Cell Transplantation最新文献

The differentiation of adipose-derived stem cells (ADSCs) into tendon cells is a key process in tissue engineering and regenerative medicine. The Wnt signaling pathway plays a key role in regulating cell fate and tissue-regeneration decisions, making it a promising target for improving tendon differentiation. Photobiomodulation (PBM) is a non-invasive therapeutic approach that has been shown to modulate cellular processes, including stem cell differentiation. The aim of this review is to provide an understanding of the effects of PBM and Wnt signaling on ADSC differentiation. The complexities of interactions between PBM and dynamic Wnt pathway exist in different ways during the differentiation of ADSCs into tendon cells. The results highlight the potential therapeutic application of PBM in promoting tendon healing and regeneration. This review explores the clinical importance of PBM-mediated Wnt signaling regulation in tendon injuries. The results of this review will provide valuable information for the rational design of therapeutic strategies to enhance tendon differentiation and improve clinical outcomes and will also contribute to increasing knowledge of the synergistic relationship between PBMs, Wnt signaling pathways, and stem cell differentiation.

Coronary artery bypass grafting (CABG) involves creating new conduits to restore blood flow to the heart. Using autologous vascular grafts presents challenges, including infection risk after vein harvesting, and scarcity of viable vein tissue. Researchers are exploring tissue-engineered vascular grafts (TEVGs), aiming to create optimal small-diameter vascular graft (SDVG) (<6 mm) for CABG surgery. TEVGs with suitable long-term patency could offer a promising alternative, potentially reduce patient morbidity and improve surgical outcomes. However, no SDVG is commercially available for CABG surgery in Europe, and no new clinical trials of coronary TEVGs have been reported since 2018. This narrative review summarizes the development and use of SDVG (<6 mm) for CABG, focusing on TEVGs and cell-seeding strategies. We outline the main types of grafts tested in preclinical and early clinical studies and highlight how different cell sources and seeding approaches aim to enhance graft functionality, patency, and long-term outcome.

Tissue repair is an extremely crucial part of clinical treatment. During the course of disease treatment, surgery, chemotherapy, and radiotherapy cause tissue damage. On the other hand, Normal tissue from accidental or therapeutic exposure to high-dose radiation can cause severe tissue damage. There is an urgent need for developing medical countermeasures against radiation injury for tissue repair. Tissue repair involves the regeneration, proliferation, differentiation, and migration of tissue cells; imbalance of local tissue homeostasis, progressive chronic inflammation; decreased cell activity and stem cell function; and wound healing. Although many clinical treatments are currently available for tissue repair, they are expensive. The long recovery time and some unavoidable complications such as cell damage and the inflammatory reaction caused by radiotherapy have led to unsatisfactory results. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have similar tissue repair functions as MSCs. In tissue damage, EVs can be used as an alternative to stem cell therapy, thereby avoiding related complications such as immunological rejection. EVs play a major role in regulating tissue damage, anti-inflammation, pro-proliferation, and immune response, thus providing a diversified and efficient solution for the repair of disease- and radiotherapy-induced tissue damage. This article reviews the research progress of mesenchymal stem cell-derived EVs in promoting the repair of tissue including heart, lung, liver, intestine, skin, blood system, central nervous system, and tissue damage caused by radiotherapy, thereby aiming to offer new directions and ideas for the radiotherapy and regenerative applications.

With the rising demand for liver transplantation (LT), research on acute rejection (AR) has become increasingly diverse, yet no consensus has been reached. This study presents a bibliometric and latent Dirichlet allocation (LDA) topic modeling analysis of AR research in LT, encompassing 1399 articles. The United States, Zhejiang University, and the University of California, San Francisco emerged as leading contributors, while Levitsky J and Uemoto SJ were key researchers. The most influential journals included the American Journal of Transplantation, Journal of Hepatology, and Transplantation. The analysis reveals a transition from traditional histological assessments to molecular diagnostics, genetic and epigenetic profiling, and noninvasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) and microRNAs. Advances in immune checkpoint inhibitors (ICIs), cell-based therapies (Tregs, mesenchymal stem cells (MSCs)), AI-guided immunosuppression, and nanoparticle-mediated drug delivery systems reflect a growing emphasis on precision medicine. In addition, recent exploration of microbiome-based therapies and regenerative medicine, including MSCs and their extracellular vesicles, offers promising new avenues for reducing long-term immunosuppressive drug dependency and enhancing graft survival. These developments not only improve early AR detection and personalized treatment but also reduce toxicity, foster immune tolerance, and expand the scope of individualized therapeutic options. Global collaboration, supported by cutting-edge research and AI-driven decision-making, remains essential for refining AR strategies, improving graft survival, and achieving better long-term patient outcomes.

Pancreatic islet transplantation (PITx) is a promising treatment option for patients with type 1 diabetes mellitus. Previously, we demonstrated that therapy with alloantigen-specific immunomodulatory cells (IMCs) generated ex vivo in the presence of anti-CD80 and CD86 monoclonal antibodies (mAbs), successfully induced tolerance following clinical liver transplantation. To extend IMC therapy to PITx, it is crucial to address the strong inflammatory and innate immune responses that occur immediately after PITx. In this study, we investigated the efficacy of IMCs in modulating macrophage activation and mitigating inflammatory damage of pancreatic islets. IMCs were induced using mouse splenocytes in the presence of anti-mouse anti-CD80 (RM80) and anti-CD86 (GL-1) mAbs. IMCs exerted donor-specific immunosuppressive effects in a mixed lymphocyte reaction. During lipopolysaccharide (LPS) stimulation, the addition of IMCs suppressed conversion to the M1 phenotype and promoted a shift toward the M2 phenotype, particularly under direct cell-cell contact conditions. Nitric oxide production, a hallmark of M1 polarized macrophages, was significantly reduced in LPS-stimulated RAW264 macrophages by IMC treatment. These findings were associated with reduced secretion of pro-inflammatory cytokines, tumoral necrosis factor α, and interleukin-6, and increased interleukin-10 production by macrophages. IMCs effectively prevented macrophage-mediated islet destruction after 12 h of co-culture with LPS-stimulated macrophages and significantly inhibited macrophage migration toward allogeneic islets in vitro. Intraportal co-infusion of IMCs with syngeneic islets in a mouse PITx model resulted in reduced messenger RNA (mRNA) expression of pro-inflammatory cytokines in the recipient liver. Immunohistochemical staining revealed a significantly lower number of F4/80+ macrophages at the transplantation site in IMCs-treated mice. These results demonstrate that IMCs modulate macrophage polarization, promoting a shift toward the M2 phenotype and protecting islets from macrophage-mediated damage. These effects combined with its intrinsic donor antigen-specific immunosuppressive capacity make IMC therapy a promising strategy for improving outcomes after PITx.

The Japanese monkey has been used in several animal studies; however, its potential as a recipient model for xenotransplantation is unclear. The potential of the Japanese monkey as a recipient for xenotransplantation was assessed using two experimental models. The first model evaluated the optimal dose of tacrolimus without severe adverse events. The plasma tacrolimus levels, blood counts, and hepatic and renal function tests were evaluated. The second model assessed the immunosuppressive effects of thymoglobulin and tacrolimus. Immunosuppression was evaluated using blood counts and flow cytometry to measure lymphocytes in peripheral blood mononuclear cells (PBMCs). In the first model, the target trough level (10-15 ng/ml) was achieved and maintained with tacrolimus administration at 1.6 mg/kg/day in all monkeys. There were no adverse events related to the blood count or to liver, kidney, or nutrient parameters at this dose, except for hemoglobin. In the second model, a decrease in white blood cells was observed. Flow cytometry revealed a temporary decrease in T- and B-cell numbers among PBMCs on day 4. We consider that the Japanese monkey is acceptable to be used as a recipient model for preclinical xenotransplantation. The safe administration of tacrolimus and thymoglobulin is clarified for this model.

The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions. This protection is ensured by the production of a variety of immunosuppressive molecules, which create the immune privilege of the eye. In addition, ocular cells are potent producers of numerous growth and trophic factors which support the survival and regeneration of diseased and damaged cells. If the immune privilege of the eye is interrupted and the regulatory mechanisms are not sufficiently effective, the eye disease can progress and result in worsening of vision or even blindness. In such cases, external immunotherapeutic interventions are needed. One perspective possibility of treatment is represented by mesenchymal stromal/stem cell (MSC) therapy. MSCs, which can be administered intraocularly or locally into diseased site, are potent producers of various immunoregulatory and regenerative molecules. The main advantages of MSC therapy include the safety of the treatment, the possibility to use autologous (patient's own) cells, and observations that the therapeutic properties of MSCs can be intentionally regulated by external factors during their preparation. In this review, we provide a survey of the immunoregulatory and regenerative mechanisms in the eye and describe the therapeutic potential of MSC application for corneal damages and retinal diseases.

A significant proportion of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) exhibit no response to chimeric antigen receptor (CAR) T-cell therapy or suffer from disease progression thereafter. This study investigated the efficacy and safety of salvage therapy with PD-1 inhibitor-based combination treatment and the patient selection after their CAR T-cell therapy. Twenty-one patients with R/R DLBCL and a high tumor burden were treated with CAR T-cell therapy, a treatment that has shown promising results in clinical trials and has been approved by the Food and Drug Administration (FDA) for use in DLBCL. Patients who achieved complete response (CR) with the CAR T-cell therapy received salvage therapy when their disease progressed again. Patients who obtained partial response (PR) or stable disease (SD) with the CAR T-cell therapy received salvage therapy immediately. Salvage therapy consisted of single PD-1 inhibitors or PD-1 inhibitors combined with chemotherapy. We observed the overall response rate (ORR), overall survival (OS), CAR T-cell amplification, the expression of PD-1, CD3+ T cells, cytokines, and the adverse events. For instance, in a clinical trial of LCAR-B38M CAR T-cell therapy, an 88% ORR was observed, with 74% of patients achieving CR and a median duration of response (DOR) of 16 months. The ORR and CR of the salvage therapy were 28.57% and 19.05%, respectively. The ORR and CR were 38.46% and 30.77% in the 13 patients who achieved PR/SD with the CAR T-cell therapy and received salvage therapy 2 months after CAR T-cell infusion. But the ORR and CR were only 12.5% and 0%, respectively, in patients who achieved CR with the CAR T-cell therapy and received salvage therapy when they experienced disease re-progression. The ratio of CAR-T cells on day 7/day 14 was lower in the PR in CAR-T (effective to PD-1) group. Before salvage therapy, the percentage of CD3+ T cells was higher in the PR in CAR-T (effective to PD-1) group. There was no difference in the Common Terminology Criteria for Adverse Events (CTCAE) grades among the four groups in the salvage therapy. PD-1 inhibitor-based salvage therapy in patients with R/R DLBCL following the CAR T-cell therapy could be an effective and safe treatment, especially in patients who achieved PR after the CAR T-cell therapy and received this salvage therapy immediately.Trial registration number: ChiCTR1800019622 and ChiCTR1900025310.

This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including alcoholic, hereditary, idiopathic, Oddi dysfunction, and pancreatic divisum compared to healthy controls. The overall expression of LAMA5 positively correlated with expression of the ECM proteins pan-laminin (R = 0.63, P < 0.001), collagen IV (R = 0.67, P < 0.001), and Perlecan (R = 0.71, P < 0.001). Increased LAMA5 expression was observed within islet endothelial vascular tissue and the peri-islet basal membrane. Increased LAMA5 expression in the pancreas correlated with poor islet isolation yield and posttransplant islet function after 3 months. Increased endothelial expression of LAMA5 and ECM proteins is indicative of progressive damage to the pancreas and correlates with poor graft function after TPIAT.

Adipocyte dysfunction plays a critical role in the pathogenesis of metabolic diseases, including type 2 diabetes (T2D). Human induced pluripotent stem cells (hiPSCs) offer a powerful platform for generating white, beige, and brown adipocytes, supporting both disease modeling and therapeutic research. This review provides a comprehensive summary of current differentiation methods to produce three functionally mature adipocyte types from pluripotent stem cells (PSCs), including forced gene expression techniques, developmental biology-inspired approaches, and advanced three-dimensional (3D) culture systems that enhance cellular maturity and functional relevance. PSC-derived white adipocytes contribute to modeling adipocyte dysfunction not only in conditions such as insulin resistance, lipodystrophy, and premature aging but also in more complex metabolic diseases, including T2D, facilitating the investigation of disease mechanisms and the identification of novel therapeutic targets. In addition, iPSC-based models provide a robust platform for exploring genetic regulation by genome-wide association studies (GWAS)-identified variants through population genetics. This review also evaluates the therapeutic potential of iPSC-derived white, beige, and brown adipocytes in cell transplantation therapy for metabolic diseases, with a focus on engraftment potential and metabolic improvement. Enhancing the maturity and subtype specificity of PSC-derived adipocytes is expected to accelerate the development of personalized medicine and innovative therapeutic strategies for metabolic diseases.