Acute myeloid leukemia (AML) is caused by uncontrolled proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Historically, research has emphasized the role of protein-coding genes in the development of AML. However, with the human genome project revealing that 98% of the transcriptome consists of non-protein-coding RNAs, recent studies have explored how the large classes of noncoding RNAs (ncRNAs) contribute to AML. Although there are many types of ncRNAs, much attention has been placed on understanding the function of long ncRNAs (lncRNAs) and small ncRNAs known as microRNAs (miRNAs). lncRNAs are >200 nucleotides, whereas mature miRNAs are typically 18 to 25 nucleotides. lncRNAs are involved in miRNA and protein sequestration and act as transcriptional and translational regulators, whereas miRNAs facilitate mRNA degradation and translational inhibition. In addition to lncRNAs and miRNAs, two additional types of ncRNAs, namely small nucleolar RNAs (snoRNAs) and circular RNAs (circRNAs), have recently garnered attention for their roles in AML. Here, we discuss how these four distinct classes of ncRNAs may aid in disease diagnosis and prognosis as well as the mechanisms by which their dysregulation contributes to AML.

Osteoarthritis (OA) is a highly prevalent degenerative joint disease whose complex pathological microenvironment and limited cartilage self-repair capacity have resulted in the absence of therapeutic approaches capable of simultaneously achieving structural reconstruction and functional recovery. Current clinical strategies face significant limitations, as conventional pharmacological treatments can only alleviate symptoms with accompanying systemic side effects, while surgical interventions often encounter challenges such as inadequate mechanical properties of repaired tissues and long-term degeneration. The precise functionalization of injectable hydrogels represents a key strategy for cartilage regeneration and the core challenge lies in integrating multiple material properties to design on-demand delivery platforms that can dynamically respond to complex pathological microenvironments in vivo. This review systematically elaborates on precision customization strategies for injectable hydrogels based on OA pathological mechanisms, focusing on how hydrogel design responds to pathological signals in the joint microenvironment to achieve on-demand and precise regulation of therapeutic agents including drugs, cells and genes. Beginning with cartilage structure and injury mechanisms, this article analyzes the limitations of existing pharmacological and surgical repair methods, then, elaborate on the multifunctional platform role of hydrogels in cartilage tissue engineering, including recent advances in mechanical design, drug loading/release behavior, inflammation regulation, stem cell delivery and gene-activated repair. Finally, it outlines challenges and future directions for smart hydrogels in cartilage regenerative medicine, aiming to provide a theoretical framework and technical pathway for integrating materials science with clinical medicine.

Radial glia are a specialized population of neural progenitor cells that persist throughout embryogenesis and into adulthood. Throughout this period, radial glia reside in a highly dynamic microenvironment that influences various biological decisions that govern typical cortical development. Subsequently, radial glia must fine-tune their responses to numerous environmental cues throughout development. The establishment of the cortical vasculature coincides with neurogenesis and dramatically alters the radial glia microenvironment by increasing oxygen and metabolite delivery. In addition, a synergistic spatial relationship between radial glia and endothelial cells regulates multiple aspects of radial glial biology. Here, we discuss crosstalk between radial glia and the cortical vasculature/endothelial cells throughout development, including the influence of extrinsic angiogenic processes and our growing understanding of the intricate spatial relationships between radial glia and endothelial cells.

This article offers an in-depth review of the design and modeling of 3D-printed hip prostheses, emphasizing the integration of regenerative medicine, especially in the context of custom Rapidly Destructive Osteoarthritis implants. It traces the history of Total hip arthroplasty and current implant materials, along with recent advances in tissue engineering strategies and biofunctionalization methods to enhance biological integration. Computational processes are examined, including segmentation, image processing, computer-aided design, finite element analysis, and CAE simulations. It also discusses techniques in additive manufacturing that control porosity and stiffness, as well as strategies for recruiting host stem cells. The overall performance of existing THA approaches, combined with reliance on outdated surgical workflows and the complexity of clinical standards, creates challenges for the adoption of innovative implant research and limits broader application. International standards (ISO/ASTM), regional regulations (MDR, FDA), ethical considerations, and professional design guidelines are crucial components of this review, guiding safety, reproducibility, and the clinical impact of next-generation THA solutions. Finally, this review proposes a novel 'regenerative design' paradigm. Distinct from traditional biointegration methods, this framework integrates patient-specific imaging, mechanobiology-based architecture optimization, and biologically calibrated simulation to direct endogenous cell recruitment and vascularized healing explicitly.

The 38 currently registered clinical trials with the keyword "adult neurogenesis" indicate growing interest in new neurons as a target for intervention. Today, we have strong evidence that adult neurogenesis is involved in hippocampal function and can contribute to brain functions in health and disease. Neurogenesis research can now ask new questions, such as (1) the identity of stem cells and their input integration for initiating neurogenesis, (2) the nature of the neurogenic niche and neurogenesis without stem cell activity, (3) the complex functionality beyond the hippocampus, and (4) evolutionary and computational theory, including neurogenic neural networks for artificial intelligence.

Twenty years have passed since the first demonstration of mouse induced pluripotent stem cells (iPSCs). What began as an unexpected observation in Kyoto quickly transformed stem cell biology and regenerative medicine worldwide. Over the past two decades, we have gained profound insights into the molecular mechanisms underlying cellular reprogramming and pluripotency. The technology has continued to evolve-becoming safer, more efficient, and more versatile. Today, iPSCs serve as a foundation for wide-ranging applications, from disease modeling and drug discovery to regenerative therapies and rejuvenation research. In this review, I reflect on the scientific journey of iPSCs, highlight key milestones in our understanding of reprogramming, and discuss the expanding clinical and societal impact of iPSCs.

Ischemic heart disease, which leads to the loss of functional myocardium, remains the leading cause of death in late adulthood. Epicardial patches have emerged as a promising adjunctive strategy for myocardial repair. However, owing to the thick epicardial barrier (epicardial adipose tissue), only a select few approaches have demonstrated reduced scarring and improved heart function in large animal models and early-stage human trials. In this opinion article, we examine the different mechanisms and approaches to overcome the epicardial barrier. We further discuss key design and material considerations to improve safety and efficacy in clinical applications. Finally, we provide a summary of current regulatory and clinical challenges, together with proposed future research directions and foci in the translation of epicardial patches.

Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem and progenitor cells carrying somatic mutations and is increasingly identified in oncology through cell-free DNA testing. Once regarded mostly as a precursor to myeloid neoplasms and a contributor to cardiovascular disease, CH is now recognized as a major determinant of clinical outcomes in patients with cancer. Specific anticancer agents selectively promote the expansion of clones with DNA damage response gene mutations, particularly those with TP53 or PPM1D mutations, which are strongly associated with myeloid neoplasms post cytotoxic therapy (MN-pCT). The extent of clonal growth varies with treatment and, in some cases, may regress once therapy is withdrawn. In addition to therapy-driven clonal selection, inflammatory stress accelerates clonal expansion, creating a self-reinforcing cycle that contributes to atherosclerosis and other inflammation-associated complications. In oncology, CH-derived immune cells can infiltrate the tumor microenvironment and remodel local immunity, influencing tumor growth and treatment response. This tissue-infiltrating form of CH, termed tumor-infiltrating CH, has been associated with inferior survival in some cancer cohorts. Together, these findings establish CH as both a clinical challenge and an opportunity in modern oncology. Dedicated CH clinics and molecular tumor boards are emerging to address its implications for risk stratification, treatment selection, and survivorship care. This review examines the biology and clinical impact of CH in oncology, including its mutational spectrum, clonal evolution, role in MN-pCT, effects on inflammation and the tumor microenvironment, and emerging strategies for risk assessment and patient management.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a dismal 5‑year survival rate of ~9%, primarily due to late diagnosis, aggressive metastasis and profound resistance to conventional therapies. Epithelial‑mesenchymal transition (EMT) has been identified as a pivotal driver of these malignant phenotypes, facilitating early invasion, dissemination and treatment failure. The present review systematically elaborated on the multidimensional mechanisms underlying EMT in PDAC, emphasizing its operation as a spectrum of hybrid epithelial/mesenchymal states rather than a binary switch. Key molecular mechanisms include the activation of core transcription factors (such as Snail, ZEB, Twist), intricate crosstalk within the tumor microenvironment (such as transforming growth factor-β and hepatocyte growth factor signaling from stromal cells) and dynamic epigenetic reprogramming. Furthermore, EMT critically contributes to the acquisition of cancer stem cell properties and enhances the survival and colonization of circulating tumor cells. The present review also outlined emerging translational strategies targeting EMT‑related pathways, highlighting agents such as STNM01 that have entered early-phase clinical trials. By synthesizing unprecedented insights into EMT's plastic spectrum states and subtype‑specific regulatory networks, this work establishes a paradigm‑shifting framework for advancing EMT‑targeted therapies; offering transformative potential to overcome PDAC's historical therapeutic barriers and substantially improve patient survival outcomes. By synthesizing current insights from molecular pathways to therapeutic applications, the present review confirmed EMT as a promising therapeutic target and provides a strategic framework for advancing PDAC treatment, with the ultimate goal of improving clinical outcomes.

Growing evidence has supported the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot and lower extremity peripheral artery disease (PAD), but their results are not consistent. Thus, the authors conducted the first meta-analysis concerning the safety and efficacy of UCMSC treatment in diabetic foot patients. 8 English and Chinese databases were searched to identify randomized controlled trials regarding UCMSC therapy in diabetic foot patients. Two independent investigators carried out literature inclusion, data extraction, and quality assessment. Meta-analysis was performed using ReviewManager 5.4.1., 6 RCT studies involving 380 patients were included. Primary endpoints included ulcer healing, transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), and intermittent claudication. Compared with conventional treatment, patients who accepted UCMSC therapy had a better ulcer healing rate (Odds Ratio (OR) = 2.88 [1.20-6.91]), TcPO2 (standardized mean difference (SMD) = 1.39, [0.01-2.77]), and ABI improvement (SMD=1.22 [0.30-2.13]). Moreover, they also experienced significantly better improvements in pain amelioration, skin temperature, and ulcer area reduction. Whereas, intermittent claudication cannot be ameliorated by UCMSC therapy (SMD=0.83 [-0.45-2.10]). Additionally, neovascularization, examined by angiography, was significantly promoted after UCMSC administration. Moreover, two studies recorded adverse events during follow-up, which were considered to be transient, minor, and regional. The present meta-analysis validated that UCMSC treatment enhances diabetic foot ulcer healing and circulation recovery, and has a promising safety profile, though limited by incomplete reporting. Larger-sample multicenter randomized controlled trials and longer-term follow-up are urgently needed to further explore the safety and efficacy of UCMSC treatment in diabetic foot patients. The meta-analysis was prospectively registered on PROSPERO.

Lentiviral vectors (LVs) have revolutionized gene therapy by enabling stable gene integration into dividing and non-dividing cells, addressing critical challenges in treating genetic disorders. The transition from second to third-generation LVs has increased biosafety by minimizing the risk of replication-competent lentiviruses and expanded their clinical applicability. Despite significant advancements, producing high-titer functional LVs, particularly at an industrial scale, remains a considerable challenge due to the need for enhanced scalability, cost-efficiency, and effectiveness. This Review delves into cutting-edge innovations in LV production, from optimized transient transfection in various cell lines to the development of stable producer cell lines. Stable producer cell lines offer unparalleled scalability but face challenges related to viral protein cytotoxicity. Inducible systems have emerged as pivotal tools for addressing these problems, allowing for precise gene expression and controlled production. Additionally, advancements in bioprocess engineering, ranging from optimized culture conditions, including pH and media composition, to novel bioreactor technologies like structured fixed-bed systems, continue to redefine industrial-scale LV production. These breakthroughs, coupled with the analysis of costs and efficiencies of various methodologies, can further illustrate the potential for large-scale LV production and facilitate widespread therapeutic applications.

Introduction: Spinal cord injury (SCI) is among the most severe medical conditions, with profound impacts on global healthcare systems. SCI results in temporary or permanent loss of spinal cord function and is associated with high incidence rates, substantial economic burden, significant disability, and a low average age of onset. Astrogliosis and neuroinflammation play central roles in secondary injury and limit functional recovery. This systematic review examines pathophysiology, mechanisms of recovery, and emerging clinical treatment strategies for SCI. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies on SCI classification, pathophysiology, and treatment approaches, with a particular focus on Exosome and low level Laser therapy. The search included articles published up to September 2024, and key data were extracted for analysis. Results: A total of 141 studies met the inclusion criteria. The pathogenesis of SCI involves an initial mechanical injury followed by a secondary cascade of molecular and cellular events that exacerbate tissue damage. Current treatment options primarily provide supportive care for patients with lifelong disabilities. Pharmacological interventions focus on neuroprotection, employing medications and therapeutic agents tailored to modulate degenerative processes. Non-pharmacological approaches, including growth factors, Low level laser therapy, cultured cells, and vitamins, offer additional therapeutic benefits. Laser therapy integration into SCI treatment is increasingly studied due to its anti‑inflammatory, neuroprotective, and analgesic effects. Exosome therapies have shown significant neuroprotective and neuroregenerative potential by addressing multiple pathological mechanisms in SCI. Conclusion: A promising future direction lies in combining conventional pharmacological and surgical strategies with emerging therapies, particularly exosome therapy and LLLT, offers a promising approach to mitigate secondary injury, modulate astrogliosis, and enhance recovery in SCI patients. Comprehensive therapeutic strategies integrating pharmacological and non-pharmacological approaches with cutting-edge cell therapies hold significant promise for improving outcomes in SCI treatment.

T cell fitness has emerged as a critical determinant of the efficacy and persistence of Chimeric Antigen Receptor (CAR)-T cell therapy. Defined by the capacity of T cells to proliferate, resist exhaustion, persist in vivo, and exert sustained effector functions, T cell fitness reflects the integration of a dynamic network of intrinsic and extrinsic regulatory mechanisms. In this review, we present a comprehensive synthesis of the molecular and cellular foundations underlying T cell fitness, emphasizing the influence of differentiation trajectories, signaling pathways, metabolic reprogramming, and epigenetic modifications. We further discuss the impact of patient-specific conditions such as age as well as disease biology, prior therapeutic exposures, and timing and quality of T cell collection, on the phenotypic and functional efficacy of CAR-T cell products. Beyond delineating these determinants, we highlight emerging strategies aimed at enhancing T cell fitness. Importantly, we propose T cell fitness as an integrated, multi-layered systems property emerging from the interaction between differentiation state, signaling architecture, metabolic-mitochondrial competence, epigenetic stability, and host-specific inflammatory and treatment-related pressures. We introduce a mechanistic framework that links these layers across the CAR-T therapeutic timeline from leukapheresis to post-infusion tumor engagement and outline how this framework can be operationalized into measurable parameters to guide patient stratification, manufacturing decisions, and rational therapeutic interventions.

Silicosis is an irreversible fibrotic interstitial lung disease triggered by chronic exposure to respirable crystalline silica (RCS). Currently, effective therapeutic interventions for this disease remain lacking, as existing clinical approaches are limited to mitigating disease progression rather than reversing or halting pathological changes. Stem cell-based therapies have emerged as a promising therapeutic modality for silicosis, leveraging their inherent biological properties to target key pathogenic cascades, such as NLRP3 inflammasome activation, TGF-β1/Smad-mediated fibrotic progression, and Th1/Th2 immune homeostasis imbalance. Notably, mesenchymal stem cells (MSCs) have advanced to early-phase (I/II) clinical trials for related pulmonary fibrotic diseases, demonstrating preliminary safety and potential for stabilizing lung function. This review synthesizes the latest advancements in stem cell-based therapeutic strategies for silicosis, with a systematic comparison of three key cell sources. The discussion encompasses adult stem cells, such as the readily accessible and immunomodulatory mesenchymal stem cells (MSCs) and the epithelium-regenerative airway basal stem cells (ABSCs), as well as the pluripotent but ethically debated induced pluripotent stem cells (iPSCs). Additionally, this review discusses critical challenges impeding the clinical translation of these therapies, including the standardization of GMP-compliant production processes, suboptimal homing efficiency of transplanted stem cells within the fibrotic pulmonary microenvironment, and inherent safety risks. Finally, this review highlights innovative translational strategies-such as CRISPR-engineered stem cells, stem cell-driven nano-delivery systems, and alveolar organoid models-and underscores the future potential of combination therapies and targeted approaches for silicosis-associated comorbidities. By integrating current knowledge, analyzing translational barriers, and exploring these forward-looking directions, this review aims to provide both theoretical insights and practical guidance for advancing the development and clinical application of stem cell-based therapies for silicosis.

Autoimmune thyroiditis (AIT), typified by Hashimoto's thyroiditis, represents a prototypical organ-specific autoimmune disorder marked by lymphocytic infiltration, autoantibody production, and progressive thyroid dysfunction. Conventional hormone replacement alleviates hypothyroidism but fails to correct the underlying immune dysregulation. Preclinical models of experimental autoimmune thyroiditis (EAT) consistently demonstrate that these cell-based approaches mitigate inflammatory responses, correct Th17/Treg imbalance, and prevent follicular destruction. Moreover, emerging data on extracellular vesicle-mediated mechanisms and antigen-specific dendritic targeting further underscore the potential for durable immunological reprogramming. This review summarizes recent advances in tolerogenic cellular therapies aimed at restoring immune homeostasis in AIT. Mesenchymal stem cells (MSCs), regulatory T cells (Tregs), and tolerogenic dendritic cells (tolDCs) exert multifaceted immunomodulatory effects via cytokine secretion, metabolic reprogramming, and induction of antigen-specific tolerance, offering a promising immunotherapeutic strategy to modify AIT progression, moving beyond symptomatic relief toward long-term immune tolerance.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR-Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges-including insufficient maturation, lack of vascularization and immune components, and batch variability-the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)-driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.

As global societies age, the prevalence of neurodegenerative disorders, such as Alzheimer's disease, is rapidly increasing, intensifying the need to understand the mechanisms of aging and their contribution to these conditions. Consequently, the focus of aging research has shifted from the traditional concept of chronological age to a more nuanced understanding of biological age. This has spurred active investigation into robust biomarkers, including cellular senescence. However, the application of classical senescence markers to the brain presents a substantial challenge, as their validity in post-mitotic cells, such as neurons, remains unclear. In this review, we highlight the limitations of the current metrics for cellular senescence as indicators of biological aging, and propose a path forward focused on identifying and modeling cell-type-specific aging markers within the brain.

Hematopoietic stem cell transplantation (HSCT) is a cornerstone in the treatment of hematological disorders. However, its application is frequently complicated by acute and chronic graft-versus-host disease (aGVHD/cGVHD), pathological conditions in which donor-derived immune cells attack host tissues. With suboptimal survival rates and limited therapeutic options, GVHD remains a major clinical challenge. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality due to their immunomodulatory capabilities, yet standardized protocols for their use in preventing or treating GVHD have not been established.