Progressive multiple sclerosis (PMS) is a disabling demyelinating disease characterized by irreversible neurodegeneration. Unlike relapsing-remitting MS, for which many disease-modifying therapies exist, treatment options for PMS are extremely limited. Only two agents (ocrelizumab and siponimod) have modest efficacy, and no effective therapies exist for non-active disease. Mesenchymal stem cell (MSC) transplantation has emerged as a promising strategy due to its immunomodulatory and neurotrophic properties. However, clinical trials have yielded inconsistent results, and prior meta-analyses were limited by mixed MS subtypes and non-randomized studies, leaving uncertainty about MSC's clinical utility in PMS.

Natural Killer cell kinetics and Killer-cell immunoglobulin-like receptors (KIRs) are increasingly recognized for their role during allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the prognostic impact of donor KIR haplotype configurations on patient survival remains controversial. To clarify this relationship, we conducted a systematic review and meta-analysis evaluating the impact of donor KIR haplotypes on the survival of patients undergoing allo-HSCT.

ST-segment elevation myocardial infarction (STEMI) remains a major cause of cardiovascular mortality and morbidity worldwide. Despite advances in reperfusion therapy, many patients still develop irreversible myocardial injury and adverse ventricular remodeling. Intracoronary mesenchymal stem cell (MSC) administration has been investigated as a potential therapeutic approach, but clinical evidence remains inconsistent. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intracoronary MSC administration with standard care in STEMI patients. Databases were searched from inception through February 2026. Eight RCTs involving 796 patients were identified, and seven trials with 400 patients were included in the quantitative analysis after excluding one study under Expression of Concern. MSC administration significantly improved ΔLVEF (I2 = 44.6%, p = 0.108; WMD = 3.18, 95% CI: 1.52-4.83, p < 0.001). No significant differences were detected in rehospitalization for heart failure (I2 = 0.0%, p = 0.592; RR = 1.14, 95% CI: 0.36-3.61, p = 0.831), all-cause mortality (I2 = 0.0%, p = 0.525; RR = 1.51, 95% CI: 0.24-9.31, p = 0.659), or MACE (I2 = 0.0%, p = 0.887; RR = 2.47, 95% CI: 0.55-11.05, p = 0.236). Intracoronary MSC administration after STEMI is associated with a modest improvement in left ventricular function, while no reduction in clinical events was found. No major safety signal was identified, although available safety data remain limited. Larger and well-designed trials with longer follow-up are still needed. Trial Registration: PROSPERO: CRD420261286620.

To compare the efficacy of current treatments for retinitis pigmentosa (RP)-associated macular oedema using network meta-analysis (NMA).

Alzheimer's disease (AD) is the leading cause of dementia, and effective disease-modifying therapies remain limited. Mesenchymal stem cells (MSCs) have shown therapeutic potential because of their neuroprotective and immunomodulatory properties, but clinical evidence remains inconclusive. We systematically evaluated the efficacy and safety of MSC therapy in AD. Following the PRISMA 2020 guidelines and a PROSPERO-registered protocol (CRD420261329891), we searched PubMed, the Cochrane Library, Embase, Web of Science, CNKI, and Wanfang from inception to March 1, 2026. Clinical studies of patients with primary AD treated with MSCs were included. Outcomes covered cognition, daily function, neuropsychiatric symptoms, biomarkers, imaging findings, and adverse events. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using R. Risk of bias was assessed with the RoB 2 tool, and evidence certainty was assessed with GRADE. Six studies involving 196 patients were included. Overall analyses showed no significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) or Mini-Mental State Examination (MMSE) at 12-16 weeks or 24-26 weeks after MSC treatment versus placebo, with substantial heterogeneity. Dose-stratified analyses suggested significant benefits of low-dose MSCs on ADAS-Cog (SMD = -1.33, 95% CI: -2.35 to -0.31) and MMSE (SMD = 2.59, 95% CI: 0.52-4.66). MSC therapy significantly improved Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; SMD = 3.27, 95% CI: 1.79-4.75), but not Neuropsychiatric Inventory (NPI) or Quality of Life in Alzheimer's Disease (QOL-AD) scale. Biomarker analyses showed no significant overall effects on Aβ42 or total tau, although subgroup analyses suggested possible increases in Aβ42 and reductions in total tau at certain doses. Imaging data from two studies indicated potential protective effects on hippocampal atrophy. MSC therapy was generally well-tolerated, although intracerebroventricular administration was associated with more transient adverse events. Evidence certainty was low to very low for most outcomes. MSC therapy for AD appears feasible and relatively safe, with potential cognitive and disease-modifying effects. However, current clinical evidence remains insufficient to confirm its efficacy.

Wound healing is a complex process of angiogenesis, inflammation and proliferation relying on co-ordination of multiple cell types and cytokines. Dysregulation of this process can lead to chronicity, which we are seeing more commonly due to an increasingly comorbid population. Adipose-Derived Stem Cells (ADSCs) show promise as a therapy though their ability to augment the tissue microenvironment via multiple pathways. This review aims to synthesise evidence on the effects of ADSCs on chronic wound healing to assess their efficacy. A systematic search of four databases was conducted covering a period up to June 2025. Comparative studies investigating ADSCs and wounds of any aetiology were included, and a meta-analysis was performed on pooled data. Ten studies were included in the meta-analysis (N = 498). Patients treated with ADSCs were more likely to heal at short-term follow-up (odds ratio (OR) 6.54, 95% confidence interval (CI) 3.80-11.27; n = 377 I2 = 0.00% p = 0.00) and healed significantly faster (mean difference -1.90, CI -2.28, -1.51; n = 210, I2 = 23.58, p = 0.00) than controls. Grades of recommendation, Assessment, Development and Evaluation assessment showed this evidence is of moderate certainty. This review presents clinical evidence that ADSC use is a safe therapy which expedites the healing of wounds from multiple aetiologies.

Background and objectives Stem cell therapy has emerged as a potential treatment for type 1 diabetes mellitus (T1DM), offering the possibility of modifying disease progression. This systematic review and meta-analysis aimed to assess the efficacy and safety of stem cell therapy in patients with T1DM. Methods We searched PubMed, Embase, Web of Science, and CENTRAL for randomised controlled trials (RCTs) published until January 2025 that evaluated stem cell therapy in T1DM. The primary outcome was the glycated haemoglobin (HbA1c) level. The secondary outcomes included fasting C-peptide levels, insulin dose reduction, insulin independence, and adverse events. The risk of bias was assessed using the Risk of Bias 2.0 tool. Results Eight reports from seven RCTs (169 participants) were included. Stem cell therapy was associated with a marginal reduction in HbA1c at 6 months [mean difference (MD): -0.57%, 95% CI: -1.13 to -0.02] but not at 12 months (-0.49%, -0.98 to 0.00). Fasting C-peptide levels (ng/mL) showed slight improvement at both 6 months (0.03, 0.03 to 0.03) and 12 months (0.09, 0.05 to 0.13). None of the participants achieved insulin independence or experienced serious adverse events. The certainty of the evidence was rated as very low for all outcomes. Interpretation and conclusions Stem cell therapy may offer marginal improvements in HbA1c and fasting C-peptide levels in T1DM; however, these benefits are of limited clinical significance. Given the small sample sizes, high heterogeneity, and very low certainty of evidence, well-designed, adequately powered RCTs are required to establish the therapeutic role of stem cells in T1DM.

Ischemic heart disease is a leading cause of morbidity and mortality. In this study, we assessed the efficacy of intracoronary stem cell transplantation on left ventricular function (LVEF) in acute myocardial infarction, chronic ischemic heart disease, and severe ischemic heart failure.   MATERIALS AND METHODS: We conducted a meta-analysis of randomized trials from 2002 to 2025. Mean difference in LVEF between treated and control patients at 6-months after infusion was calculated according to analysis of covariance. Heterogeneity among studies was assessed by the Cochrane's Q, Tau2, and I2 statistics. The primary outcome was the LVEF difference at follow-up. Secondary outcomes were comparisons among the type and number of transplanted stem cells.

Platelet-rich plasma (PRP) is widely used as an intra-articular treatment for knee osteoarthritis (KOA), but whether combining PRP with hyaluronic acid (HA), mesenchymal stem cells (MSCs), or ozone (O3) provides additional clinical benefit remains unclear. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of PRP monotherapy with these three PRP-based combination strategies.

This review aims to assess the effectiveness of epidural injections of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in treating chronic spinal pain. While existing literature has primarily concentrated on intradiscal regenerative therapies, this systematic review focuses specifically on the efficacy of PRP and MSCs when administered into the epidural space for managing chronic spinal pain.

Sjögren's syndrome (SjS) is a chronic autoimmune disease primarily characterized by xerostomia, often accompanied by xerophthalmia, cutaneous dryness, arthralgia, and stiffness. Mesenchymal stem cell (MSC)-based therapies have shown promising immunomodulatory potential in autoimmune diseases, yet their efficacy in SjS remains uncertain. Before advancing to clinical application, a systematic evaluation of preclinical evidence is essential to clarify their therapeutic impact and experimental consistency.

Neuroinflammatory and immune-mediated processes are increasingly recognized as important contributors to adult ischemic stroke pathobiology, contributing not only to acute neuronal injury and secondary tissue damage, but also to later phases of repair and recovery. Experimental and early clinical evidence suggests that immunotherapeutic interventions may modulate post-ischemic inflammatory cascades and immune-cell activation, thereby potentially contributing to neuroprotective and neurorestorative responses. However, the clinical efficacy, safety, and translational relevance of these approaches remain incompletely defined. This systematic review aimed to critically synthesize contemporary preclinical and clinical evidence on neuroinflammation-targeted immunotherapeutic strategies in adult ischemic stroke, while distinguishing direct immunotherapy from regenerative cell-based approaches with immunomodulatory relevance. A systematic search of PubMed/MEDLINE and Embase was conducted in October 2025 and updated in January 2026 to identify original English-language studies published between January 2020 and December 2025. Eligible studies included preclinical and clinical investigations evaluating direct immunotherapeutic interventions or regenerative cell-based therapies with immunomodulatory relevance in adult ischemic stroke, compared with placebo, standard care, or control conditions appropriate to study design. In total, 913 records were screened, of which 55 studies met all inclusion criteria and were included in the qualitative synthesis. Of these, three randomized controlled trials (N = 637) provided comparatively compatible, although methodologically heterogeneous, outcome data for an exploratory meta-analysis of excellent functional outcome at day 90. Methodological quality was assessed using validated design-specific tools for randomized controlled trials, observational studies, and preclinical animal experiments. Primary outcomes included functional recovery and infarct-related measures, while secondary outcomes encompassed neuroinflammatory biomarkers, immune modulation, and safety. Therapeutic approaches were categorized into molecular immunotherapy, biological immunotherapy, and regenerative cell-based therapies with immunomodulatory properties, according to their dominant mechanism of action and translational rationale. Molecular interventions targeting inflammatory and immunometabolic signaling pathways were associated with reductions in neuroinflammatory signaling and infarct-related measures in preclinical models in preclinical models, although corresponding human evidence remained limited. Regenerative cell-based therapies, including mesenchymal stromal/stem cells, progenitor cells, and related cellular products, demonstrated neuroregenerative, paracrine, and immunomodulatory characteristics in preclinical and early translational studies with favorable safety profiles; however, clinical functional benefits remained modest, heterogeneous, and inconsistent. Biological approaches, particularly monoclonal antibodies targeting leukocyte adhesion and immune-cell trafficking, demonstrated generally acceptable safety profiles but did not demonstrate consistent functional benefit across currently available randomized clinical trials. In the exploratory quantitative synthesis, no significant pooled clinical benefit was observed (OR = 0.87; 95% CI, 0.27-2.77), with moderate between-study heterogeneity (I2 = 46.3%). Cross-study comparability was further limited by substantial heterogeneity in intervention timing, dosing regimens, patient selection, biological targets, and outcome definitions, precluding definitive conclusions regarding efficacy. Neuroinflammation-targeted immunotherapy in adult ischemic stroke, together with selected regenerative cell-based strategies of immunomodulatory relevance, appears biologically plausible and mechanistically supported by current preclinical and early clinical evidence based on current preclinical and early clinical evidence and has demonstrated generally acceptable safety profiles in early-phase studies; however, current evidence remains insufficient to support consistent clinical benefit, and available trials may be insufficiently powered to reliably detect moderate but clinically meaningful treatment effects. Future research should prioritize mechanism-driven trial designs, standardized outcome measures, biomarker-informed patient stratification, optimized therapeutic windows, and integrative strategies combining immunomodulation with established reperfusion therapies. Well-powered, methodologically harmonized clinical trials aligned with the temporal and biological heterogeneity of post-stroke inflammation are essential to clarify translational potential and define the role of immune-targeted therapies in stroke management. Importantly, the present review supports a mechanistically differentiated framework in which direct immunotherapy and regenerative cell-based therapy should not be treated as interchangeable categories, even when both modulate post-stroke neuroinflammation. Overall, the available evidence may support further investigation of a stage-specific and mechanistically differentiated model of immune-targeted intervention in ischemic stroke.

Ischemia-reperfusion injury remains a critical determinant of graft outcomes in kidney transplantation, contributing to delayed graft function and reduced long-term survival. Machine perfusion has emerged as a dynamic preservation strategy offering a therapeutic window to condition organs prior to implantation. The integration of stem cells and extracellular vesicles (EVs), known for their immunomodulatory and cytoprotective properties, into perfusion protocols represents a novel and potentially synergistic approach. However, the evidence base remains limited and heterogeneous.

Mesenchymal stromal cells (MSCs) have the capacity to self-renew and exert immunomodulatory and paracrine effects. Our previously published systematic review of 55 randomized controlled trials (RCTs) of all MSC sources found an overall favorable safety profile for MSCs aside from more frequent fever in the MSC group.

To better characterize the genetic architecture underlying Alzheimer's disease (AD) and related dementias (ADRD), we performed a meta-analysis of European-ancestry genome-wide association studies in 128,681 cases or proxy cases of ADRD and 849,833 (proxy) controls. We identified 91 genetic loci associated with ADRD risk, of which 16 are new and 56 are specifically detected in clinically diagnosed AD cases. We also provide a list of 18 loci (15 new) requiring further external validation. A polygenic score combining the effects of ADRD loci other than APOE was primarily associated with AD rather than non-AD pathology. Individuals in the tenth decile of the score exhibited a twofold increased risk of presenting with Braak neurofibrillary tangles stage of >4 and moderate-to-severe neuritic amyloid plaque pathology at death compared to individuals in the median score group. In conclusion, our study validated a large number of loci associated with the risk of clinically diagnosed AD, while further investigations are required to confirm the impact of the other loci on AD clinical diagnosis and of each locus on AD pathology.

To systematically evaluate the effects of umbilical cord mesenchymal stem cells (UCMSCs) on the ovarian microenvironment in mouse models of premature ovarian failure (POF).

In recent years, the number of animal studies investigating mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy for osteochondral defects has steadily increased. However, a comprehensive and systematic quantitative analysis is lacking. This meta-analysis aimed to evaluate the efficacy of MSC-EVs in animal models of osteochondral defect through a meta-analysis.

Stem cell therapy holds considerable potential for treating dry eye syndrome, though it has yet to receive clinical approval.

Although the crosstalk between the immune system and tumour endothelial cells has been extensively investigated, interactions with tumour-associated pericytes (TAPs) remain poorly understood. Such issue may be of great interest considering the immunoregulatory roles of pericytes reported in both healthy and tumour tissues. This systematic review integrates current evidence on TAP-immune system interplay, encompassing functional roles, molecular mechanisms, associated biomarkers, and in vitro assessment methodologies. Preclinical investigations on the anticancer potential of TAP-targeted immunotherapies were also critically analysed, complemented by a meta-analysis assessing TAP-mediated immune regulation across distinct malignancies with a larger sample size.

Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are promising regenerative treatments for lumbar degenerative disc disease (DDD), but their comparative efficacy is unclear. This systematic review and indirect meta-analysis, conducted according to PRISMA guidelines and the PICOS framework, evaluated their effects on pain, function, and safety. PubMed, Scopus, and Web of Science were systematically searched, yielding 1694 records, of which 21 studies (nine randomized controlled trials [RCTs] and 12 prospective studies) were included. Data were analyzed qualitatively and quantitatively, and risk of bias was assessed using RoB 2 and ROBINS-I. Meta-analyses of randomized controlled trials (RCTs) examined pain and disability at 6 and 12 months using a random-effects model. Indirect comparisons were performed using the Bucher method. Qualitative synthesis showed that PRP consistently reduced pain (often > 50%) and improved function, frequently outperforming corticosteroids. MSCs provided sustained benefits, with follow-up extending up to 72 months in some studies. Quantitative meta-analysis of five RCTs demonstrated that PRP significantly reduced pain at 6 months (mean difference [MD] -16.4 mm) and disability (ODI -12.7), with effects persisting at 12 months in one study. In contrast, MSCs showed a modest but significant reduction in pain (MD -4.3 mm) and minimal functional improvement. Indirect comparisons favored PRP over MSCs at 6 months. Both treatments exhibited favorable safety profiles, with mostly mild and transient adverse events. Overall, PRP appears more effective than MSCs in the short to mid-term, although both therapies are safe. Further high-quality head-to-head RCTs are needed to confirm these findings and define optimal clinical indications.