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Spine Surgery and Related Research Sep 2022Considering the limitations of cell therapy, in case of adequate treatment efficacy, conditioned media (CM) may be a desirable alternative to cell therapy. Hence, the... (Review)
Review
BACKGROUND
Considering the limitations of cell therapy, in case of adequate treatment efficacy, conditioned media (CM) may be a desirable alternative to cell therapy. Hence, the present systematic review and meta-analysis aims to evaluate the efficacy of mesenchymal stem cell-derived conditioned media (MSC-CM) in movement resolution following spinal cord injury (SCI) in animal models.
METHODS
A comprehensive search in the databases of Medline, Scopus, Web of Science, and Embase was completed until the end of March 2021. Animal studies that evaluate the efficacy of MSC-CM on movement resolution following SCI were defined as the inclusion criteria. Lack of an SCI-untreated group, CM derived from a source other than MSC, not assessing motor function, failure to report CM administered dose, a follow-up period of less than 4 weeks, duplicates, and review articles were counted as the exclusion criteria. Final results are presented as overall standardized mean difference (SMD) with a 95% confidence interval (CI).
RESULTS
From the 361 nonduplicate articles, data from 11 articles were entered into the present meta-analysis. The analyses showed that MSC-CM administration in SCI animal models promotes motor recovery (SMD=2.32; 95% CI: 1.55, 3.09; p<0.0001). Subgroup analysis was performed because of the noticeable heterogeneity between the studies (I=80.97%, p<0.0001), depicting that antibiotic administration, delivery amount, delivery type, and follow-up time were the possible sources of heterogeneity. Moreover, multiple meta-regression demonstrated that in cases of delivery amount of more than 120 μL, the efficacy of MSC-CM administration in motor recovery is more than that of delivery amount of less than 120 μL (regression coefficient=3.30; 95% CI: 0.72, 5.89; p=0.019).
CONCLUSIONS
Based on the results of the present study, it can be concluded that MSC-CM administration in SCI models improves motor recovery. The efficacy of this treatment strategy significantly increases at doses higher than 120 μL.
PubMed: 36348669
DOI: 10.22603/ssrr.2022-0004 -
Stem Cells Translational Medicine Dec 2017Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most... (Meta-Analysis)
Meta-Analysis
Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM). Lung alveolarization was the primary outcome. We used random effects models for data analysis and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened 990 citations; 25 met inclusion criteria. All used hyperoxia-exposed neonatal rodents to model BPD. MSCs significantly improved alveolarization (Standardized mean difference of -1.330, 95% confidence interval [CI -1.724, -0.94, I 69%]), irrespective of timing of treatment, source, dose, or route of administration. MSCs also significantly ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis, and apoptosis. Similarly, MSC-CM significantly improved alveolarization, angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear risk of bias and incomplete reporting in the primary studies highlights nonadherence to reporting standards. Overall, safety and efficacy in other species/large animal models may provide useful information for guiding the design of clinical trials. Stem Cells Translational Medicine 2017;6:2079-2093.
Topics: Animals; Bronchopulmonary Dysplasia; Mesenchymal Stem Cell Transplantation; Rodentia
PubMed: 29045045
DOI: 10.1002/sctm.17-0126 -
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 -
BMC Oral Health Jul 2023Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present.
METHODS
The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence.
RESULTS
Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = - 1.18, 95% CI = - 1.55, - 0.80, P < 0.00001), pocket probing depth (PPD) (MD = - 0.75, 95% CI = - 1.35, - 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = - 0.95, 95% CI = - 1.67, - 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05).
CONCLUSION
The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high-quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.
Topics: Humans; Guided Tissue Regeneration, Periodontal; Alveolar Bone Loss; Periodontitis; Tooth Loss; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 37454056
DOI: 10.1186/s12903-023-03186-6 -
Cureus Aug 2023Mesenchymal stem cell (MSC) therapy is a frequently used treatment option for achieving a better prognosis in patients with heart failure (HF). However, due to reported... (Review)
Review
Mesenchymal stem cell (MSC) therapy is a frequently used treatment option for achieving a better prognosis in patients with heart failure (HF). However, due to reported adverse effects, patients are often hesitant to consider this treatment. Consequently, the aim of this systemic review and meta-analysis is to further investigate the effects of MSCs on survival outcomes, hospital readmissions, and left ventricular ejection fraction (LVEF) in individuals with pre-existing HF. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library to review studies published up until July 16, 2023. Risk ratios were generated using the extracted data for all the outcomes except LVEF. The mean difference was generated for LVEF. Sensitivity analysis was performed to investigate heterogeneity, and the risk of bias tool was used to assess the quality of the included studies. Fourteen randomized controlled trials were included in the meta-analysis. Pooled results revealed that the MSC therapy group did not significantly affect the outcomes of cardiovascular death, rehospitalization rate, myocardial infarction, recurrence of HF, and total death when compared to a control group. However, MSC therapy was significantly associated with an increased LVEF (RR = 3.35; 95% CI: 0.79-5.72; p = 0.010; I2 = 95%). Upon sensitivity analysis, MSC therapy was significantly associated with a decreased hospitalization rate (RR = 0.46; 95% CI: 0.34-0.64; p < 0.00001; I2 = 0%). MSC transplantation results in a significantly improved LVEF and rehospitalization rate.
PubMed: 37674948
DOI: 10.7759/cureus.43037 -
Oxidative Medicine and Cellular... 2018Based on animal studies, adult mesenchymal stromal cells (MSCs) are promising for the treatment of pancreatitis. However, the best type of this form of cell therapy and... (Review)
Review
BACKGROUND
Based on animal studies, adult mesenchymal stromal cells (MSCs) are promising for the treatment of pancreatitis. However, the best type of this form of cell therapy and its mechanism of action remain unclear.
METHODS
We searched the PubMed, Web of Science, Scopus, Google Scholar, and Clinical Trials.gov websites for studies using MSCs as a therapy for both acute and chronic pancreatitis published until September 2017.
RESULTS
We identified 276 publications; of these publications, 18 met our inclusion criteria. In animal studies, stem cell therapy was applied more frequently for acute pancreatitis than for chronic pancreatitis. No clinical trials were identified. MSC therapy ameliorated pancreatic inflammation in acute pancreatitis and pancreatic fibrosis in chronic pancreatitis. Bone marrow and umbilical cord MSCs were the most frequently administered cell types. Due to the substantial heterogeneity among the studies regarding the type, source, and dose of MSCs used, conducting a meta-analysis was not feasible to determine the best type of MSCs.
CONCLUSION
The available data were insufficient for determining the best type of MSCs for the treatment of acute or chronic pancreatitis; therefore, clinical trials investigating the use of MSCs as therapy for pancreatitis are not warranted.
Topics: Animals; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humans; Mesenchymal Stem Cells; Pancreatitis, Chronic
PubMed: 29743979
DOI: 10.1155/2018/3250864 -
Frontiers in Bioengineering and... 2022Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment...
Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy. The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis. 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group. The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed.
PubMed: 36588957
DOI: 10.3389/fbioe.2022.1006845 -
Systematic Reviews May 2022Stem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an autoimmune-based disorder, but previous studies have not presented a comprehensive view of its effect on treatment of T1DM.
METHODOLOGY
After registration of the present systematic review and meta-analysis in the PROSPERO, a search was done according to the Cochrane guidelines for evaluation of clinical trials to find eligible clinical trials that investigated the effect of SCT on T1DM (based on ADA® diagnostic criteria) from PubMed, Web of science, Scopus, etc, as well as registries of clinical trials from January 1, 2000, to September 31, 2019. A search strategy was designed using MeSH and EM-tree terms. Primary outcome included the changes in the insulin total daily dose (TDD) (U/kg) level, and secondary outcomes included the changes in the HbA1c, c-peptide, and adjusted HbA1c levels. The Q Cochrane test and I statistic were performed to assess the heterogeneity and its severity in primary clinical trials. The Cochrane ROB was used to determine risk of bias, and Cochrane Handbook for Systematic Reviews of Interventions was used in the full text papers. The meta-analysis was accomplished in the STATA software, and the results were shown on their forest plots. Confounders were evaluated by the meta-regression test.
RESULTS
A total of 9452 studies were electronically screened, and 35 papers were included for data extraction. The results of this review study showed that 173 (26.5%) diabetic patients experienced insulin-free period (from 1 to 80 months), and 445 (68%) showed reduction in TDD of insulin after the SCT. Combination of hematopoietic stem cell (HSC) with mesenchymal stem cell (MSC) transplantation were significantly associated with improvement of the TDD (SMD: - 0.586, 95% CI: - 1.204/- 0.509, I: 0%), HbA1c (SMD: - 0.736, 95% CI: - 1.107/- 0.365, I: 0%), adjusted HbA1c (SMD: - 2.041, 95% CI: - 2.648/- 1.434, I: 38.4%), and c-peptide (SMD: 1.917, 95% CI: 0.192/3.641, I: 92.5%) on month 3 of follow-up, while its association had a growing trend from 3 to 12 months after the transplantation. Considering severe adverse events, HSC transplantation accompanied with conditioning could not be suggested as a safe treatment.
CONCLUSION
Most of the clinical trials of SCT in T1DM were single arm. Although meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy.
RECOMMENDATION
Based on the results of this meta-analysis, the MSC and its combination with HSC could be considered as "Safe Cell" for SCT in T1DM. Furthermore, to evaluate the SCT efficacy, calculation of insulin TDD (U/kg/day), AUC of c-peptide, and adjusted HbA1c are highly recommended.
Topics: C-Peptide; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Hematopoietic Stem Cell Transplantation; Humans; Insulin; Mesenchymal Stem Cell Transplantation
PubMed: 35501872
DOI: 10.1186/s13643-022-01950-3 -
Frontiers in Cell and Developmental... 2021The skin is the largest organ of the human body, and its dysfunction is related to many diseases. There is a need to find new potential effective therapies for some skin... (Review)
Review
The skin is the largest organ of the human body, and its dysfunction is related to many diseases. There is a need to find new potential effective therapies for some skin conditions such as inflammatory diseases, wound healing, or hair restoration. Mesenchymal stromal cell (MSC)-conditioned medium (CM) provides a potential opportunity in the treatment of skin disease. Thus, the objective of this review is to evaluate the uses of MSC-CM for treating skin diseases in both animal and human models. A systematic review was conducted regarding the use of MSC-CM for treating skin conditions. One hundred one studies were analyzed. MSC-CM was evaluated in wound healing (55), hypertrophic scars (9), flap reperfusion (4), hair restoration (15), skin rejuvenation (15), and inflammatory skin diseases (3). MSC-CM was obtained from different MSC sources, mainly adipose tissue, bone marrow, and umbilical cord blood. MSC-CM was tested intravenously, intraperitoneally, subcutaneously, intradermally or intralesionally injected or topically applied. MSC-CM was used in both animals and humans. MSC-CM improved wound healing, hair restoration, skin rejuvenation, atopic dermatitis, and psoriasis in both animals and humans. MSC-CM also decreased hypertrophic scars and flap ischemia in animal models. In conclusion, MSC-CM is a promising therapy for skin conditions. Further studies are needed to corroborate safety and effectiveness and to standardize CM manufacturing.
PubMed: 34368115
DOI: 10.3389/fcell.2021.654210 -
Journal of Clinical Medicine Jun 2023The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the... (Review)
Review
BACKGROUND
The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach.
METHODS
We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction.
RESULTS
Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 10-1 × 10 mesenchymal stem cells, averaging 2.26 × 10. Most BMP-transduced MSC studies used lentivirus.
CONCLUSIONS
This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study.
PubMed: 37373757
DOI: 10.3390/jcm12124064