The achievements of regenerative medicine are based on methods of controlling stem cell division and differentiation. Electromagnetic fields stimulate cell differentiation by means of affecting calcium channels and cellular signaling. However, only a small part of the mechanisms underlying electromagnetic field effect on cells has been studied. The prospect of their use in tissue engineering as an addition or alternative to biochemical effects becomes clear in the course of numerous experiments. Electromagnetic stimulation enhances the effect of biochemical differentiation inducers and can cause the secretion of exosomes of special properties, which may serve as a therapeutic tool. For example, it has been shown that EMFs at 15 Hz and 2 mT increased the expression of chondrogenic differentiation markers SOX9 and COL2 in human bone-marrow MSCs by up to 3-fold (based on Parate et al.). Optimizing EMF parameters (e.g., 15-50 Hz, 1-2 mT) for specific cells and pathologies remains a key challenge of the studies in the field of tissue engineering. This review describes the electromagnetic field effect on the chondrogenic and osteogenic differentiation of MSCs of various origins, which is important for the musculoskeletal tissue recovery, as well as on inflammatory diseases in model animals.

The Hippo pathway plays a critical role in maintaining tissue homeostasis, regulating organ size, and controlling cellular processes. YAP1/TAZ activation drives oncogenesis, metastasis, and resistance to chemotherapy by promoting key cellular behaviors such as immune evasion and tumor cell survival.

Osteochondral tissue comprises two structurally and functionally distinct regions: An avascular, low-cellularity cartilage layer with poor self-healing capacity, and a vascularized, mineralized subchondral bone. This pronounced heterogeneity complicates the repair of defects that span both regions. Conventional clinical treatments, such as microfracture and autologous chondrocyte implantation, often fail to restore the native biphasic architecture, leading to disorganized fibrocartilage and poor tissue integration. Tissue engineering has emerged as a promising strategy by integrating mesenchymal stem cells (MSCs) with engineered biomaterial scaffolds. However, spatially directing MSCs toward chondrogenic and osteogenic lineages remains challenging. Beyond biochemical cues, biophysical cues play pivotal roles in modulating MSC fate via integrin-mediated mechanotransduction, cytoskeletal remodeling, and mechanosignaling pathways, including TRPV4, Piezo1, and YAP/TAZ. When appropriately encoded within scaffolds, these biophysical cues provide sustained, spatially defined guidance to MSCs. This review summarizes recent advances in scaffold design that leverage mechanobiology to construct biomimetic microenvironments, thereby manipulating lineage-specific MSC differentiation and facilitating layered, stratified osteochondral regeneration.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is pathologically defined by persistent synovitis and systemic inflammation. Currently, the clinical diagnosis and management of RA remain challenging, particularly with respect to early detection, the treatment of refractory cases, and ensuring long-term medication safety. Therefore, it is imperative to deepen our understanding of RA pathogenesis, identify specific biomarkers, and develop innovative therapeutic strategies. This review summarizes the roles and recent advances concerning extracellular vesicles (EVs) in RA progression, diagnosis, and therapeutic development. Research indicates that during RA development, joint-resident cells, immune cells, and relevant body fluids form a complex network in which EV-mediated signaling amplifies inflammatory responses and exacerbates tissue damage. Moreover, studies have shown that EVs isolated from synovial fluid and the circulation of RA patients exhibit significantly altered expression profiles, morphology, or subtype composition. These alterations are closely associated with disease activity, underscoring their potential as diagnostic biomarkers and tools for monitoring disease severity. Regarding therapy, EVs derived from diverse cellular sources have demonstrated promising therapeutic potential in RA. They not only carry bioactive molecules that can modulate RA-associated cells, but also serve as engineered delivery vehicles for targeted therapeutic interventions. In summary, EVs play multifaceted roles in the progression, diagnosis, and treatment of RA. Future research should focus on translating EV-related discoveries into clinical applications, thereby supporting the development of novel strategies for the precise diagnosis and management of RA.

The process of wound healing is intricate and, once disrupted, results in scar formation. Scar formation has negative physiological and psychological impacts on patients in addition to impeding the restoration of skin integrity and function. Increasing evidence indicates that factors such as angiogenesis, ECM deposition, and inflammation are all associated with scar formation. Given their excellent immunomodulatory and regenerative properties, mesenchymal stem cell-derived exosomes (MSCs-Exos) are increasingly favored in inhibiting scar formation during wound healing. This review begins with a summary of the key mechanisms of wound healing and scar formation, followed by the application of MSCs-Exos in attenuating the pathological process of scar formation, as well as its potential mechanisms of action. In addition, the current status and development prospects of engineered exosomes and hydrogel-combined exosomes in scar inhibition are further discussed. Finally, we evaluate the current challenges of using exosomes for scarless wound healing, including manufacturing standardization, dosing, delivery systems, and the lack of large-scale clinical data, which hold the potential to bridge the gap between the laboratory and the clinical.

Chronic kidney disease (CKD) and renal fibrosis remain major global health burdens, with limited options for early diagnosis and effective therapy. Conventional approaches, such as kidney biopsy and imaging, are invasive or insensitive to early-stage changes. Microfluidic technology has emerged as a transformative platform that enables precise modeling of renal microenvironments, sensitive biomarker detection, and physiologically relevant drug testing. This review evaluates recent advances in microfluidics for CKD and fibrosis, with emphasis on mechanistic insights, diagnostic innovations, and therapeutic strategies.

Cell-based therapy is a promising approach for ischemic stroke treatment. This systematic review and meta-analysis aimed to consolidate clinical evidence on the use of neuroimaging to evaluate stem cell therapy across all stages of stroke recovery.

The development of techniques to culture and differentiate adult and pluripotent stem cells into diverse cell types over the past decades has sparked an increasing interest in the use of cells for organ regeneration. Such therapies aim to replace lost or damaged cells with functional ones. This can be achieved either through tissue engraftment of therapeutic cells or via their paracrine effects on resident cells, thereby offering a potential cure for debilitating degenerative diseases. The development of regenerative cell therapies, however, is ultimately complex. Effective cell therapy requires the delivery and successful engraftment of therapeutic cells to the correct location or sufficient paracrine activity, while ensuring safety is key to gaining support from funders, caregivers, and patients. A wide variety of cell sources has been used for the development of regenerative cell therapies, ranging from mesenchymal stromal cells (MSC) that act to stimulate local progenitor cells through their secretome to tissue-specific cell types differentiated from adult or pluripotent stem cells and organoids that engraft in tissues. While cell administration to patients is challenging based on both practical and ethical perspectives, the development of techniques to preserve transplant organs ex situ on machine perfusion devices offers a unique opportunity for studying regenerative cell therapy for organ repair in a safe and controllable environment. The present review addresses the current progress of cell therapy for organ regeneration of the intestine, kidney, liver, lung, and heart and discusses the challenges and opportunities of this potentially curing therapeutic approach.

Hematopoietic stem cells (HSCs) are the lifelong source of hematopoietic cells, maintained within the specialized microenvironment of the bone marrow. A central question remains regarding the mechanisms that regulate HSC maintenance. Functional studies have advanced our knowledge of the HSC niche, which consists of perivascular stromal, skeletal, and endothelial cells. Understanding the HSC niche is particularly important in the context of myeloablation which disrupts both the hematopoietic cells and their supporting microenvironment. As a clinical intervention, myeloablation followed by HSC transplantation is a well-established treatment option that has been shown to improve prognosis and increase survival in patients. These positive outcomes result from the reconstitution of the hematopoietic system by transplanted HSCs with the support of the regenerated microenvironment.

Gene-modified hematopoietic stem cell transplant (GM-HSCT) is an innovative curative therapy for transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD), which has demonstrated excellent efficacy in clinical trials. Two commercial products are currently available, with several additional products in clinical trials. GM-HSCT requires the mobilization and subsequent collection of hematopoietic stem and progenitor cells (HSPCs) by apheresis. Current protocols consistently demonstrate effectiveness in collecting HSPCs in patients with TDT. However, disease-specific characteristics of SCD create challenges in collecting HSPCs. Further research remains in optimizing collection procedures in this population.

Apheresis is an essential modality for collecting blood and blood components from blood donors, as well as for providing therapeutic relief to patients. In both cases, apheresis is generally very well tolerated and is widely viewed as a safe procedure. In this review, we describe the most common apheresis procedures, indications for therapeutic apheresis, and the role that apheresis collections play in cellular therapies.

Colon cancer (CC) constitutes a significant global health challenge, characterized by increasing incidence and mortality rates that underscore the necessity for continued investigative efforts. Inflammation-driven cellular and molecular processes are fundamentally implicated in the CC development, progression and pathogenesis. Among these immune effectors, T helper 17 (Th17) cells, a distinct subset of CD4+ T lymphocytes, are integral to inflammatory and autoimmune responses and modulate antitumor immunity. In CC, Th17 cells exhibit a dualistic function; they may promote tumorigenesis by sustaining chronic inflammation or exert antitumor effects by enhancing cytotoxic immune response. Notably, critical gaps persist in understanding how Th17 plasticity dynamically governs the balance between immune surveillance and tumor immune evasion, representing a central unresolved controversy in CC progression. Furthermore, while extensive research has shown that Th17 cells interact with the tumor microenvironment (TME) and cancer stem cells (CSCs), the specific mechanisms behind these interactions that facilitate metastasis, invasion, and cellular proliferation are still not fully understood. Several studies have documented an increased proportion of Th17 cells in the peripheral circulation of CC patients. However, conflicting clinical evidence regarding their prognostic significance highlights a major translational challenge for patient stratification and targeted intervention. This review consolidates novel perspectives on the multifaceted contributions of Th17 to CC initiation, progression, and therapy, emphasizing targeted interventions to disrupt inflammatory axes and improve outcomes.

Articular cartilage regeneration remains a formidable challenge due to the tissue's limited intrinsic healing capacity. This review synthesizes current knowledge in cartilage tissue engineering (CTE) through the pivotal lens of the cartilage niche-the dynamic, multicellular microenvironment essential for development, homeostasis, and repair. We first deconstruct this niche into its core components: the cellular consortium of chondrocytes, progenitors, and supportive cells; the extracellular matrix (ECM) as a bioactive, mechanosensitive scaffold; the intricate biochemical signaling network governing anabolic-catabolic balance; and the critical biophysical and mechanical cues that direct chondrocyte fate. The review then analyzes advanced strategies to engineer this niche, encompassing scaffold-based approaches using smart biomaterials and 3D bioprinting, cell-based strategies involving chondrocytes, Mesenchymal Stem Cells (MSCs), and induced pluripotent stem cell (iPSCs) with preconditioning protocols, and the application of physiologically relevant biophysical stimuli via bioreactors. This review distinguishes itself by explicitly focusing on cartilage-specific niche biology, integrating host-environment interactions, and critically evaluating translational gaps. Despite significant progress, the field confronts persistent challenges, including the gap between engineered constructs and native tissue complexity, difficulties in achieving scalable manufacturing and robust host integration, and the hurdle of creating vascularized osteochondral units. We conclude that the future of CTE lies in a convergent, holistic approach that moves beyond mimicking individual components to designing integrated, biomimetic systems. Leveraging innovations in 4D bioprinting, intelligent materials, and personalized medicine will be crucial to engineer functional cartilage that achieves lasting clinical integration and restores joint function.

Organoid technology has rapidly evolved as a transformative tool for modeling human physiology and disease. Organoids are three-dimensional, stem cell-derived constructs that self-organize to recapitulate key structural and functional features of native organs. Among known organoids, brain organoids have provided unprecedented insights into human neurodevelopment and pathophysiology, overcoming the limitations of traditional two-dimensional cultures and animal models. These models closely mimic the architecture, cellular diversity, and regional specification of the human brain, offering a physiologically relevant platform for mechanistic studies. Therefore, brain organoids have become indispensable for investigating complex neurological disorders, such as Alzheimer's disease, Parkinson's disease, and schizophrenia.

Klotho is an anti-aging protein with multiple functions in maintaining homeostasis within the central nervous system (CNS). Klotho-induced neurogenesis and oligodendrogenesis play a critical role in myelination, neuroplasticity, and hippocampus-dependent cognition. In this context, the objective of this review is to synthesize well-established information about the mechanisms through which Klotho influences neurogenesis and oligodendrogenesis. Previous studies have demonstrated that Klotho regulates adult neurogenesis, stimulates the proliferation of neural progenitor cells (NPCs), promotes the differentiation of NPCs into neurons, and facilitates neuronal maturation and dendritic arborization. Additionally, Klotho stimulates oligodendrocyte differentiation and maturation, as well as myelination throughout life. The reviewed evidence suggests that Klotho influences cell fate decisions during both development and adulthood and has a modulatory role in neuronal fate determination from embryonic stem cells in neurogenesis and oligodendrogenesis. Therefore, Klotho may represent a promising therapeutic target for neuroprotection, including the prevention of neurodevelopmental and neurodegenerative diseases.

Exosomes derived from dental stem cells (DSC-Exos) are nanovesicles (~ 30–150 nm) that mediate angiogenesis, odontoblastic differentiation, and immune regulation, positioning them as promising cell-free candidates for pulp–dentin regeneration. This PROSPERO-registered systematic review evaluated the regenerative potential of DSC-Exos and the methodological factors influencing outcomes. A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted through July 2025; risk of bias was assessed using RoB 2.0, SYRCLE, and QUIN tools. Thirteen studies fulfilled the inclusion criteria, most of which employed exosomes derived from human dental pulp stem cells, stem cells from human exfoliated deciduous teeth and stem cells from the apical papilla. DSC-Exos consistently promoted cell proliferation and migration while upregulating odontogenic (DSPP, DMP1) and angiogenic (VEGF, CD31) markers. Animal models demonstrated vascularized pulp-like tissue and organized tubular dentin formation, significantly enhanced by donor-cell preconditioning and biodegradable carriers. Mechanistic investigations linked these outcomes to noncoding RNAs and signaling axes like miR-26a/TGF-β and circ_0003057/EIF4A3/ANKH. A 24-month clinical pilot confirmed restored pulp sensitivity without safety concerns. Nevertheless, the overall certainty of evidence remains moderate to low, mainly due to substantial methodological heterogeneity, limited sample sizes and insufficient reporting of critical parameters such as exosome characterization, dosing strategies and operator calibration. Collectively, the findings indicate that DSC-Exos represent a high-potential biomimetic strategy for pulp–dentin regeneration; however, standardized characterization protocols in line with MISEV guidelines, dose harmonization and well-designed long-term controlled clinical trials are essential before cell-free endodontic therapies can be reliably incorporated into clinical practice.

The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes. Wiskott-Aldrich syndrome usually presents in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; recurrent bacterial, viral, fungal, and/or opportunistic infections; and eczema. Approximately 25%-40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, vasculitis, rheumatoid arthritis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have small platelet volume and thrombocytopenia. Severe disease-related events include severe bleeding episodes (14%), autoimmunity (12%), life-threatening infections (7%), and malignancy (5%). Males with XLN typically have congenital neutropenia associated with myelodysplasia, hyperactive neutrophils, increased myeloid cell apoptosis, and lymphoid cell abnormalities.The diagnosis of a WAS-related disorder is established in a male proband with both congenital thrombocytopenia (<70,000 platelets/mm3) and small platelet size; at least one of the following features: eczema, recurrent bacterial, viral, and fungal infections, autoimmune disease(s), malignancy, reduced WASP expression in a fresh blood sample, abnormal antibody response to polysaccharide antigens and/or low isohemagglutinins, or positive maternal family history of a WAS-related disorder; and a hemizygous WAS pathogenic variant identified by molecular genetic testing (necessary to confirm the diagnosis). The diagnosis of a WAS-related disorder in a female is uncommon. It is usually established by identification of a heterozygous pathogenic variant in WAS by molecular genetic testing in a female with severe skewed X-chromosome inactivation and increased expression of the mutated WAS allele.Targeted therapies: Curative targeted therapies clinically available for Wiskott-Aldrich syndrome include allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy. Treatment of manifestations: In those with Wiskott-Aldrich syndrome and XLT, treatment is individualized based on disease manifestations and includes management of thrombocytopenia; prevention of infection with immunoglobulin replacement; topical steroids for eczema; antibiotics as needed for chronic skin infections; prophylactic antibiotics for Pneumocystis jirovecii in infants with Wiskott-Aldrich syndrome; intravenous immunoglobulin G; routine non-live immunizations; prompt evaluation and treatment for infection including empiric parenteral antibiotics and exhaustive search for source of infection; and judicious use of immunosuppressants for autoimmune disease prior to definitive treatment. In those with XLN, treatment includes granulocyte colony-stimulating factor therapy; routine non-live immunizations; prompt evaluation and treatment for infection including empiric parenteral antibiotics and exhaustive search for source of infection; and treatment of myelodysplastic syndrome and acute myelogenous leukemia per hematologist/oncologist. Surveillance: Complete blood count including platelet count and size and assessment for complications associated with increased bleeding as recommended by hematologist; annual skin examination; assessment by immunologist including for recurrent infections with frequency as recommended by immunologist; annual clinical assessment for autoimmune dysfunction and for manifestations of lymphoma. Agents/circumstances to avoid: Circumcision of at-risk newborn males who have thrombocytopenia; use of medications that interfere with platelet function. Defer elective procedures until after HSCT. Evaluation of relatives at risk: Evaluation of at-risk newborn males so that morbidity and mortality can be reduced by early diagnosis and treatment. Evaluation of relatives considering stem cell donation to inform transplant donor decision making.WAS-related disorders are inherited in an X-linked manner. If the mother of the proband is a carrier of the WAS pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be symptomatic. Females who inherit the pathogenic variant will be carriers and are typically asymptomatic. Males with a WAS-related disorder transmit the pathogenic variant to all of their daughters and none of their sons. Once the WAS pathogenic variant has been identified in a family member, molecular genetic testing to identify female heterozygotes and prenatal and preimplantation genetic testing are possible.Copyright © 1993-2026, University of Washington, Seattle. 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To update the ASCO guideline on use of hematopoietic colony-stimulating factors (CSFs) in patients with cancer.

Glioblastoma is a highly aggressive primary brain tumour marked by extensive genomic and epigenomic alterations, cellular heterogeneity, and therapeutic resistance. Despite maximal surgical resection followed by chemoradiotherapy, median survival remains approximately 15 months, reflecting the tumour's invasive behaviour and adaptability. Advances in molecular oncology have revealed two promising therapeutic directions: epigenetic reprogramming and neurogenetic modulation. Glioblastoma exhibits widespread epigenetic dysregulation that disrupts transcriptional control, enhances cellular plasticity, and drives tumour progression. Concurrently, glioma cells aberrantly reactivate developmental programmes, acquiring neural stem cell-like states governed by transcription factors and signalling networks such as SOX2, OLIG2, Notch, and Wnt. These pathways collectively sustain stemness, lineage mimicry, and therapy resistance. This review proposes a focused conceptual framework centred on epigenetic and neurogenetic modulation as two core regulatory layers shaping glioblastoma plasticity and adaptive resistance. We highlight how DNA methylation, histone modifications, and chromatin remodelling contribute to transcriptional dysregulation, and how neurodevelopmental signalling reinforces malignant plasticity. Emerging preclinical and clinical studies combining epigenetic inhibitors with differentiation- or reprogramming-based therapies are discussed. By uniting mechanistic insights from chromatin biology, neurodevelopment, and cancer therapeutics, this integrative conceptual framework offers a structured lens for targeting key vulnerabilities underlying glioblastoma plasticity. The integration of these complementary strategies offers potential to enhance therapeutic responsiveness and improve disease management in this devastating malignancy.