Cell Transplantation最新文献

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread immune dysregulation and systemic inflammation. Among its many manifestations, lupus nephritis (LN) stands out as one of the most severe and life-threatening complications, affecting up to 60% of SLE patients. LN primarily results from a type III hypersensitivity reaction in which immune complexes are deposited within the kidney. This leads to progressive glomerular and tubulointerstitial lesions compromising renal function. A significant portion of patients presenting with LN will progress to end-stage renal disease (ERSD). Despite advances in treatment strategies, including standard and targeted biologic immunosuppressants, many patients with LN fail to achieve long-term remission, leaving a significant need for safer and more effective therapies. In recent years, T-cell-based therapies have emerged as a promising frontier in the treatment of a variety of conditions including autoimmune diseases. Specifically, chimeric antigen receptor (CAR) T-cell therapies aimed at depleting antibody-producing B cells have demonstrated the ability to restore immune tolerance in several preclinical models of diseases with B-cell-driven pathologies, including SLE. In the case of LN, CAR T-cell therapies have also been deployed in clinical trials to treat patients with refractory disease. The positive results of initial clinical trials provide strong evidence that B-cell-targeted cellular therapies such as CAR T cells targeting B-cell markers CD19 and B-cell maturation antigen (BCMA) might be an effective modality for rebalancing the immune system through the elimination of autoreactive B cells. This review examines the current state of CAR T-cell therapies and their applications in LN by exploring the mechanisms, challenges, and the potential of this unique treatment approach.

This study compared the efficacy and safety of the modified BEAM (mitoxantrone hydrochloride liposome replacing melphalan) versus BEAM/BEAC as a conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with non-Hodgkin lymphoma (NHL). The data source for the modified BEAM regimen was obtained from a prospective, single-arm study (NCT05681403), while the BEAM/BEAC regimen was retrospectively collected from an electronic health record-derived external control group. Primary endpoint was the cumulative incidence of relapse (CIR). Eighty-three patients were included, with 34 in the modified BEAM group, 23 in the BEAM group, and 26 in the BEAC group. The median times were 10.5, 9.0, and 9.0 days for neutrophil engraftment, and 10.5, 10.0, and 10.0 days for platelet engraftment, respectively. Oral mucositis (14.7%, 21.7%, and 7.7%), nausea (8.8%, 17.4%, and 0.0%), and diarrhea (5.9%, 8.2%, and 0.0%) were the most common grade 3-4 non-hematologic toxicities in three groups. No treatment-related death was reported. Besides, no significant differences were observed in 2-year CIR (9.4%, 26.6%, and 23.6%), progression-free survival (90.6%, 73.4%, and 76.4%), and overall survival (97.1%, 87.0%, and 88.5%) rates among three groups (all P > 0.05). The modified BEAM conditioning regimen may have comparable efficacy and safety with the BEAM/BEAC regimen in treating patients with NHL.

Stroke, a neurological condition from compromised cerebral blood perfusion, remains a major global cause of mortality and disability. Conventional therapies like tissue plasminogen activator are limited by narrow therapeutic windows and potential adverse effects, highlighting the urgency for novel treatments. Stem cell-based therapies, with their neuroprotective and regenerative properties, present a promising yet highly diverse alternative. By conducting literature search and data extraction from the PubMed, Embase, and Cochrane databases, this meta-analysis assessed the clinical efficacy and safety of stem cell-based therapies administered via intravenous (IV) and non-IV routes in 17 studies with stroke patients. Primary outcomes included the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS), while secondary outcomes included mortality and adverse events. Results demonstrated significant improvements in NIHSS, BI, and mRS scores, particularly in non-IV groups within 6- and 12-month follow-ups, suggesting delayed but enhanced therapeutic efficacy. Mortality was reduced in both IV and non-IV groups, indicating treatment safety. Adverse events, categorized into neurological and systemic complications, showed no significant differences between intervention and control groups, further emphasizing the safety of stem cell therapies. Non-IV routes showed more long-term benefits, potentially due to enhanced cell delivery and integration. These findings demonstrate the potential of stem cell therapies to improve functional recovery and survival in stroke patients, regardless of administration route. However, the delayed response underscores the need for extended follow-up in clinical applications. Further research is required to standardize treatment protocols, optimize cell types and doses, and address patient-specific factors to integrate stem cell therapies into routine clinical practice.

Mesenchymal stromal cells (MSCs) possess therapeutic properties, which can be blunted by obesity. Autophagy, a cellular recycling process, is essential for MSC function. We investigated the mechanisms by which obesity affects the properties of MSCs, with a focus on autophagy. Adipose tissue was obtained from kidney donors [body mass index (BMI) <30 kg/m², non-obese] or individuals undergoing weight loss surgery (BMI ≥30 kg/m², obese) for MSC harvesting (n = 11 each); samples were randomized to sequencing (seq; n = 5 each) or functional studies (n = 6 each). MSCs were sequenced to determine their epigenetic (5-hydroxymethylcytosine) and transcriptomic profiles across autophagy-related genes using hydroxymethylated DNA immunoprecipitation sequencing and mRNA-seq, respectively. Genes with shared trends in both datasets underwent Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) validation. During functional studies, 2-h starvation was used to induce autophagy in vitro, enabling detection of changes in the protein expression of microtubule-associated protein 1A/1B-light chain-3 and in autophagic flux. Obesity amplified a starvation-induced reduction in autophagic flux in MSCs while promoting earlier generation of new autophagosomes during autophagy initiation. Integrated analysis of the two sequencing datasets revealed 124 differentially hydroxymethylated genes and 30 differentially expressed mRNAs. Among six overlapping autophagy-related genes, three exhibited same-direction trends. Of these, STX12 and SLC25A4 may be implicated in the impact of obesity on autophagic changes in MSCs. Therefore, human obesity may alter autophagy in adipose tissue-derived MSC, and thereby their metabolism and function.

We previously found that intravenous injection of extracellular vesicles (EVs) from human adipose tissue-derived stem cells (hADSC) could ameliorate allergic rhinitis (AR) in mice through immunomodulatory effects. In clinical trials, nasal delivery has been an attractive treatment for AR. We sought to determine whether there are differences in the therapeutic effects between caudal injection and their combination. We treated AR mice with ADSC-EVs via caudal vein, nasal cavity, or both. After treatment, the mice were re-sensitized and the indices of behavior, nasal mucosa morphology, and cytokine secretion of the mice under different modes of administration were calculated. The resultes show that tail vein, nasal, and combined administration could effectively relieve the inflammatory infiltration of the nasal mucosa of mice, reduce the secretion of IgE, IL-4, and other inflammatory factors, and alleviate the Th1/Th2 imbalance. Injection and nasal delivery, as well as their combination, effectively alleviated the symptoms of rhinitis in mice. Nasal administration has a better therapeutic effect when the inflammatory response is mild. It could be speculated that ADSC-EVs have excellent properties in the treatment of AR, and modes of administration can be selected for different stages of treatment in clinical therapy.

This study aimed to investigate the impact of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) on food allergy (FA) mice induced by ovalbumin. The percentage of regulatory T cells (Tregs) was assessed by administering hUC-MSCs intravenously to FA mouse models with oral challenges, allergic responses and levels of related allergic cytokines. The phenotypes of hUC-MSCs were analysed using flow cytometric analysis. Immunohistochemistry was used for histology observation. Real-time polymerase chain reaction (PCR) was used for gene expression. Jejunum tissue was analysed by transcriptome sequencing. Our results demonstrated that in the current FA model, hUC-MSC therapy significantly alleviated allergic responses and diarrhoea. Levels of immunoglobulin E (IgE), as well as cytokines, such as interleukin (IL)-6 and tumour necrosis factor-α associated with T helper 2 cells, were reduced. Conversely, transforming growth factor (TGF)-β levels increased with hUC-MSC therapy. In addition, enhanced TGF-β expression along with IL-10 messenger ribonucleic acid levels and an increased percentage of CD4⁺Foxp3⁺ Tregs were observed. In long-term FA mice models, hUC-MSC therapy exhibited sustained effects in mitigating rectal temperature decrease and mortality rates while reducing the levels of IgE, IL-6 and proportion of IgE+ cells; it also elevated TGF-β levels. Furthermore, hUC-MSC therapy attenuated pathological injury in both current and long-term FA mouse models. Transcriptome sequencing showed that upregulated differentially expressed genes were mainly concentrated in neural activation-ligand interaction, the cyclic guanosine monophosphate-protein kinase G signalling pathway and the TGF-β signalling pathway. The hUC-MSC therapy holds promise for alleviating both immediate and persistent FA conditions; targeting TGF-β and IL-10 secreted by hUC-MSCs may be a potential approach for treating FA.

Leucine-rich repeat-containing G-protein-coupled receptors regulate stem cell activity and tissue homeostasis within female reproductive organs, primarily through their interaction with the Wnt/β-catenin signaling pathway. LGR4-6 are increasingly recognized for their roles in organ development, regeneration, and cancer. This review aims to provide a comprehensive overview of the roles of LGR4-6 in female reproductive organs, highlighting their significance in normal physiology and disease states, specifically in the context of ovarian cancer. LGR4 is essential for the proper development of the female reproductive system; its deficiency leads to significant reproductive abnormalities, including delayed menarche and follicle development issues. LGR5 is a well-established marker of stem cells in the ovary and fallopian tubes. It has been implicated in the pathogenesis of high-grade serous ovarian cancer. LGR6, while less studied, shares functional similarities with LGR5 and can maintain stemness. It contributes to chemoresistance in ovarian cancer. LGR6 is a marker for fallopian tube stem cells and is involved in stem cell maintenance and differentiation. LGR4-6 regulate the pathophysiology of female reproductive tissues. LGR4-6 are promising therapeutic targets for treating reproductive cancers and other related disorders. Molecular mechanisms underlying the functions of LGR4-6 should be studied.

The lung is a vital organ in the respiratory system, and there is a critical need to develop more effective methods for lung health management. Extracellular vesicles (EVs) play an important role in intercellular communication. They exhibit high bioavailability and low immunogenicity, making them essential in maintaining cellular homeostasis and in the prevention and treatment of numerous diseases. This review describes the diverse sources, isolation techniques, functions, and challenges associated with EVs, particularly exosomes. We highlight their significant role in the diagnosis and treatment of lung diseases, as well as their potential as drug delivery vehicles. By synthesizing recent advances in EVs research, this review aims to provide a theoretical foundation for future studies and clinical applications of EVs.

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine from the urethra due to increased abdominal pressure. The complex pathophysiological mechanisms underlying SUI have driven the development of diverse therapeutic strategies. Current treatment options encompass both conservative and surgical interventions, with surgical approaches generally often regarded as the most effective option approach for severe cases. However, many surgical techniques carry significant risks of complications. In this context, urethral injection therapy, primarily based on stem cell-mediated regenerative approaches, has emerged as a minimally invasive alternative. Stem cell therapies leverage their multipotent differentiation capacity and paracrine signaling pathways to directly target the pathophysiological contributors to SUI, including urethral sphincter dysfunction, neuromuscular junction degeneration, and imbalances in elastin and collagen homeostasis. This narrative review provides a critical evaluation of current stem cell-mediated regenerative strategies for SUI, focusing on cellular mechanisms and the therapeutic effects driven by paracrine signaling. Recent clinical advances, unresolved scientific controversies, and innovative combinatorial delivery systems incorporating targeted therapeutic approaches are analyzed. Despite challenges remain, such as determining the optimal stem cell dosage and improving in vivo survival rates, ongoing research offers valuable insights into the development of cell-free bioactive derivatives, advanced combination delivery systems, and precise molecularly targeted therapies.

This study presents an examination of whether the double overexpression of ZNF746 and cellular prion protein (PrP^C) genes in rat adipose-derived mesenchymal stromal cells (ADMSCs) (ie, MSC^DGe-OVE) offered enhanced protection to the livers of rats against ischemia‒reperfusion (IR) injury. The in vitro results revealed that compared with those of rat ADMSCs, cell activities (viability/proliferation/growth/cell cycle process) were significantly upregulated by the overexpression of either gene in rat ADMSCs and were further significantly increased by MSC^DGe-OVE, whereas the expression of biomarkers of oxidative stress/ROS/apoptosis/fibrosis/autophagy decreased with increasing cell viability among the groups (all P < 0.001). Male adult SD rats (n = 50) were equally categorized into groups 1 (sham-operated-control), 2 (IR), 3 (IR-MSC^OVE-PrPC), 4 (IR-MSC^{OVE- ZNF746}), and 5 (IR-MSC^DGe-OVE), and livers were harvested by day 3. By day 3, the number of circulatory inflammatory/immune cells, protein expression of oxidative stress/apoptotic/fibrotic/mitochondrial damage/autophagic biomarkers, and cellular levels of DNA damage/fibrosis/inflammation in the liver parenchyma were lowest in group 1, highest in group 2 and significantly lower in groups 3/4 than in group 5 (all P < 0.0001). Liver fibrosis detected by ultrasound and the liver injury score displayed identical patterns of circulatory levels of immune cells among the groups (all P < 0.0001). Upstream and downstream inflammatory and cell-stress signaling pathways were identified as playing crucial roles in acute liver IR injury. In conclusion, MSC^DGe-OVE enhanced cell proliferation and growth and ameliorated IR-induced liver damage.