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Stem Cell Research & Therapy Jun 2024Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that MSC-based therapy is safe and effective in heart failure patients; however, its dose-response relationship has yet to be established. We aimed to determine the optimal MSC dose for treating HF patients with reduced ejection fraction (EF) (HFrEF).
METHODS
The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells).
RESULTS
MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment.
CONCLUSION
Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.
Topics: Humans; Heart Failure; Randomized Controlled Trials as Topic; Mesenchymal Stem Cell Transplantation; Stroke Volume; Mesenchymal Stem Cells; Ventricular Function, Left
PubMed: 38867306
DOI: 10.1186/s13287-024-03713-4 -
Gene Jun 2024The inhibition of dipeptidyl- peptidase 4 (DPP-4) is an essential therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of... (Review)
Review
The inhibition of dipeptidyl- peptidase 4 (DPP-4) is an essential therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of DPP-4 in cancer is not yet clear, with some studies suggesting that it may either promote or suppress tumors. This makes it crucial to have personalized treatment for diabetic women with cancer to effectively manage their diabetes whilst and preventing cancer mortality. To address this issue, we conducted an integrative in-silico analysis and systematic review of the literature to comprehensively examine the relationship between DPP-4 expression and the effects of its inhibitors on prevalent female malignancies. We specifically chose studies that examined the effects of DPP-4 expression and DPP-4 inhibition (DPP-4i) on prevalent cancers in women, such as breast cancer (BC), ovarian cancer (OV), cervical cancer (CC), and endometrial cancer (EC). These studies comprised those conducted both in vivo and in vitro. The review of the literature indicated that DPP-4i may worsen aggressive traits such as metastasis, Epithelial-to-mesenchymal transition (EMT), and chemotherapy resistance in BC cells. However, cohort studies on diabetic and BC patients did not confirm these findings. In vitro studies indicate that on OV, DPP-4 upregulation has been shown to prevent metastasis, while CCappears to be influenced by DPP-4 expression in terms of cell migration. sitagliptin, a pharmaceutical inhibitor of DPP-4, had a significant impact on reducing adhesion in CC cells in vitro. Overexpression of DPP-4 increased cell migration and proliferation in CC and EC cells, and hence the application of sitagliptin is expected to prevent this effect. On the other hand, the result of in-silico data confirmed that a significant correlation exists between DPP-4 expression and immune cell infiltration in breast, ovarian, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) as well as downregulated in these cancers compared to their normal tissue samples. Furthermore, a significant (p < 0.05) effect on OS of BC and CESC patients has been reported due to the elevation of DPP-4 methylation on a specific CPG Island. These findings could aid in creating specialized treatments for diabetic women with specific malignancies, but caution should be exercised when considering the patient's medical history and cancer type.
PubMed: 38866262
DOI: 10.1016/j.gene.2024.148659 -
Journal of Translational Medicine Jun 2024The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients.
METHODS
We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis.
RESULTS
A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation.
CONCLUSION
This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.
Topics: Humans; COVID-19; Mesenchymal Stem Cell Transplantation; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; Mesenchymal Stem Cells
PubMed: 38851730
DOI: 10.1186/s12967-024-05358-6 -
Journal of ISAKOS : Joint Disorders &... Jun 2024Orthobiologics has seen a renaissance over the last decade as an adjunct therapy during osteotomy due to the limited inherent regenerative potential of damaged... (Review)
Review
IMPORTANCE
Orthobiologics has seen a renaissance over the last decade as an adjunct therapy during osteotomy due to the limited inherent regenerative potential of damaged intraarticular tissues.
AIM OR OBJECTIVE
This systematic review aims to present the latest evidence regarding using orthobiologics with simultaneous high tibial osteotomy (HTO) for knee osteoarthritis. The results of this study may guide surgeons to improve their clinical results and clear the air regarding confusion over whether or not to add orthobiologics to HTO in clinical practice backed by scientific evidence.
EVIDENCE REVIEW
According to PRISMA guidelines a systematic search for relevant literature was performed in the PubMed (MEDLINE), Scopus, EMBASE, and Cochrane Library databases of all studies published in English from January 1990 to May 2023. The following search terms were entered into the title, abstract, and keyword fields: "knee" or "osteotomy" AND "valgus" or "varus" AND "regenerative medicine" or "PRP" or "mesenchymal stem cells" or "stem cells" or "BMAC" or "bone marrow" or "growth factors" or "umbilical cord blood-derived mesenchymal stem cell" or "stromal vascular fraction". The AMSTAR-2 checklist was used to confirm the quality of the systematic review. Randomised controlled trials (RCTs), prospective and retrospective comparative cohort studies, case-control studies, and case series were included. Studies that reported clinical outcomes in patients treated with knee osteotomy for varus/valgus knee with concomitant adjunction of regenerative treatment [Platelet-rich plasma (PRP), Adipose-derived stem cells (ADSC), Human Umbilical Cord Blood-Derived (HUCBD), Mesenchymal Stem Cells (MSC), bone marrow aspirate concentrate (BMAC), stromal vascular fraction (SVF)] were included. The outcome measures extracted from the studies were the KOOS score, Lysholm score, Subjective IKDC, WOMAC Score, KSS, Tegner, HSS, radiographic tibiofemoral angle, posterior tibial slope and complications. The current systematic review is registered in the PROSPERO Registry (CRD42023439379).
FINDINGS
Osteotomy for unicompartmental arthritis with adjunction of orthobiologics such as PRP, ADSC, HUCBD, MSC, BMAC, and SVF presents a consistent statistically significant clinical improvement compared to preoperative scores regardless of the treatment modality used and there were no notable complications associated with the use of these novel agents.
CONCLUSIONS AND RELEVANCE
Orthobiologics and knee osteotomies could improve outcomes in patients with knee osteoarthritis desiring Knee preservation surgeries. However, only a few studies are available on the topic to conclude anything with certainty, the patients included in the studies could not be disintegrated based on the grade of osteoarthritis (OA), type, dosage and frequency of administration of orthobiologic and type of additional surgical procedures used. Therefore, better-structured RCTs are required to implement this finding into routine Orthopaedic practice.
LEVEL OF EVIDENCE
Level 4.
PubMed: 38851324
DOI: 10.1016/j.jisako.2024.06.001 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
Research in Veterinary Science Aug 2024Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy... (Meta-Analysis)
Meta-Analysis Review
Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy requires different therapeutic goals. Mesenchymal stem cells (MSC) transplantation has spread over the years as a treatment for many diseases. In the urinary tract, studies report anti-inflammatory, antiapoptotic, antifibrotic, antioxidant and angiogenic effects. This work reports the results of a meta-analysis about the effects of the MSC application in serum levels of creatinine in dogs and cats with AKI and CKD. The work followed PRISMA guidelines. Data were screened, selected, and extracted with characteristics about the studies. The kinds of injury were classified according to their identification and the risk of bias was calculated by the system SYRCLE. The results of each group were combined by the inverse variance method. The heterogeneity was evaluated by the I test. For the mean of creatinine, a meta-analysis was performed according to the study group and number of applications and separately for the control and treatment groups according to the kind of injury, dose, application route, and moment. At all, 4742 articles were found. Of these, 40 were selected for eligibility, 16 underwent qualitative analysis and 9 to the quantitative. The results denote advantage to the group treated with MSC over placebo. A statistical difference was observed both in combined analysis and in the subgroups division. However, a high heterogeneity was found, which indicates considerable variation between the studies, which indicates caution in generalize the results.
Topics: Animals; Dogs; Mesenchymal Stem Cell Transplantation; Acute Kidney Injury; Cat Diseases; Cats; Dog Diseases; Renal Insufficiency, Chronic; Creatinine
PubMed: 38851051
DOI: 10.1016/j.rvsc.2024.105313 -
Multiple Sclerosis and Related Disorders Jul 2024Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS).
OBJECTIVE
This review delves into the literature on the efficacy and safety of MSC therapy for pwMS.
METHODS
A comprehensive search strategy was employed to identify relevant articles from five databases until January 2024. The inclusion criteria encompassed interventional studies. Efficacy and safety data concerning MSC therapy in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) groups were extracted and analyzed.
RESULTS
A comprehensive analysis encompassing 30 studies revealed that individuals who underwent intrathecal (IT) protocol-based transplantation of MSCs experienced a noteworthy improvement in their expanded disability status scale (EDSS) compared to the placebo group. Weighted mean difference (WMD) was -0.28; 95 % CI -0.53 to -0.03, I = 0 %, p-value = 0.028); however, the intravenous (IV) group did not show significant changes in EDSS scores. The annualized relapse rate (ARR) did not significantly decrease among pwMS (WMD = -0.34; 95 % CI -1.05 to 0.38, I = 98 %, p-value = 0.357). Favorable results were observed in magnetic resonance imaging (MRI), with only 19.11 % of pwMS showing contrast-enhanced lesions (CEL) in the short term and no long-term MRI activity. The most common complications in both short-term and long-term follow-ups were infection, back pain, and gastrointestinal symptoms.
CONCLUSIONS
The study highlights the safety potential of MSC therapy for pwMS. While MRI-based neural regeneration shows significant treatment potential, the effectiveness of MSC therapy remains uncertain due to study limitations and ineffective outcome measures. Further research is needed to establish efficacy and optimize evaluation methods for MSC therapy on pwMS.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Multiple Sclerosis; Outcome Assessment, Health Care; Multiple Sclerosis, Relapsing-Remitting
PubMed: 38838423
DOI: 10.1016/j.msard.2024.105681 -
Cureus May 2024In exploring therapeutic options for ischemic heart disease (IHD) and heart failure, cell-based cardiac repair has gained prominence. This systematic review delves into... (Review)
Review
In exploring therapeutic options for ischemic heart disease (IHD) and heart failure, cell-based cardiac repair has gained prominence. This systematic review delves into the current state of knowledge surrounding cell-based therapies for cardiac repair. Employing a comprehensive search across relevant databases, the study identifies 35 included studies with diverse cell types and methodologies. Encouragingly, these findings reveal the promise of cell-based therapies in cardiac repair, demonstrating significant enhancements in left ventricular ejection fraction (LVEF) across the studies. Mechanisms of action involve growth factors that stimulate angiogenesis, differentiation, and the survival of transplanted cells. Despite these positive outcomes, challenges persist, including low engraftment rates, limitations in cell differentiation, and variations in clinical reproducibility. The optimal dosage and frequency of cell administration remain subjects of debate, with potential benefits from repeated dosing. Additionally, the choice between autologous and allogeneic stem cell transplantation poses a critical decision. This systematic review underscores the potential of cell-based therapies for cardiac repair, bearing implications for innovative treatments in heart diseases. However, further research is imperative to optimize cell type selection, delivery techniques, and long-term efficacy, fostering a more comprehensive understanding of cell-based cardiac repair.
PubMed: 38832190
DOI: 10.7759/cureus.59474 -
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 Reviews and Reports May 2024Sepsis is a life-threatening disorder with no definitive cure. Preclinical studies suggest that extracellular vesicles derived from mesenchymal stromal cells (EV-MSCs)... (Review)
Review
BACKGROUND
Sepsis is a life-threatening disorder with no definitive cure. Preclinical studies suggest that extracellular vesicles derived from mesenchymal stromal cells (EV-MSCs) can mitigate inflammatory conditions, potentially leading to increased survival and reduced organ dysfunction during sepsis. Our aim to conduct this systematic review and meta-analysis is assessing the EV-MSCs therapeutic efficacy in sepsis.
METHODS
PubMed, Embase, Scopus, WOS and ProQuest databases and also Google Scholar search engine were searched for published articles. We used hazard ratio (HR) and standardized mean difference (SMD) as effect sizes to evaluate the therapeutic effect of EV-MSCs on survival rate and determine their effect on reducing organ dysfunction, respectively. Finally, we employed GRADE tool for preclinical animal studies to evaluate certainty of the evidence.
RESULTS
30 studies met the inclusion criteria for our article. Our meta-analysis results demonstrate that animals treated with MSC-EVs have better survival rate than untreated animals (HR = 0.33; 95% CI: 0.27-0.41). Our meta-analysis suggests that EV-MSCs can reduce organ dysfunctions in sepsis, such as the lung, kidney, and liver. Additionally, EV-MSCs decrease pro-inflammatory mediators like TNF-α, IL-1β, and IL-6.
CONCLUSION
Our results indicate that EV-MSCs can be as promising therapy for sepsis management in animal models and leading to increased survival rate and reduced organ dysfunction. Furthermore, our study introduces a novel tool for risk of bias assessment and provides recommendations based on various analysis. Future studies with aiming to guide clinical translation can utilize the results of this article to establish stronger evidence for EV-MSC effectiveness.
PubMed: 38814410
DOI: 10.1007/s12015-024-10741-3