Cell Transplantation最新文献

Chronic active Epstein-Barr virus (CAEBV) infection is a rare and highly lethal lymphoproliferative disorder. The pathological basis of this condition involves Epstein-Barr virus (EBV) persisting in hematopoietic stem cells, driving clonal expansion of T cells or natural killer (NK) cells, and subsequently triggering systemic inflammatory responses and multi-organ failure. Current treatment modalities, encompassing antiviral medications, immunosuppressants, and cytotoxic chemotherapy, offer only transient remissions, with the majority of patients ultimately experiencing relapse. Recent single-cell sequencing and chimera studies have confirmed that EBV-infected hematopoietic stem cells constitute the "seed" cell population for CAEBV initiation and maintenance. This finding indicates that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment known to date that can fully eradicate viral reservoirs and restore normal immunity, suggesting that it may represent a curative strategy. Nevertheless, transplantation timing, donor matching, conditioning intensity, and transplant-related complications have been shown to have a significant impact on long-term prognosis. The clinical decision-making process necessitates a high degree of individualization, incorporating molecular risk factors, disease activity, and comorbidities. Advancing research into the latent-lytic cycle regulation mechanisms of EBV, in addition to the clinical translation of small-molecule inhibitors targeting viral proteins and EBV-specific adoptive cell therapies, holds great promise for the future. One such potential avenue for future research is the development of an integrated "pre-transplant viral load reduction-post-transplant relapse prevention" strategy. This approach shows great potential in reducing transplant-related mortality and continuously improving survival outcomes for CAEBV patients.

Recent years have witnessed rapid advancements in 3D bioprinting and the widespread application of mesenchymal stem cells (MSCs) across various medical disciplines. The synergistic integration of 3D bioprinting and MSCs has opened innovative avenues for tissue engineering and regenerative medicine, particularly in bone tissue repair and regeneration. However, the progress of 3D bioprinting in the field of MSCs research still requires further exploration, and there remains a scarcity of related bibliometric analyses in this domain. With the aim of addressing this existing gap, this research systematically searched the Web of Science Core Collection for publications spanning from January 2003 to October 2025. It employed CiteSpace for cluster and evolution analysis, VOSviewer for collaboration network and keyword co-occurrence analysis, and the R package "bibliometrix" for statistical evaluation of bibliometric indicators. This bibliometric analysis focused on tissue engineering research integrating 3D bioprinting with MSCs, encompassing 1,846 original articles. These articles were authored by 10,276 researchers from 2,024 institutions across 69 countries and published in 342 academic journals. From 2014 to 2023, the number of annual publications exhibited a fluctuating yet rapid upward trend. China and the United States emerged as the most influential countries, with China experiencing a particularly substantial increase in research output-though international collaborations among institutions and authors remained limited. Wu C.T. and Bose S. stood out as key contributors to this field, while journals such as Biomaterials and Biofabrication have significantly advanced the discipline. High-frequency keywords including "3D printing" and "tissue engineering" reflected the core research directions, whereas emerging terms such as "MSC-EVs" and "nanocomposites" indicated current frontiers; in addition, "bioink," "3D scaffold," "osteogenesis," and "angiogenesis" represented areas gaining growing research attention. Overall, this bibliometric study provides a thorough overview of the research tendencies and developments related to 3D bioprinting in the MSC field.

Diabetes mellitus (DM) is a metabolic disorder with chronic hyperglycemia due to insulin deficiency and/or impaired insulin action. DM is a common disease, but it often threatens a patient's quality of life. Cellular replacement therapy using insulin-producing cells is a promising therapy for severe DM because of the proper provision of internal insulin according to a change in blood glucose concentrations. This Special Collection, "Cellular Replacement Therapy for Diabetes," was planned to appeal the current status and present novel translational trials of this therapy. Ten specialists presented their research, which attempted to overcome three limitations of the current cellular replacement therapy, including the regulation of immunity, limited donor supplies, and establishment of a preferable transplant site for cellular replacement therapy. Regarding regulation of immunity, potential of mesenchymal stem cells and immunomodulatory splenocytes is clarified. Regarding alternative donors, the current status of porcine islet xenotransplantation and therapy using multipotent stem cell-derived cells is introduced. And regarding transplant site, possibility of liver surface and subcutaneous tissue is elucidated.

Mesenchymal stem cells (MSCs) are recognized for their capacity to modulate immune responses, including those directed against tumors. In this study, we investigated the temporal effects of MSCs administration on anti-tumor immunity in a murine 4T1 breast cancer model. BALB/c mice were intraperitoneally injected with MSCs either 24 h (MSC1d) or 14 days (MSC14d) after orthotopic implantation of 4T1 mammary carcinoma cells. Early MSC administration (MSC1d) exhibited changes in immune cell phenotypes consistent with enhanced antitumor potential, including increased activity of natural killer (NK) cells, dendritic cells (DCs), macrophages, and T lymphocytes. These immunological changes correlated with reduced tumor growth and prolonged survival. Mice in the MSC1d group exhibited elevated serum levels of pro-inflammatory and anti-tumor cytokines (TNF-α, IFN-γ, IL-6, and IL-17), alongside decreased concentrations of immunosuppressive cytokines (TGF-β and IL-10). Tumor tissue analysis revealed increased infiltration of NK cells expressing markers associated with antitumor activity (IFN-γ-producing CD178⁺), CD80⁺/CD86⁺/I-A⁺ TNF-α-producing DCs, Th1-type CD4⁺ T cells, and Granzyme B-expressing CD8⁺ cytotoxic T lymphocytes (CTLs). Additionally, spleens of MSC1d-treated mice displayed significantly elevated populations of CD11c⁺ DCs, TNF-α/IFN-γ-secreting NK cells, CD4⁺ Th1 and Th17 cells, and CD8⁺ CTLs expressing markers associated with cytotoxic function (TNF-α, IFN-γ, and IL-17). Conversely, late MSCs administration (MSC14d) was associated with immunosuppression. Tumors from MSC14d-treated mice showed a decreased presence of IFN-γ⁺ and IL-17⁺ NK1.1⁺ cells, F4/80⁺ macrophages, IL-12⁺ DCs, and cytotoxic T cells. Spleens from these mice revealed a significant expansion of regulatory T cell (Treg)-like populations, including CD25⁻, FoxP3⁻, CD25⁺FoxP3⁻ cells, and TGF-β/IL-10-producing CD3⁺ and CD4⁺ T cells. Furthermore, serum levels of immunosuppressive mediators TGF-β and vascular endothelial growth factor (VEGF) were significantly elevated in the MSC14d group. Collectively, these findings demonstrate that the immunomodulatory effects of MSCs on breast cancer are highly dependent on the timing of their administration. Mesenchymal stem cells delivered during early tumor development enhance phenotypes consistent with antitumor potential and suppress tumor progression, whereas administration during later stages promotes immune evasion and tumor growth.

This systematic review examines emerging delivery systems for bioactive molecules within regenerative endodontic therapy (RET) where hydrogels, nanogels, and polymeric nanoparticles along with advanced nanocarriers such as liposomes aquasomes, vesosomes, and mesoporous silica nanoparticles form the primary focus. The extensive literature search in PubMed, Scopus, and Web of Science databases (until August 2025) yielded a total of 47 eligible articles, including in vitro, ex vivo, animal, and a few clinical studies. Hydrogels emerged as a significant category, showcasing enhanced regenerative effects when used for the sustained release of various growth factors such as transforming growth factor-beta (TGF-β₁), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF). This was associated with improved angiogenesis and odontogenic differentiation. Nanogels exhibited high protein-loading efficiency and facilitated the differentiation of dental pulp stem cells, while polymeric nanoparticles demonstrated prolonged antibiotic and growth factor delivery with lower cytotoxicity. Among advanced nanocarriers, mesoporous silica nanoparticles showed promising potential for controlled release of growth factors and the formation of pulp-like tissues in animal models. In summary, the selected platforms for the delivery of bioactive molecules within RET show significant promise in terms of enhancing cell viability, bioactivity, and tissue regeneration. The findings indicate a practical pathway for clinicians aiming to achieve successful pulp-dentin tissue regeneration through translation research.

Autoimmune diseases (AIDs) are a class of diseases caused by autoimmune intolerance, which can be divided into systemic and organ-specific diseases. AIDs affect approximately 10% of the global population and rank among the leading causes of disability and mortality. At present, immunosuppressive agents are the first choice for the treatment of AIDs. B-cell-targeted therapies-particularly CD20 monoclonal antibodies-have brought new hope for systemic AIDs, yet a subset of patients still respond poorly. As a rapidly developing cellular immunotherapy technology, Chimeric antigen receptor T cell (CAR-T) plays an important role in the treatment of hematological malignancies. CAR-T targeting B-cell-specific antigens can rapidly deplete circulating B cells, thereby reducing the formation of autoantibodies, which has become the basis for research on CAR-T in the treatment of autoimmune diseases. Currently, many studies are underway, and CAR-T and its derivative therapies bring new hope for the treatment of autoimmune diseases.

Donor-derived recipient-specific anti-HLA antibodies (RSAs) are rarely investigated in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective study, 185 haploidentical donor-recipient pairs were consecutively analyzed. Anti-HLA antibodies were detected in eight donors (4.3%) and 31 recipients (16.8%), with only one donor (0.5%) harboring RSAs. Donors were predominantly young, male, and transfusion-naïve, which likely contributed to the low antibody prevalence. No association was observed between donor antibody positivity and graft rejection or severe acute graft-versus-host disease (GVHD). However, recipients of antibody-positive grafts showed higher rates of Epstein-Barr virus (EBV) reactivation and transfusion refractoriness. Our findings suggest that donor-derived HLA antibodies, particularly RSAs, are infrequent and clinically limited under current haploidentical donor selection and immunosuppressive strategies, but may subtly influence post-transplant immune recovery.

The global shortage of human donor livers poses a formidable barrier to treating end-stage liver diseases and unresectable hepatic malignancies, leaving millions of patients without life-saving options each year. While genetically engineered pig-to-human xenotransplantation has achieved significant breakthroughs in cardiac and renal fields, liver xenotransplantation has long lagged due to the liver's intricate metabolic, synthetic, and immunological functions. The recent report by Zhang et al. in the Journal of Hepatology-documenting the world's first successful auxiliary liver xenotransplantation from a 10-gene-edited pig to a living human, with the recipient surviving 171 days-marks a transformative milestone in regenerative medicine. This commentary examines the study's groundbreaking contributions to donor genetic engineering and perioperative clinical management, while critically analyzing the persistent challenge of xenotransplantation-associated thrombotic microangiopathy and outlining future directions to advance clinical translation.