedics Oct 2023Mesenchymal stem cells (MSCs) present a valuable treatment option for knee osteoarthritis with promising results. The purpose of the present study was to systematically... (Review)
Review
PURPOSE
Mesenchymal stem cells (MSCs) present a valuable treatment option for knee osteoarthritis with promising results. The purpose of the present study was to systematically review the clinical and functional outcomes following mesenchymal stem cell application focusing on early to moderate knee osteoarthritis.
METHODS
A systematic search was done using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in Pubmed, Scopus, Web of Science, and Cochrane Library databases. All Studies published between 2017 and March 2023 on patients treated with single mesenchymal stem cell injection for Kellgren-Lawrence grade I-III knee osteoarthritis reported on clinical and functional outcomes were included.
RESULTS
Twelve articles comprising 539 patients and 576 knees treated with a single intraarticular injection of MSCs for knee osteoarthritis were included in the current systematic review. In eligible studies, the reported outcomes were improved concerning patient-reported outcomes measures, knee function, pain relief, and quality of patient's life.
CONCLUSION
Based on high-level evidence studies, single intraarticular injection of MSCs is a safe, reliable, and effective treatment option for Kellgren-Lawrence grade I-III knee osteoarthritis. However, the lack of homogeneity in the included studies and the variance in MSCs sources and preparations should be noted.
LEVEL OF EVIDENCE
III.
PubMed: 37804354
DOI: 10.1186/s40634-023-00665-1 -
Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
Frontiers in Immunology 2023During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery.
During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease (COVID-19) were explored. This study summarizes 195 clinical trials of advanced cell therapies targeting COVID-19 that were registered over the two years between January 2020 to December 2021. In addition, this work also analyzed the cell manufacturing and clinical delivery experience of 26 trials that published their outcomes by July 2022. Our demographic analysis found the highest number of cell therapy trials for COVID-19 was in United States, China, and Iran (N=53, 43, and 19, respectively), with the highest number per capita in Israel, Spain, Iran, Australia, and Sweden (N=0.641, 0.232, 0,223, 0.194, and 0.192 trials per million inhabitants). The leading cell types were multipotent mesenchymal stromal/stem cells (MSCs), natural killer (NK) cells, and mononuclear cells (MNCs), accounting for 72%, 9%, and 6% of the studies, respectively. There were 24 published clinical trials that reported on infusions of MSCs. A pooled analysis of these MSC studies found that MSCs provide a relative risk reduction for all-cause COVID-19 mortality of RR=0.63 (95% CI 0.46 to 0.85). This result corroborates previously published smaller meta-analyses, which suggested that MSC therapy demonstrated a clinical benefit for COVID-19 patients. The sources of the MSCs used in these studies and their manufacturing and clinical delivery methods were remarkably heterogeneous, with some predominance of perinatal tissue-derived products. Our results highlight the important role that cell therapy products may play as an adjunct therapy in the management of COVID-19 and its related complications, as well as the importance of controlling key manufacturing parameters to ensure comparability between studies. Thus, we support ongoing calls for a global registry of clinical studies with MSC products that could better link cell product manufacturing and delivery methods to clinical outcomes. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the near future, preventing pathology through vaccination still remains the best protection to date. We conducted a systematic review and meta-analysis of advanced cell therapy clinical trials as potential novel treatment for COVID-19 (resulting from SARS-CoV-2 coronavirus infection), including analysis of the global clinical trial landscape, published safety/efficacy outcomes (RR/OR), and details on cell product manufacturing and clinical delivery. This study had a 2-year observation interval from start of January 2020 to end of December 2021, including a follow-up period until end of July to identify published outcomes, which covers the most vivid period of clinical trial activity, and is also the longest observation period studied until today. In total, we identified 195 registered advanced cell therapy studies for COVID-19, employing 204 individual cell products. Leading registered trial activity was attributed to the USA, China, and Iran. Through the end of July 2022, 26 clinical trials were published, with 24 out of 26 articles employing intravenous infusions (IV) of mesenchymal stromal/stem cell (MSC) products. Most of the published trials were attributed to China and Iran. The cumulative results from the 24 published studies employing infusions of MSCs indicated an improved survival (RR=0.63 with 95% Confidence Interval 0.46 to 0.85). Our study is the most comprehensive systematic review and meta-analysis on cell therapy trials for COVID-19 conducted to date, clearly identifying the USA, China, and Iran as leading advanced cell therapy trial countries for COVID-19, with further strong contributions from Israel, Spain, Australia and Sweden. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the future, preventing pathology through vaccination remains the best protection.
Topics: Humans; COVID-19; SARS-CoV-2; RNA, Viral; Mesenchymal Stem Cell Transplantation; Spain
PubMed: 37415976
DOI: 10.3389/fimmu.2023.1200180 -
Journal of Clinical Medicine Sep 2023The assurance of safety and effectiveness is a significant focal point in all therapeutic approaches. Although mesenchymal stem cells (MSCs) have been identified as a... (Review)
Review
The assurance of safety and effectiveness is a significant focal point in all therapeutic approaches. Although mesenchymal stem cells (MSCs) have been identified as a potential novel therapeutic strategy for multiple sclerosis (MS), existing evidence regarding the effectiveness and safety of this strategy remains inconclusive. Thus, the primary aim of this systematic review and meta-analysis (SRMA) was to comprehensively assess the effectiveness and safety of MSC therapy in individuals diagnosed with MS. A comprehensive search was conducted using appropriate keywords in the PubMed, Scopus, Cochrane, ScienceDirect, and Google Scholar databases to determine the eligible studies. The change in the expanded disability status scale (EDSS) score from baseline to follow-up was used to assess MSC efficacy. The effectiveness of the therapy was assessed using a random-effects model, which calculated the combined prevalence and 95% confidence intervals (CIs) for MS patients who experienced improvement, stability, or worsening of their condition. The protocol was registered in PROSPERO (CRD42020209671). The findings indicate that 40.4% (95% CI: 30.6-50.2) of MS patients exhibited improvements following MSC therapy, 32.8% (95% CI: 25.5-40.1) remained stable, and 18.1% (95% CI: 12.0-24.2) experienced a worsening of their condition. Although no major complications were observed, headaches 57.6 [37.9-77.3] and fever 53.1 [20.7-85.4] were commonly reported as minor adverse events. All of the results reported in this meta-analysis are consistent and credible according to the sensitivity analyses. Regardless of different individual studies, our meta-analysis provides a comprehensive overview showing the potential of MSC therapy as a possible effective treatment strategy for patients with MS.
PubMed: 37834955
DOI: 10.3390/jcm12196311 -
PloS One 2023Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques.
METHODS AND FINDING
A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration.
CONCLUSION
This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Treatment Outcome; Controlled Clinical Trials as Topic
PubMed: 37498842
DOI: 10.1371/journal.pone.0284828 -
BioMed Research International 2022The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of... (Review)
Review
BACKGROUND
The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19.
METHODS
A systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. . After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. . We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.
Topics: COVID-19; Exosomes; Humans; Mesenchymal Stem Cells; Prospective Studies; Pulmonary Fibrosis
PubMed: 35782071
DOI: 10.1155/2022/9346939