Leukemia stem cells (LSC) are thought to be responsible for relapse in patient with acute myeloid leukemia (AML). LSC can be quantified at diagnosis to improve risk stratification, and during follow-up to monitor residual disease. To systematically evaluate the prognostic relevance of measuring LSC at diagnosis and in remission in patients with AML, we conducted a systematic and reconstructed individual patient data meta-analysis. We performed a comprehensive search for studies that reported overall survival (OS) and/or event-free survival (EFS) in relation to LSC measurements at diagnosis or in remission. We reconstructed individual patient data based on Kaplan Meier curves. Fifty-six studies were included, including a total of 44 cohorts (n=7781) for OS and 37 cohorts (n=5032) for EFS at diagnosis, and 19 cohorts (n=2006) for OS and 22 cohorts (n=1342) for EFS in remission. Positive LSC status was significantly associated with inferior OS and EFS at diagnosis (OS: hazard ratio [HR] 1.96 (1.85-2.08); EFS: HR 2.32 (2.15-2.49)) and in remission (OS: HR 2.59 (2.23-3.03); EFS: HR 2.53 (2.18-2.94)). To conclude, we found that measuring LSC has prognostic relevance both at diagnosis and in remission. This supports LSC frequency as a key prognostic factor that warrants implementation into clinical practice.

Despite currently available treatment options for moderate-to-severe atopic dermatitis (AD), some patients fail to achieve adequate disease control. Emerging evidence suggests that mesenchymal stem cells (MSCs) may represent a promising therapeutic option. This systematic review and meta-analysis included four randomized controlled trials (RCTs) and one non-randomized clinical trial. Eligible studies evaluated patients with moderate-to-severe AD treated with MSCs derived from human umbilical cord blood, autologous adipose tissue, and allogeneic bone marrow. PubMed, Embase, and Cochrane were searched from inception to December 2025. Primary outcomes included the proportion of patients achieving ≥50% and ≥75% improvement from baseline in the Eczema Area and Severity Index (EASI) and safety outcomes. The meta-analysis included 236 participants. The pooled EASI-50 response rate at week 12 was 46.76% (95% confidence interval [CI]: 32.36% to 61.72%). EASI-75 response rates were 17.41% (95% CI: 5.56% to 43.03%) at week 12 and 23.97% (95% CI: 16.48% to 33.50%) at week 16. The pooled incidence of treatment-emergent adverse events was 26.86% (95% CI: 19.56% to 35.68%), with infections and infestations 7.97% (95% CI: 4.11% to 14.88%) and gastrointestinal disorders 3.52% (95% CI: 1.33% to 9.01%) being the most frequently reported. MSC-based therapy shows early promise as a potential treatment for moderate-to-severe AD, offering a possible alternative to traditional therapies. However, the current evidence is largely based on small clinical trials, underscoring the necessity for large-scale RCTs to establish the efficacy and safety of MSC-based therapy in broader patient populations.

The primary aim of this review is to summarize current evidence from clinical and pre-clinical studies on endogenous molecular biomarkers associated with radiosensitivity and radioresistance in cervical cancer, including patients treated with photon-based radiotherapy, cervical cancer cell lines, and xenograft models, and to evaluate the association of these biomarkers with radiotherapy response, residual disease, recurrence and survival, and experimental measures of radiosensitivity. A systematic literature review was conducted for studies published over the last 10 years that evaluated associations between genomic, epigenetic, or protein biomarkers and radiotherapy response or survival outcomes in cervical cancer. Eligible studies included in the current analysis summarize clinical, translational, and pre-clinical studies in correlation with photon-based radiotherapy. Research focusing exclusively on non-coding RNAs, exogenous radiosensitizers, or non-photon modalities was excluded. In total, 112 studies were identified, and 46 of them met the inclusion criteria. The identified biomarkers clustered into several key biological processes: DNA damage response and cell cycle regulation, cancer stemness, hypoxia and microenvironment, epigenetic and transcriptional regulation, and signaling pathways, including exosome-mediated communication. Most markers were linked to radioresistance and adverse outcomes, whereas a smaller subset was associated with increased radiosensitivity. A limited group of biomarkers was linked to clinical outcomes such as local control, residual disease, or survival, and emerging multi-marker protein signatures suggested that combinatorial approaches may outperform single-marker strategies. Radiosensitivity in cervical cancer is regulated by a network of biological pathways. Validated, integrated biomarker panels that capture DNA repair proficiency, stemness, hypoxia adaptation, and key signaling pathways are needed to improve risk stratification and enable biomarker-guided radiosensitization.

Despite improved outcomes with antiretroviral therapy, HIV-associated lymphoma (HAL) remains a major cause of mortality. Autologous stem cell transplant (ASCT) may be curative for relapsed/refractory (R/R) HAL, but HIV-related immunosuppression complicates management. We systematically reviewed prospective evidence on ASCT efficacy and toxicity in HAL.

To systematically review randomized controlled trials and quantitatively evaluate the efficacy and safety of injections of autologous adipose-derived mesenchymal stromal cells (AD-MSCs) in patients with knee osteoarthritis (OA).

Corneal blindness remains a major global health burden, limited by donor shortage and graft-related complications. Tissue-engineered corneal substitutes have emerged as a promising alternative, aiming to restore corneal structure and function through bioengineered constructs.

This systematic review and meta-analysis aimed to evaluate the effectiveness of stem cell therapies for patients with amyotrophic lateral sclerosis (ALS) based on optimal dosing and administration routes, as well as the safety profiles of stem cells and their derived products.

Rotator cuff tears are common in older adults, leading to significant pain and limitations. Despite advances in arthroscopic repair, high re-tear rates, especially in large tears, remain a challenge. This review examines biomaterial patches in rotator cuff repair, focusing on mechanisms that support tendon healing and lower re-tear rates.

Knee osteoarthritis (OA) is a common degenerative joint condition for which current treatments primarily provide symptom control without restoring cartilage. Biologic injectables such as platelet-rich plasma (PRP) and adipose-derived cellular preparations have gained interest as potential disease-modifying options. This review compares the current clinical evidence regarding their relative effectiveness.

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.

Kidney disease is a major global health burden with limited regenerative treatment options. Induced pluripotent stem cells (iPSCs) offer patient-specific pluripotency and the potential to generate renal cells and organoids, making them a promising approach for kidney repair.

Oral squamous cell carcinoma (OSSC) remains highly lethal, with resistance largely driven by cancer stem cells (CSCs). Mitochondrial reprogramming supports CSC redox control, self-renewal, and survival. This systematic review aimed to synthesize mitochondrial mechanisms sustaining CSCs in OSCC and evaluate their therapeutic relevance.

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.

The COVID-19 pandemic created a unique situation in which researchers repurposed human models of varying complexity to investigate SARS-CoV-2, providing the opportunity to analyse their contribution across organs.

Chronic and complex skin wounds, including diabetic ulcers and burns, represent a major clinical challenge with substantial morbidity and healthcare costs. Regenerative approaches have evolved from stem cell-based therapies toward stem cell-free strategies, particularly mesenchymal stroma/stem cell-derived extracellular vesicles (MSC-EVs). However, the relative strength, consistency, and translational readiness of these approaches remain unclear. The aim of this study is to synthesize and critically appraise evidence from systematic reviews and meta-analyses on cell-based and cell-free regenerative therapies for wound healing, with emphasis on clinical relevance, methodological quality, and recent developments. An umbrella review was conducted in accordance with PRISMA 2020 guidance. PubMed/MEDLINE, Scopus, and Web of Science were searched for systematic reviews and meta-analyses published in English within the last 5 years. Eligible reviews evaluated cell-based therapies and/or extracellular vesicle-based interventions for skin wound healing in clinical and/or animal models. Methodological quality was assessed using AMSTAR-2, and overlap of primary studies was evaluated using the corrected covered area (CCA). Seven systematic reviews and meta-analyses were included, encompassing both clinical and preclinical evidence. Notably, the majority of included evidence was derived from diabetic wound models, particularly in preclinical animal studies. Cell-based therapies demonstrated clinically relevant benefits in specific settings, such as autologous skin cell suspensions for burns and biologic skin substitutes for diabetic foot ulcers, although certainty of evidence was low to moderate. In contrast, MSC-EVs showed large and consistent effects on wound closure, angiogenesis, collagen deposition, and inflammatory modulation in preclinical models. No randomized human trials of EV-based wound therapies were identified. Current evidence suggests a paradigm shift toward stem cell-free regenerative strategies in wound healing. While cell therapies have limited but established clinical roles, MSC-EVs offer strong preclinical efficacy and translational potential. Standardization, regulatory alignment, and well-designed clinical trials are required to enable safe clinical implementation.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus and obesity, have recently attracted attention for their potential effects on periodontal tissues. This systematic review aimed to evaluate the current evidence regarding the relationship between GLP-1-based therapies and periodontal health, with particular emphasis on anti-inflammatory, osteogenic, and regenerative mechanisms. A comprehensive literature search of PubMed, Web of Science, and Embase databases identified 22 eligible studies, including in vitro, animal, and human investigations. The available evidence suggests that GLP-1RAs such as liraglutide and exendin-4 may attenuate periodontal inflammation, reduce alveolar bone loss, and enhance osteogenic differentiation of periodontal ligament and dental pulp stem cells through modulation of pathways including MAPK/ERK, Wnt/β-catenin, NF-κB, and PKCβ2. Clinical observations additionally indicate a bidirectional relationship between periodontitis and incretin signalling, with periodontal therapy associated with increased systemic GLP-1 levels. However, the current evidence remains heterogeneous and is largely limited to preclinical and observational studies. Randomised clinical trials are required to determine the clinical efficacy and therapeutic relevance of GLP-1-based therapies in periodontitis management.

Colorectal cancer stem cells (CRC-SCs) contribute to treatment resistance, tumor recurrence and disease progression. Despite therapeutic advances, CRC-SCs frequently evade eradication and sustain tumor propagation. Although multiple molecular pathways have been implicated in this resistance, current preclinical evidence remains fragmented. This systematic review aims to synthesize preclinical evidence on the molecular mechanisms underlying CRC-SC resistance to modern anticancer therapies. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted to identify peer-reviewed original studies published between 2015 and 2025. Eligible studies investigated molecular mechanisms of CRC-SC resistance to chemotherapy, targeted therapy, immunotherapy, and other therapeutic modalities. Risk of bias was assessed using QUIN for in vitro studies and SYRCLE for in vivo studies. A total of 26 studies met the inclusion criteria. Synthesis of findings showed that CRC-SC resistance is driven by interconnected mechanisms, including adaptive signaling pathways, epigenetic reprogramming, enhanced DNA damage response, and protective interactions within the tumor microenvironment. Several studies reported that combination treatments targeting these mechanisms attenuated stemness characteristics and restored therapeutic sensitivity. Overall, CRC-SC resistance arises from multiple intrinsic and extrinsic mechanisms, supporting further preclinical and translational evaluation of combination strategies.

Background: Ankle osteoarthritis (OA) differs fundamentally from knee OA: it is predominantly post-traumatic, affects younger and more active patients, and frequently arises from focal osteochondral lesions of the talus (OCLT) rather than diffuse degeneration. Cell-based and orthobiologic therapies-bone marrow aspirate concentrate (BMAC), bone marrow-derived cell transplantation (BMDC), adipose-derived mesenchymal stromal cells (ADMSCs), stromal vascular fraction (SVF), micro-fragmented adipose tissue (mFAT), and peripheral blood-derived products-have been proposed as joint-preserving options, but the evidence base has not been mapped in a way that separates degenerative post-traumatic ankle OA from focal chondral repair, or that distinguishes cells given as a standalone injection from cells given alongside a therapeutic operation. Methods: We conducted a systematic scoping review following the PRISMA-ScR framework. Human clinical studies applying cell-based therapies to post-traumatic ankle OA and/or OCLT were charted by population, cell source and preparation, mode of delivery, concomitant procedures, follow-up, and reported clinical and structural outcomes. Mode of delivery-standalone intra-articular injection versus adjunct to a concomitant surgical procedure-was pre-specified as a primary analytic axis, because it determines whether an observed effect can be attributed to the cell product at all. Given anticipated clinical and product heterogeneity and the near-absence of controlled trials of standalone injection, no meta-analysis was undertaken; the objective was to map the evidence, characterise its structure, and identify gaps. Results: Eleven clinical studies were charted. The dominant structural feature of this literature is that in nine of 11 studies the cells were co-administered with a therapeutic surgical procedure-marrow stimulation, autologous osteochondral transplantation, supramalleolar or calcaneal osteotomy, or joint debridement-so that in no charted study can the contribution of the cells be separated from that of the operation. This attribution problem, rather than any efficacy estimate, is the principal finding of the review. The remaining evidence is small, heterogeneous, and uniformly non-randomised (Level of Evidence III-V). Only two studies used standalone injection, and for degenerative post-traumatic ankle OA specifically, the standalone-injection evidence consists of a single case report. Reported clinical outcomes (AOFAS, VAS, FAOS/KOOS, Tegner) and structural surrogates (MOCART, T2-mapping, second-look arthroscopy) were generally favourable, and adverse events were mild and self-limiting; however, no study demonstrated histologically confirmed hyaline regeneration, and no adequately powered randomised trial of standalone injection for degenerative post-traumatic ankle OA was identified. Conclusions: Cell-based therapies for post-traumatic ankle OA and OCLT show promising but preliminary, hypothesis-generating signals within a fragmented evidence base in which the cellular contribution is confounded by concomitant surgery in nine of 11 charted studies; on present evidence, the field cannot claim an independent effect for the cell product. The knee OA evidence cannot be extrapolated to the ankle because of the joint's distinct biology, aetiology, and lesion pattern. Adequately powered randomised trials of standalone intra-articular injection in well-defined degenerative post-traumatic ankle OA, using standardised product characterisation and a core outcome set with quantitative structural endpoints, are the principal advance needed.

Background: Intra-articular (IA) stem cell injection is an emerging treatment for knee osteoarthritis (KOA). Three principal cell sources-adipose-derived mesenchymal stem cells (ADMSCs), bone marrow-derived MSCs (BMMSCs), and peripheral blood-derived stem cells (PBSCs)-have been evaluated independently; however, a systematic review comprehensively comparing all three sources under unified eligibility criteria is absent from the literature. Methods: Systematic searches of MEDLINE, Embase, Cochrane CENTRAL, and Scopus were conducted from inception to December 2025, supplemented by manual reference screening and ClinicalTrials.gov. Eligible studies included randomized controlled trials (RCTs) and prospective comparative studies in adult KOA patients. Primary outcomes were pain (VAS/NRS) and function (WOMAC, KOOS) at ≥3 months. Risk of bias was assessed using RoB 2 and ROBINS-I; evidence certainty was rated using GRADE. Results: Thirty-one studies (n = 1247; ADMSC: 14 studies, n = 612; BMMSC: 12 studies, n = 487; PBSC: 5 studies, n = 148) met inclusion criteria. Pooled standardized mean differences (SMDs) for 6-month pain showed significant reduction versus comparators for ADMSCs (SMD -1.23; 95% CI -1.61 to -0.85; I2 = 62%) and BMMSCs (SMD -1.09; 95% CI -1.55 to -0.63; I2 = 70%). PBSCs demonstrated significant within-group improvement but were too few for formal pooling. Because no trial compared cell sources head-to-head, these estimates reflect within-source efficacy versus each study's own comparator rather than comparative superiority between sources. Adverse events were mild and transient across all sources. GRADE certainty was moderate for ADMSCs, low for BMMSCs, and very low for PBSCs. Conclusions: IA injection of ADMSCs and BMMSCs provides pain reduction and functional improvement in KOA with point estimates reaching minimal clinically important difference thresholds, although the certainty of this evidence is only moderate (ADMSC) to low (BMMSC). PBSC evidence is insufficient for formal comparison. Adequately powered, three-arm head-to-head RCTs that share a common comparator and a core outcome set are needed to establish comparative efficacy. Because only indirect comparisons were possible, this review supports efficacy within each cell source but cannot establish the superiority of one source over another.

Right-hemisphere gliomas have traditionally been regarded as less eloquent than left-sided lesions, influencing surgical decision-making and anesthetic approach. However, these tumors produce diverse non-motor manifestations affecting cognition, behavior, and socio-emotional functioning with important consequences for quality of life. This review aimed to characterize these manifestations and their implications for functional eloquence.