Oral potentially malignant disorders (OPMDs) have varying risk of malignant transformation (MT), yet the underlying mechanisms remain unclear. Recent evidence suggest emerging role of stem cells in carcinogenesis. This systematic review aimed to synthesizes current knowledge on the role of stem cells in OPMD and MT. Review protocol was developed in accordance with PRISMA 2020 guidelines and registered with PROSPERO. Literature searches identified 4882 records from PubMed, Scopus, Embase, and Web of Science databases; from these, n = 97 primary research studies were selected via two stage screening. Data extraction and narrative synthesis was conducted according to synthesis without meta-analysis (SWiM) guidelines. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal checklists. Studies included in this review were published between 2006-2025, where majority of the research were from India and China. Immunohistochemistry (IHC) was used to identify stem cell biomarkers in tissue samples, most studies demonstrated that higher expression of stem cell markers (CD44, ALDH1, HELLS, TARIF, SOX2, NANOG, and CD147) correlated with severity of epithelial dysplasia. Longitudinal data identified ALDH1 and Bmi-1 as promising prognostic biomarkers linked to MT. Evidence from cell culture and animal model experiments suggested potential therapeutic applications of stem cells and their exosomes in haltering the progression of OPMD. Notably, a clinical trial incorporated stem cell markers as surrogate end points for evaluating treatment options. While findings underscore the prognostic and therapeutic relevance of stem cells in OPMD, lack of prospective designs in biomarker validation and absence of clinical trial evidence on stem cell therapies limit clinical applicability.

Ecotropic viral integration site 1 (EVI1), encoded by the EVI1 gene on chromosome 3q26.2, is a dual-domain zinc finger transcription factor that functions as a potent proto-oncogene in a wide spectrum of hematological malignancies. Under normal physiological conditions, its expression is tightly regulated and restricted primarily to hematopoietic stem cells and specific embryonic tissues. However, aberrant overexpression of EVI1 is a hallmark of aggressive myeloid leukemias, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and the blast crisis of chronic myeloid leukemia (CML). The oncogenic activation of EVI1 occurs through diverse genetic mechanisms, most notably chromosomal rearrangements involving the 3q26 locus, such as inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which juxtapose the EVI1 gene with potent enhancers like that of GATA2. Other mechanisms include the formation of oncogenic fusion genes (e.g., AML1-EVI1, ETV6-EVI1), enhancer hijacking, and retroviral insertional mutagenesis. Once overexpressed, EVI1 drives leukemogenesis through multifaceted molecular actions. It acts as a master transcriptional regulator, profoundly disrupting normal hematopoietic differentiation by repressing key lineage-specific transcription factors like RUNX1 and interfering with cytokine-induced maturation. Concurrently, EVI1 promotes cell survival and proliferation by modulating critical signaling pathways, including the potent inhibition of the tumor-suppressive TGF-β pathway and the activation of the pro-survival PI3K/AKT/mTOR cascade via PTEN suppression. EVI1 also cooperates with a multitude of other oncogenic lesions, such as MLL rearrangements, AML1 mutations, and activated RAS signaling, to accelerate disease progression. Clinically, EVI1 overexpression is one of the most robust independent indicators of poor prognosis, associated with therapy resistance and reduced overall survival. This review provides a detailed discussion of the mechanisms underlying EVI1's activation, its complex molecular functions in hematopoietic transformation, and its profound clinical implications in hematological malignancies.

Retinal ganglion cells (RGCs) play a pivotal part transmitting visual data to the brain. Yet, damaged RGCs are unable to maintain and regrow axons and connectivity, as in the common blinding disease glaucoma. Thus, the idea of rescuing and replacing damaged RGCs holds immense therapeutic potential. In recent years pluripotent stem cells cultured in both 2D and 3D (retinal organoid) environments have generated RGCs from healthy- and patient-derived cells. These models can be used to study normal retinal physiology and compare it to the diseased retina. Although the effects of glaucomatous injuries on RGCs have been well-studied in animal models, much less is known about similar mechanisms in the human retina. Further, using in vitro-derived RGCs as a tool for cell characterization and replacement is still in its infancy. In particular, many distinct RGC subtypes have been described, and it remains unclear how well this diversity is reflected in the various differentiation protocols, or their functional roles in human health and disease. In this review we summarize the currently described subtypes of human RGCs and their markers and discuss recent evidence for subtype-specific vulnerabilities to injury and disease. Finally, we synthesize the limited evidence for subtype differentiation in human stem cell culture approaches. Increased understanding of this human RGC diversity will provide new tools to enrich for selective subtypes and ultimately fill key translational gaps in human glaucoma research.

Peyronie's disease (PD) is an acquired fibrotic condition of the tunica albuginea that is characterized by penile curvature, deformity, pain, and impaired sexual function. PD is prevalent among all ages and is responsible for significant psychological distress. This review summarizes the current knowledge on PD, covering its epidemiology, risk factors, and natural history, along with a comprehensive overview of the medical, intralesional, and surgical options. While the traditional treatments are well-described in previous publications, the focus of the current review is on new biologic and regenerative treatments. Increasing attention to therapies such as platelet-rich plasma and stem cells is representative of the larger trend toward attempts at modifying the underlying fibrotic process, as opposed to merely correcting deformity. By integrating evolving regenerative strategies with proven therapeutic options and prioritizing patient-centered counselling, future PD care may become increasingly individualized, effective, and less invasive.

Organ fibrosis, notably affecting the liver and kidneys, remains a major contributor to global morbidity. This review examines the pathophysiology, molecular mechanisms, and preclinical models used to study hepatic and renal fibrosis. In liver fibrosis, hepatic stellate cell activation, chronic inflammation, and extracellular matrix accumulation are central features, while renal fibrosis involves myofibroblast activation and redox-mediated signaling pathways. The present review highlights both in vitro and in vivo models such as the carbon tetrachloride, bile duct ligation, and dimethylnitrosamine-induced liver fibrosis models, as well as renal fibrosis models like unilateral ureteral obstruction (UUO), subtotal nephrectomy, and adriamycin nephropathy. It also emphasizes advanced experimental platforms including liver slice systems and stem cell transplantation techniques. All these above-mentioned models of hepatic and renal fibrosis involve immune cells directly or indirectly, e.g., cytokines, chemokines, and growth-promoting factors in renal fibrosis UUO model. By integrating molecular insights and experimental techniques, this review provides a comprehensive guide for future therapeutic strategies aimed at mitigating fibrosis in chronic liver and kidney diseases.

The amnion is a transient extra-embryonic tissue whose formation, known as amniogenesis, is vital to amniote embryogenesis. The growing body of knowledge on amniotic lineage emergence and functions has enabled a more comprehensive understanding of the underlying molecular mechanisms and thus may inspire future improvement in stem cell-based amniogenic models. In this Review we first introduce cavitation amniogenesis as a hallmark of human peri-implantation embryogenesis before addressing how cavitation amniogenesis is similar in humans and non-human primates but contrasts with folding amniogenesis in other amniotes such as mice and pigs. We also highlight the ongoing debate of whether primate amniogenesis harbours lineage plasticity for specifying germ cell fate and further discuss the two-wave amniogenesis model and its basis on the pluripotency transition. Finally, we summarize the potential of the recent stem cell-based human embryo models in elucidating amniotic formation and functions.

Ischemic heart disease (IHD) is a leading cause of mortality worldwide, primarily driven by coronary artery stenosis. Current therapies predominantly slow disease progression, with limited capacity to restore functional myocardium. Worsening metabolic disorders significantly drives heart failure. Emerging evidence suggests that stem cell therapy may improve cardiac metabolism. This review examines metabolic dysregulation in IHD and explores how stem cells and extracellular vesicles could modulate these pathways to support tissue repair.

Protein tyrosine phosphatases (PTPs), pivotal regulators of tyrosine phosphorylation dynamics, orchestrate cellular signaling networks to govern fundamental processes such as hematopoietic stem cell (HSC) quiescence, proliferation, and stress responses. Dysregulation of PTPs disrupts tyrosine phosphorylation homeostasis, culminating in HSC dysfunction, malignant transformation and leukemogenesis through aberrant activation of oncogenic pathways. This review summarizes the recent advances in understanding PTP-mediated mechanisms underlying HSC maintenance and leukemogenesis, with a focus on their dual roles as tumor suppressors and context-dependent oncogenic drivers. It could help explore the molecular mechanism of normal hematopoietic homeostasis and provide potential therapeutic targets of the related blood diseases.

A multitude of studies have investigated the identification of unique antigens and genetic traits associated with cardiac stem cells (CSCs) since their discovery. This meta-analysis aims to assess the safety and efficacy of cardiac stem cells (CSCs), elucidate existing knowledge regarding their potential applications, and compare them with other novel therapeutic strategies for cardiac repair, including bone marrow cells (BMCs) and mesenchymal stem cells (MSCs). Researchers conducted a search of important indexing databases, including PubMed, Scopus, Cochrane Central, Web of Science (WOS), CINAHL, and Embase, to identify pertinent papers published from 1980 to January 2025. A total of 74 studies involving 5,420 participants were selected from 459 evaluated for the study. A total of 2,931 participants were allocated to the intervention group, whereas 2,489 were assigned to the placebo or control groups. The research encompassed 49 papers on BMC therapy, 17 on MSC therapy, five on CSC therapy, and three on ADRC therapy. A 0.4% enhancement in left ventricular ejection fraction (LVEF) [95% confidence interval (95% CI): 0.23-0.57; I2: 85%, P < 0.00001] was noted after stem cell therapy and in the stem cell therapy cohort, left ventricular end-systolic volume (LVESV) diminished by -0.33 mL (95% CI: -0.47 to -0.19; I2: 73%, P < 0.00001), whereas left ventricular end-diastolic volume (LVEDV) reduced by -0.18 mL (95% CI: -0.31 to -0.05; I2: 68%, P = 0.006). Furthermore, in this cohort, the six-minute walk test (6MWT) exhibited an increase of 0.2% (95% CI: 0.06-0.34; I2: 0%, P = 0.005), whereas the standardized mean difference of infarct size (IS) demonstrated a reduction of -0.36% (95% CI: -0.60 to -0.12; I2: 68%; P = 0.004). These findings augment the existing evidence and underscore the transformative potential of stem cell therapy in cardiac treatment.

Female breast development occurs at puberty and undergoes many cyclic changes under normal physiological conditions, like pregnancy, lactation and involution. The breast epithelium is surrounded by a heterogenous stroma that encompasses various cell types, including fibroblasts, immune cells, adipocytes, endothelial cells and an extracellular matrix (ECM). The ECM is a complex molecular meshwork composed of a variety of matricellular proteins and ECM remodelling enzymes, including proteases. Dynamic remodelling of the ECM is fundamental to the organisation and function of the mammary gland and is associated with stemness. It is often aberrantly regulated in breast cancer, which still has the highest incidence and mortality rates in women worldwide. Improved models could contribute to a better understanding of cell-matrix interactions, including in the stem cell niche, and ECM remodelling in health and tumorigenesis. This could lay the groundwork for therapeutic strategies that also target the breast cancer ECM for improved precision medicine tools.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets pancreatic beta cells, causing insulin deficiency and hyperglycemia. Unfortunately, till now, no conclusive treatment has been established for the entire treatment of T1DM. Today, Mesenchymal stem cells (MSCs) are widely used in regenerative medicine. MSCs have several advantages, including easy access, strong proliferation ability, differentiation power, minimal risk of tumorigenesis, and low risk of immunogenicity. However, there have been few clinical trials using MSC implants to treat T1DM. In this paper, we look at clinical trials using MSCs to treat T1DM and analyze the benefits and limitations of this approach. To collect crucial data, a comprehensive search was undertaken on articles published between 2015 and 2024. The search involved PubMed, Google Scholar, Embase, CINAHL, PsycInfo, and Cochrane databases. All MeSH words related to mesenchymal stem cells, clinical trials, and type 1 diabetes mellitus were searched. Relevant studies with full access, authored in English from 2015 to 2024, were selected. Ultimately, eleven papers that met the predetermined criteria underwent a comprehensive analysis. This systematic review reveals that MSC treatment is an acceptable treatment option for T1DM, with a positive safety profile observed in the evaluated research. The analyzed findings suggest potential benefits in sustaining beta-cell function and modifying the immunological response, which could lead to a decrease in insulin requirement. However, it remains to be proven as an alternative for insulin administration, and more detailed clinical research is necessary to verify its enduring effectiveness and reliability.

Leukemia is a highly heterogeneous and aggressive hematological malignancy. Current therapeutic approaches (e.g. chemotherapy, radiotherapy, small-molecule targeted therapies, and hematopoietic stem cell transplantation, etc.) are widely limited in clinical practice by systemic drug toxicity, acquired drug resistance, off-target effects, and graft rejection, highlighting the urgent need for safer and more effective innovative treatment strategies.

Once thought to be solely involved in vasculogenesis, tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) has emerged as a crucial marker of progenitor-like cells in the avascular nucleus pulposus (NP), a tissue with notoriously limited regenerative capacity. Recent evidence suggests that TIE2 + NP cells play a pivotal role in disc tissue homeostasis, influencing extracellular matrix maintenance, cellular renewal, and tissue integrity. However, despite the reported regenerative potential of TIE2 + NP cells, their precise function remains enigmatic. This review consolidates in vivo, in vitro, and transcriptomic studies to validate the presence of TIE2 in the NP as a progenitor cell marker. We unravel the complexity of TIE2 + NP cells across species, highlighting key regulatory mechanisms and interspecies variations (including mice, rats, dogs, cows, sheep, pigs, and humans) that may influence their relevance as clinical- and regenerative therapeutic targets. Yet, methodological inconsistencies across studies continue to obscure our understanding of the precise role of TIE2 in NP cell biology. At present, clinical care is limited to managing pain conservatively or resorting to spinal surgery in severe cases. Thus, there exists an urgent need for innovative regenerative strategies to combat disc degeneration and its associated pain and disability. A range of emerging approaches, including biomaterials, gene therapy, and cell-based therapeutics, are under investigation. Within this context, TIE2 + NP cells are of particular interest as potential therapeutic vectors: as for example candidate cells for transplantation, as populations to be stimulated by biologic interventions, or as building blocks in tissue engineering strategies. As progenitor-like cells, they hold the theoretical potential to provide a sustained source of functional NP cells for disc maintenance and repair. By identifying existing knowledge gaps and proposing future research directions, this review aims to clarify their role and accelerate progress toward unlocking their full therapeutic potential.

Ferroptosis is a promising programmed cell death modality for cancer therapy, driven by iron overload and the accumulation of phospholipid peroxides that culminate in lethal membrane damage. Over the past decade, emerging evidence supports the concept that ferroptosis can be harnessed as an effective strategy to suppress tumor growth, particularly in therapy-resistant cancer cells undergoing epithelial-mesenchymal transition and in cancer stem cells. Given that ferroptosis is mechanistically and morphologically different from other known programmed cell death forms, increasing critical findings have shed light on mechanisms by which ferroptosis is regulated, and context-dependent cancer phenotype which is clinical relevant to ferroptosis. In this review, we summarize the basic biology of ferroptosis, including iron regulation and lipid metabolism, as well as key molecular mechanisms such as the system Xc⁻-GSH-GPX4, NADPH-FSP1-CoQ10 and GCH1-BH4 axis in fighting cancer. We also discuss crosstalk between ferroptosis and cuproptosis, disulfidptosis and autophagy, and outline how ferroptosis shapes the tumor immune microenvironment and responses to immunotherapy. More importantly, we highlight the clinical potential of ferroptosis induction via chemotherapy, radiotherapy, immunotherapy and nanomedicine-based delivery strategies, while summarizing common resistance mechanisms and safety considerations. Finally, we outline major challenges and pressing questions for clinical translation, including what are the molecular bases of ferroptosis, how can ferroptosis be leveraged for cancer therapy, how can ferroptosis be integrated with conventional therapies, and how to balance benefits and risks of ferroptosis-based therapy. Collectively, this review connects mechanistic insights with actionable intervention points for developing ferroptosis-based cancer therapies.

Heterogeneity is widely recognised across different cell types. Human oligodendrocyte progenitor cells (hOPCs), essential for myelination, exhibit considerable heterogeneity, which has not been fully characterised. In the current study, by examining the transcriptome of hOPCs at the single-cell level, three distinct subclusters were identified: PRE-OPCs, OPCs, and PRE-OLs. Single-cell RNA-sequencing and RNA-Scope detected high platelet-derived growth factor receptor alpha (PDGFRA) expression. PDGFR-α+ hOPCs exhibited greater myelination, migration, and proliferation capabilities compared to both unsorted hOPCs and PDGFR-α- hOPCs. These enhanced functions may be associated with the activation of the PI3K-AKT-mTOR and TGF-β signalling pathways, which support oligodendrocyte differentiation. hOPCs were induced by hNSCs, their characteristics were identified. RNA-Scope and single-cell RNA Seq sequencing showed PDGFRA were highly expressed at mRNA and protein level. hOPCs were sorted by MACS using PDGFR-α beads. The myelination, migration, and proliferation abilities of PDGFR-α+ hOPCs were higher than that of un-sorting hOPCs and PDGFR-α- hOPCs, possibly being associated with the activation of PI3K-AKT-mTOR and TGF-β signalling pathways, which support oligodendrocyte differentiation (Partly created with Scientific Image and Illustration Software BioRender).

Glutamine synthetase (GS), a key enzyme in nitrogen metabolism, acts as a central node by catalyzing the synthesis of glutamine from glutamate and ammonia, playing a pivotal role in maintaining cellular metabolic homeostasis. Studies have shown that GS is upregulated in various types of tumors, and its expression level is closely associated with tumor initiation, progression, and poor prognosis. This review systematically explores the multifaceted molecular mechanisms through which GS promotes malignant tumor progression. Within the tumor microenvironment, GS enhances the immunosuppressive functions of regulatory T cells (Tregs) and M2-type tumor-associated macrophages (TAMs), thereby inducing immune escape. It also promotes abnormal tumor vasculature by reprogramming metabolism and regulating key cellular behaviors involved in angiogenesis. Furthermore, GS mediates resistance to L-asparaginase and radiotherapy. It also enhances tumor invasion and metastasis via mechanisms including epithelial-mesenchymal transition (EMT). Additionally, this article summarizes potential GS-targeted therapeutic strategies, including small-molecule inhibitors and nano-drug delivery systems, offering theoretical foundations and new directions for reversing tumor drug resistance and developing novel anti-tumor therapies. By comprehensively elucidating the role of GS in multiple malignant processes-including cell proliferation, angiogenesis, invasion and metastasis, immune evasion and therapy resistance-this review aims to provide new insights into precision therapies targeting tumor metabolic reprogramming.

Treatment with umbilical cord blood (UCB) for cerebral palsy (CP) remains promising but experimental and unproven. An updated meta-analysis is needed to assess the efficacy of UCB mononuclear cells (MNCs) in comparison to UCB-derived mesenchymal stromal cells (MSCs) to clarify future directions in the use of UCB to treat CP. An updated systematic review of published controlled clinical trials to November 2024 was conducted and identified ten trials (621 patients; 71% of all patients from 7 trials received UCB-MNCs). Three trials administered UCB-MSCs (30%) and one study compared UCB-MNCs to UCB-MSCs. In one study, MNCs were administered with or without erythropoietin. Eight studies (80%) administered allogeneic cells. Dosage and route of cell administration varied. Clinical outcome reporting was variable, but allowed for meta-analysis of change in GMFM motor scores at 12 months (included 9 groups across 7 studies). Using a random effects model, the standardized mean difference in GMFM scores between baseline and 12 months was higher in the intervention group compared to controls (M= 0.5828, 95% CI=[0.19,0.98], P-value= 0.004). Subgroup analysis using a random-effects model revealed no statistically significant difference in GMFM scores from baseline to 12 months compared to controls in the MNC group (MA = 0.3225, 95% CI = [-0.19, 0.84], P -value= 0.22), whereas in the MSC group, GMFM scores improved more significantly compared to controls (MB = 0.9192, 95% CI = [0.33,1.50], P-value = 0.002). In conclusion, infusion of UCB-MSCs appears promising, with improved GMFM scores at 12 months for patients with cerebral palsy. Larger randomized controlled trials that examine MSCs derived from cord blood and other tissues appears worthwhile. Longer follow-up addressing the breadth of relevant clinical outcomes in CP are needed to confirm potential benefits for patients with CP.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas arising from Schwann cells and characterized by marked cellular and molecular heterogeneity. Although bulk multi-omic studies have provided valuable insights into MPNST biology, recent advances in single-cell profiling have deepened our understanding of the tumor microenvironment and molecular mechanisms underlying malignant transformation. Single cell analyses have revealed distinct Schwann cell-like, malignant neural crest-like, immune, and stromal cellular subpopulations within MPNSTs and their precursor lesions. Comparative profiling of MPNSTs, neurofibromas, and atypical neurofibromatous neoplasms of uncertain biologic potential, suggest that MPNST progression involves Schwann cell dedifferentiation into a more primitive, stem-like state. In this review, we summarize key discoveries from single-cell characterization studies, and discuss how these findings illuminate MPNST tumorigenesis, cellular plasticity, and potential therapeutic vulnerabilities.

Obstructive sleep apnea (OSA) is one of the most common sleep-disordered breathing conditions, characterized by repetitive narrowing or collapse of the pharyngeal airway, associated with chronic intermittent hypoxia (CIH), sleep fragmentation (SF), and sympathetic hyperactivity. Recent epidemiological surveys have shown that OSA may be associated with adverse outcomes, including various diseases and even death. In particular, its association with lung cancer has attracted widespread attention: on the one hand, OSA may promote tumor progression and reduce treatment sensitivity via core mechanisms such as chronic inflammation and oxidative stress; on the other hand, lung cancer itself and its related therapies can conversely exacerbate OSA, forming a complex bidirectional interplay that remains to be fully elucidated. This narrative review systematically searched PubMed and Web of Science databases for literature on OSA and lung cancer published up to September 2025, with a specific focus on mechanistic and clinical observational studies. It aims to clarify the inherent links between the pathophysiological features of OSA and the lung cancer tumor microenvironment (e.g., exosomes, tumor-associated macrophage polarization, and cancer stem cells), further shedding light on the underlying molecular mechanisms, and deepening the understanding of the pathogenic pathways driving OSA-associated lung cancer initiation and progression. Ultimately, this study aims to provide new insights into the clinical management of this comorbid condition and holds significant implications for improving the prognosis of patients with this condition.