Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) , and achieving complete remission (CR) is a critical step before allo-HSCT. Recent studies have shown that immunotherapy with the bispecific T-cell engager (BiTE) blinatumomab can eliminate residual chemotherapy-resistant B-ALL cells, significantly improve remission rates in patients with relapsed/refractory B-ALL and those with positive minimal residual disease (MRD) , successfully bridge patients to allo-HSCT, and provide additional options for post-transplant relapse management and maintenance therapy. This article reviews the application strategies of blinatumomab in adult B-ALL.

This study aimed to explore the application of CAR-T cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with diffuse large B-cell Richter syndrome, and to review recent advances in the diagnosis, pathogenesis, and treatment of this disease. We retrospectively analyzed the diagnosis and treatment course of one patient diagnosed with Richter syndrome at Binzhou Medical University Hospital and reviewed relevant literature. The patient was a 49-year-old female with a history of chronic lymphocytic leukemia (CLL) for over two years, who presented with a progressively enlarging right neck mass, and was ultimately diagnosed with transformation of CLL into diffuse large B-cell lymphoma (DLBCL) , i.e., Richter syndrome. The patient initially achieved a partial response after three cycles of R-DA-EPOCH combined with zanubrutinib therapy. Following disease progression, the treatment regimen was adjusted to a combination of PD-1 monoclonal antibody, CD20 monoclonal antibody, XPO1 inhibitor, and zanubrutinib for one cycle. This was followed by infusion of autologous anti-CD19 CAR-T cells and subsequent bridging to allo-HSCT. Assessments at 3 and 8 months post-transplantation both demonstrated disease complete remission.

Chronic myelomonocytic leukemia (CMML) is one of myeloid neoplasms originating from hematopoietic stem/progenitor cells, featuring both myelodysplastic and myeloproliferative characteristics. Significant revisions have been made to the diagnostic and classification criteria for CMML in the 5th edition WHO classification (WHO 2022) and the International Consensus Classification (ICC) . Furthermore, besides the previously proposed CMML-specific prognostic scoring system (CPSS) , newer prognostic models such as CPSS-Mol, BLAST, and BLAST-Mol have recently been introduced, incorporating cytogenetic and molecular data. Treatment decisions for CMML patients should be comprehensively determined based on prognostic stratification, considering the patient's symptoms, disease burden (manifested as cytopenias or proliferative features) , evidence of disease progression, as well as individual patient status and preferences. This article provides an overview of diagnostic considerations, prognostic assessment and therapeutic options.

To summarize the research in tissue regeneration and engineered scaffold materials for the prevention and treatment of lymphedema.

To review the research progress and application prospects of Kartogenin (KGN) in cartilage repair and tissue engineering.

In current clinical practice, successful kidney transplantation requires lifelong immunosuppression to prevent graft rejection, which is unfortunately associated with significant morbidity, mortality, and reduced quality of life. Over the past 2 decades, there has been growing interest and encouraging progress in clinical therapeutic approaches to transplantation tolerance, defined as stable allograft acceptance in the absence of chronic immunosuppression. To date, these advances have largely been based on the concept of hematopoietic chimerism, achieved by bone marrow or hematopoietic stem cell transplantation performed at the time of solid organ transplant. Recipients undergo a conditioning regimen prior to combined kidney and bone marrow transplantation that allows donor-derived hematopoietic cells to expand persistently or transiently. These clinical trials were based on foundational concepts developed over half a century of preclinical work in mice and large animal models. Preclinical models have also proven essential in addressing unforeseen challenges that arise during clinical trials. In this review, we discuss the foundational basic studies in murine models and preclinical work in large animal models and the current clinical efforts to achieve allograft tolerance in kidney transplantation.

Multiple myeloma, a hematologic malignancy of plasma cells characterized by excessive monoclonal protein production, accounts for 36,000 new cancer diagnoses annually in the United States. The median age at diagnosis is 69 years. Multiple myeloma may present with symptoms, such as bone pain, fatigue, anemia, weight loss, kidney failure, and hypercalcemia, although some patients are asymptomatic. Initial evaluation includes complete blood cell count, comprehensive metabolic panel, serum calcium level, urinalysis, thyroid-stimulating hormone (thyrotropin), urine and serum protein electrophoresis, and radiography of symptomatic bony sites. Diagnosis relies on a combination of urine and serum protein electrophoresis, serum immunofixation, serum free light chain assay, imaging (computed tomography or positron emission tomography-computed tomography), and bone marrow analysis. Oncology referral is recommended if the initial evaluation is suggestive of multiple myeloma. Treatment is determined by a combination of disease characteristics and patient factors and typically involves a three- to four-drug regimen followed by autologous stem cell transplantation if eligible, and then maintenance therapy. Adjunctive care includes bisphosphonates or denosumab and venous thromboembolism prophylaxis. Family physicians play a crucial role in the patient's multidisciplinary team for addressing psychosocial needs, identifying relapse or recurrence, and managing comorbidities.

Hypoxia is an inevitable consequence of surgical interventions such as bone augmentation and soft tissue transplantation in oral and maxillofacial surgery. Cellular adaptation to hypoxic conditions critically influences regenerative processes, including osseointegration, angiogenesis and tissue integration. This systematic review investigated the effects of hypoxic conditions and hypoxia-regulating strategies on tissue regeneration, with the aim of identifying mechanisms to enhance clinical outcomes.

First described by Joseph Paneth in 1888 in the small intestine, particularly in the crypts of Lieberkühn, Paneth cells have since emerged as a critical subtype of intestinal epithelial cells (IECs), which together constitute the body’s largest interface with the external environment, continuously exposed to pathogens, dietary components, and toxins. Paneth cells represent a unique, long-lived secretory IEC population located at the crypt base, where they play indispensable roles in antimicrobial defense and stem cell niche maintenance. Their differentiation, positioning, and survival are governed by tightly regulated signaling networks, including the Wnt and Notch pathway. Although traditionally viewed as terminally differentiated, emerging evidence suggests Paneth cells possess a certain level of plasticity, enabling functional adaptation or dedifferentiation under stress or injury. These characteristics position Paneth cells as central regulators of intestinal homeostasis and epithelial barrier integrity. Over the last decades, accumulating evidence has established that Paneth cell dysfunction is closely linked to microbial dysbiosis and the development of inflammatory bowel disease (IBD), highlighting their contribution to disease pathogenesis. Recent discoveries on how Paneth cell dysfunction contributes to intestinal inflammation are uncovering new therapeutic approaches aimed at reestablishing Paneth cell homeostasis and alleviating IBD progression. In this review, we comprehensively summarize current knowledge on Paneth cell differentiation, function, and their role in gut host defense and epithelial barrier maintenance. We further discuss mechanisms by which Paneth cell dysfunction disrupts intestinal homeostasis, promoting IBD development, and highlight emerging therapeutic strategies that target Paneth cells to reestablish barrier integrity and restore gut health.

Arterial regeneration represents a critical frontier in cardiovascular medicine, as progressive endothelial dysfunction, maladaptive vascular smooth muscle cell (SMC) plasticity, and chronic inflammation drive atherosclerosis, restenosis, and vascular aging. Although current therapies such as pharmacological risk-modifying therapies and interventional revascularization procedures mitigate the risk and delay the progression, they are still unable to restore vascular integrity. Stem cell-based strategies were initially conceived to replace the lost vascular cells directly; however, accumulating evidence indicates their therapeutic benefits arise from paracrine mechanisms including regulation of endothelial repair, modulation of SMC phenotypic switching, and attenuation of inflammatory signaling. This paradigm shift has expanded the regenerative landscape to encompass endothelial progenitor cells, mesenchymal stromal cells, induced pluripotent stem cell-derived vascular lineages, and engineered extracellular vesicle platforms. Parallel advances in biomaterials, mechanically tuned scaffolds, and hybrid cell-matrix constructs provide more physiologic microenvironments for vascular repair and enhance the retention, potency, and safety of regenerative therapies. Concurrently, gene editing, metabolic reprogramming, and hypoxic preconditioning further refine the functional capacity of stem cell-derived products, enabling targeted correction of endothelial instability and improving regulation of vascular remodeling. Integration of multi-omic profiling and high-resolution vascular phenotyping now positions the field to align regenerative strategies with patient-specific determinants of disease. This review integrates current knowledge on stem cell-mediated endothelial regeneration, SMC phenotype regulation, and bioengineered vascular interventions, and examines emerging precision-medicine frameworks poised to guide next-generation therapies that link mechanistic principles with translational progress to enable durable restoration of arterial structure and function, and long-term vascular health, thereby providing a theoretical basis for future research.

Increased life expectancy across developed countries has highlighted the personal and societal value of healthy ageing. A well-functioning neuromuscular system is fundamental to quality of life and functional independence. The systemic deterioration of tissue and organ function during ageing is reflected in the diverse cellular and molecular mechanisms implicated in the age-related loss of muscle mass and strength and its extreme form, termed sarcopenia. Proposed contributors include neurodegeneration, impaired proteostasis, deficient regeneration, systemic hormonal decline, chronic inflammation, and dysregulation of muscle-resident cell populations such as muscle stem cells, fibro-adipogenic progenitors and immune cells. Recent efforts have added granularity to our understanding of the molecular response of muscle to ageing and started to unravel the cellular origins of these signals. Advancements in cell-targeting strategies (e.g. AAV capsids and antibody-targeted therapeutics) are opening new avenues for targeted interventions. Nonetheless, this raises the salient question - what should treatments for age-related muscle wasting target? While anabolic and catabolic signalling within muscle fibres has been the primary target of strategies to counteract age-related muscle loss, these efforts may be futile if impairment in other cell types such as muscle stem cells and motor neurons drive the wasting process. Furthermore, individual differences in activity, nutrition, sex, comorbidities and genetics are likely to influence the predominant mechanisms driving age-related muscle wasting. This multifactorial condition may therefore require a multifactorial solution, with scientists focusing on diverse causal mechanisms to identify and develop effective interventions.

Degenerative eye diseases are major causes of irreversible vision loss worldwide, but effective treatments remain limited, partly due to the lack of effective human models. Retinal organoids derived from stem cells can recapitulate key structural and physiological features of the human retina, offering powerful tools to study disease mechanisms and develop new therapies. Here, we review recent progress in engineering retinal organoids and eye-on-a-chip models for modeling degenerative eye diseases, with a focus on engineering innovations. We first describe conventional methods for organoid differentiation and characterization along with current outstanding challenges. To better engineer retinal organoids, new strategies that leverage microfluidics and biomaterials have emerged to regulate dynamic and physiologically relevant environments for organoid differentiation. Moreover, the integration of artificial intelligence, multimodal sensing, and data analytics improves the monitoring and prediction of retinal function and therapeutic outcomes. Finally, we discuss future directions in innovating next-generation retinal organoid and eye-on-a-chip models for disease modeling, drug discovery, and vision restoration, highlighting their potential for precision ophthalmology.

Redox homeostasis is crucial for maintaining cellular processes and is closely linked to human skeletal health. Prior research has demonstrated that oxidative stress is important for regulating osteoblast and osteoclast differentiation in the bone microenvironment, leading to a reduction in bone mass and skeletal degradation. The bone marrow is a complex niche containing various cell types, including bone marrow adipocytes (BMAs), which engage in dynamic interplay with osteo-associated cells through processes governed by redox equilibrium within the marrow compartment. During aging, a decrease in osteoblasts coincides with an increase in BMAs counts. Evidence suggests that oxidative stress influences the differentiation of BMAs, leading to the accumulation of bone marrow adipose tissue (BMAT) and contributing to bone remodeling imbalances. The fate of BMAs is determined by a precise molecular network that involves transcription factors, epigenetic regulators, and ncRNAs. The expansion of BMAT affects the commitment and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), resulting in poor osteoblast differentiation, enhancing osteoclast differentiation and function, and accelerating bone loss. Consequently, elucidating oxidative stress dynamics in pathological marrow states and delineating their correlation with aberrant BMAs differentiation emerges as a research imperative. This comprehensive review delineates the mechanistic interplay whereby oxidative stress within the osseous niche orchestrates BMAs differentiation, while simultaneously exploring how expanded BMAs reciprocally amplify oxidative stress levels. Furthermore, we dissect how maladaptive BMAs differentiation cascades perturb osteoblast-osteoclast equilibrium through paracrine signaling and microenvironmental reprogramming. By synthesizing these molecular insights, we aim to unravel the pathogenic nexus between BMAs-driven redox imbalance and compromised bone remodeling, ultimately proposing innovative therapeutic strategies for osteopathic disorders. The translational potential of this article: The growing interest in BMAs originates from their significant yet underexplored functions in bone metabolism and systemic energy homeostasis, establishing them as a novel and promising component for managing osteoporosis and related metabolic bone disorders. Clinically, this focus addresses two critical gaps in current osteoporotic care, which predominantly relies on anti-resorptive agents and bone-forming medications. While these conventional treatments demonstrate efficacy, they face limitations such as potential long-term safety concerns, the presence of treatment-resistant patients, and an incomplete ability to restore bone quality and mechanical strength. Targeting BMAs presents a complementary or alternative therapeutic strategy by addressing a fundamental cellular element within the bone marrow microenvironment that actively participates in bone remodeling. Mastering the regulation of BMAs enables a shift toward a more comprehensive "whole-bone" therapeutic approach, aiming not merely to increase bone mineral density but also to enhance bone quality and fracture healing, thereby fundamentally addressing the pathogenesis of skeletal fragility in aging populations and pathological conditions characterized by aberrant marrow fat accumulation.

Myeloid-derived suppressor cells (MDSCs) are a diverse group of immature myeloid cells critically involved in establishing an immunosuppressive environment within tumors. They impede effective anti-tumor immune responses through multiple mechanisms, including metabolic reprogramming, cytokine secretion, and immune checkpoint ligand expression. This immunosuppressive activity enables tumor progression and resistance to therapies, including immunotherapy. Recent advances reveal that targeting the metabolic pathways of MDSCs can impair their suppressive functions, offering promising strategies to enhance anti-cancer immunity. Approaches such as metabolic inhibition, direct depletion, blockade of recruitment and expansion, and promotion of differentiation into mature immune cells are under active investigation. Combining these strategies with immune checkpoint inhibitors and cell-based therapies, such as cancer vaccines and adoptive T-cell or NK-cell therapies, holds significant potential for overcoming immune resistance. Nonetheless, challenges including MDSC heterogeneity, toxicity, and biomarker validation must be addressed to optimize clinical translation. This review comprehensively covers current insights into the immune-metabolic mechanisms underpinning MDSC-mediated immunosuppression in the tumor microenvironment. It explores emerging therapeutic strategies aimed at targeting MDSCs through metabolic interventions, depletion, and modulation of their recruitment and differentiation. Furthermore, it discusses the integration of MDSC-targeted approaches with existing immunotherapies, highlights ongoing clinical trials, and assesses future directions, such as personalized, biomarker-driven treatments. Ultimately, this review underscores the potential of MDSC-focused therapies to significantly improve the efficacy of cancer immunotherapy and overcome mechanisms of tumor immune evasion.

Systemic Lupus Erythematosus (SLE) is a chronic immune-mediated inflammatory disease characterized by dysregulated immune tolerance, abnormal secretion of autoantibodies, and multi-organ damage. Among them, mutations in genetic susceptibility genes, abnormal epigenetic modifications, excessive oxidative stress, abnormal accumulation of inflammatory factors, and intestinal flora disorders are all key specific factors that lead to immune dysfunction, abnormal production of autoantibodies, and multi-organ damage in patients with SLE. The bone marrow microenvironment, as a key niche for immune cell development, plays a pivotal role in the pathogenesis of SLE, especially through the metabolic reprogramming of bone marrow mesenchymal stromal cells (BMSCs). Recently, studies have demonstrated that under the influence of the bone marrow microenvironment, BMSCs can undergo metabolic reprogramming, regulated by the aforementioned abnormal factors related to SLE, the key metabolic pathways such as glucose metabolism, lipid metabolism and mitochondrial metabolism are disrupted, thereby affecting their regulatory functions on various immune cells. This process plays a role in the development and progression of immune-mediated inflammatory diseases like SLE. This article provides a comprehensive review of the current knowledge regarding the metabolic regulatory mechanism of the BMSCs on the immune cells in SLE and discusses recent advances in clinical translation.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a myeloid bias in hematopoietic stem/progenitor cells, aging of bone marrow mesenchymal stem cells (BMSCs) with a tendency toward differentiation into the adipocyte lineage, an imbalance of key immune cell subpopulations such as M1 and M2 macrophages and Th17 and regulatory T cells (Treg), as well as remodeling of cytokine and chemokine axis networks. Signaling pathways such as RANK/RANKL/OPG, Wnt/β-catenin, CXCL12-CXCR4, and S1P - along with systemic factors like estrogen deficiency, inflammatory aging, and the gut-bone-immune axis-collectively shape the characteristic bone immune microenvironment of PMOP. Based on this, this article systematically reviews the changes in cell lineage and molecular mechanisms underlying PMOP bone marrow immune reprogramming. It focuses on the key signaling networks in the bone immune microenvironment and their relationship with the mechanisms of existing anti-osteoporosis drugs. Furthermore, it proposes an immunotherapy approach represented by a three-tiered framework: traditional bone-targeted drugs, immune-guided therapy, and comprehensive intervention of the bone marrow microenvironment. Finally, in conjunction with emerging technologies such as multi-omics, single-cell, and spatial omics, this article discusses future directions for constructing a PMOP bone immune map and achieving precise stratification and individualized intervention, aiming to provide a theoretical basis and methodological reference for mechanistic research and bone immune-targeted therapy of PMOP.

The oral cavity serves as the primary source of oral mesenchymal stem/progenitor cell populations residing in the dental pulp, periodontal ligament, deciduous tooth pulp, and gingival connective tissue. Oral and periodontal tissues exist in a constantly loaded biomechanical environment, where forces from mastication, vascular pulsation, and orthodontic manipulation continuously act on resident mesenchymal stem cells, including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from human exfoliated deciduous teeth (SHEDs), and gingival mesenchymal stem cells (GMSCs). In this review, we use the term "oral stem cells" to specifically denote oral mesenchymal stem/progenitor populations residing in dental pulp, periodontal ligament (PDL), deciduous tooth pulp, and gingival connective tissue (DPSCs, PDLSCs, SHEDs, and GMSCs), which are most relevant to orthodontic remodeling and dento-periodontal regeneration. For clarity, this review highlights the defining characteristics, representative markers, differentiation potential, and immunomodulatory properties of these oral stem cells within the manuscript, establishing a foundation for understanding how mechanical forces shape their fate. These forces are not merely physical stimuli; they actively reshape stem cell fate by engaging a multilayered mechano - epigenetic regulatory network that integrates cytoskeletal mechanotransduction, nuclear mechanics, and chromatin remodeling. Mechanical inputs such as compression, tension, shear stress, and extracellular matrix stiffness modulate DNA methylation, histone acetylation and methylation, 3D genome architecture, and non-coding RNA programs. These epigenetic and epitranscriptomic adaptations stabilize lineage commitment, influence inflammatory and regenerative outputs, and may establish "mechanical memory" that persists after load removal. Metabolic rewiring, including YAP/TAZ- and MAPK-driven control of mitochondrial activity and metabolite pools, provides an additional axis linking mechanics to chromatin state. Building on these mechanisms, emerging therapeutic strategies aim to couple defined mechanical cues with epigenetic modulators and mechano-tunable biomaterials to enhance pulp regeneration, periodontal repair, and orthodontic bone remodeling with higher precision. The review further highlights single-cell multi-omics and live-cell imaging approaches as essential tools to resolve force-dependent chromatin dynamics in vivo, and proposes that integrating biomechanics, epigenetics, and metabolic control will enable next-generation regenerative dentistry and personalized orthodontic intervention.

Knee osteoarthritis (KOA) remains a leading cause of disability, and mesenchymal stem cells (MSCs) show potential for KOA treatment. However, existing studies demonstrate conflicting results on the optimal dose and tissue source of MSCs for KOA treatment. This gap limits evidence-based treatment decisions.

Tendon injuries are common musculoskeletal conditions that affect both athletic and working populations. Although surgical intervention remains the mainstay of treatment for large tendon injuries, conventional approaches often result in suboptimal healing and functional outcomes. Recent evidence has shown that stem cell therapy may play a role in the management of these injuries. This review comprehensively examines the current literature on stem cell applications in tendon regeneration by analyzing both preclinical and clinical evidence. Specifically, we evaluated various stem cell populations, their characteristics, delivery mechanisms, and repair processes. Additionally, we addressed the limitations of stem cell-based therapies while highlighting emerging trends and future research directions in this rapidly evolving field.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is characterized by chronic mucosal inflammation driven by dysregulated interactions between intestinal epithelial cells (IECs) and immune components. This review systematically explores the dynamic interplay between epithelial barrier integrity and immune-microenvironmental regulation in IBD pathogenesis. We highlight the dual roles of innate immunity (neutrophils, macrophages, dendritic cells, and innate lymphoid cells) and adaptive immunity (Th1, Th17, and Treg cells) in orchestrating inflammatory cascades and mucosal repair. It also describes the interaction between microbial metabolites and the intestinal microenvironment.Key mechanisms include neutrophil extracellular trap (NET)-mediated epithelial damage, macrophage polarization modulated by ROS/NOX4 signaling, and IL-22/STAT3-driven epithelial regeneration. Additionally, we dissect the Wnt/β-catenin and bile acid-TGR5 (Takeda G-protein-coupled receptor 5) pathways in intestinal stem cell renewal. Emerging therapeutic strategies targeting epithelial-immune axes, such as anti-IL-23/IL-17 biologics and MSC-derived exosomes, are critically evaluated. By integrating recent advances in single-cell omics and preclinical models, this review underscores the necessity of precision medicine approaches to restore immune-epithelial homeostasis. This paper also introduces the current application of organoids-a novel emerging technology-in experimental research.Future research should prioritize spatial-temporal mapping of cellular interactions and leverage organoids to advance translational validation of dual-target therapies to bridge mechanistic insights into clinical practice.