Qin Liu

Background The limited proliferative lifespan and progressive senescence of primary mesenchymal stromal cells (MSCs) restrict their long-term expansion and experimental reproducibility. Establishing immortalized MSC lines with preserved biological properties may provide a useful cell resource for basic and preclinical studies. Methods Rat bone marrow-derived MSCs (rBMSCs) were transduced with human telomerase reverse transcriptase (hTERT). The resulting cells were characterized by morphology, hTERT expression, telomerase activity, proliferation, senescence-associated changes, immunophenotype, multilineage differentiation, paracrine-related assays, and tumorigenicity-related assays. Their in vivo activity was further evaluated in an acute dextran sulfate sodium (DSS)-induced colitis model in mice. Results hTERT-rBMSCs maintained a fibroblast-like morphology during long-term culture and showed stable hTERT expression with increased telomerase activity. Compared with late-passage primary rBMSCs, hTERT-rBMSCs exhibited enhanced proliferative capacity, reduced senescence-associated β-galactosidase staining, and lower expression of senescence-related genes. The immortalized cells retained typical MSC surface marker expression and multilineage differentiation potential. Under the tested experimental conditions, hTERT-rBMSCs did not exhibit detectable anchorage-independent growth in soft agar or tumor formation in nude mice. In the DSS-induced colitis model, hTERT-rBMSCs alleviated body weight loss, reduced disease activity, improved colon length and histological appearance, and decreased colonic inflammatory cytokine expression. Their therapeutic effects were broadly comparable to those of primary rBMSCs. Conclusions hTERT-mediated immortalization generated a rat BMSC population with extended proliferative capacity, delayed senescence, and preserved phenotypic and functional characteristics. Under the present experimental conditions, hTERT-rBMSCs retained anti-colitis activity in vivo and may serve as a useful cell resource for studies requiring stable and expandable MSCs.

Systemic factors found in young blood possess the capacity to revitalize the aging brain, yet the clinical translation of human-derived therapeutics is sev

Background: Vibrio harveyi is a major bacterial pathogen threatening turbot aquaculture, necessitating the development of more effective vaccines. Bacterial ghosts (BGs), which are empty bacterial envelopes with preserved surface antigens, offer a promising alternative to traditional formaldehyde-killed vaccines that often suffer from reduced immunogenicity. Methods: We developed an optimized BGs vaccine for V. harveyi by combining the nonionic surfactant NP-40 with sodium hydroxide (NaOH). This NP-40/NaOH combination demonstrated a synergistic lytic effect, halving the minimum inhibitory concentration of NaOH required for complete inactivation. Results: The resulting BGs exhibited intact cellular morphology with transmembrane pores, efficient removal of cytoplasmic contents, and significantly better preservation of lipopolysaccharide structure compared to NaOH-alone treatment. Vaccination trials in turbot demonstrated that the NP-40/NaOH BGs provided the highest relative percent survival (RPS = 58.8%) upon challenge, outperforming both NaOH-alone BGs (RPS = 55.0%) and a traditional formaldehyde-killed vaccine (RPS = 34.8%). The superior protection was correlated with the induction of a more robust and sustained immune response, characterized by significantly higher levels of specific IgM antibodies, elevated lysozyme activity, and increased total serum protein. Conclusions: This study establishes the NP-40/NaOH protocol as an effective strategy for producing high-quality BGs with enhanced immunogenicity, presenting a potent vaccine candidate for controlling vibriosis in aquaculture.

MRNA vaccines have demonstrated significant potential in preventing human diseases and controlling livestock infections. However, the application of mRNA vaccines in aquaculture, especially on fish, remains limited. Infectious hematopoietic necrosis virus (IHNV) is an RNA virus that mainly affects rainbow trout (Oncorhynchus mykiss), leading to high mortality rates. In this study, we systematically engineered three UTR-optimized mRNA constructs, exhibiting comparable and sustained in vitro antigen expression. Following encapsulation, the mG1-LNP formulation, incorporating endogenous antigen-specifics, conferred robust relative protection against IHNV challenge, accompanied by enhanced levels of IgM and neutralizing antibodies. Furthermore, dose-response profiling identified 10 μg/dose as the immunologically optimized regimen, eliciting efficient immunogenicity. Moreover, biodistribution analyses revealed complete mG1-LNP clearance from injection sites and hepatic tissues by 28 dpv, confirming favorable biosafety. Collectively, our work demonstrates the successful development of mRNA-LNP vaccine against infectious IHNV in rainbow trout, providing the first empirical demonstration of mRNA-LNP vaccine efficacy in aquaculture.

The treatment of inflammatory bowel disease (IBD) urgently requires effective and safe strategies, and mesenchymal stem cell (MSC)-based therapy has emerged as a research focus due to its immunomodulatory and tissue-repairing capabilities. To enhance the therapeutic efficacy of MSCs, this study developed a decellularized small intestinal (dSI) hydrogel delivery system to encapsulate rat bone marrow-derived MSCs (rBMSCs) for targeted rectal administration to colitis lesions in mice. Results demonstrated that the dSI hydrogel significantly improved the in vivo survival rate of rBMSCs and effectively alleviated dextran sulfate sodium (DSS)-induced colitis symptoms. The dSI hydrogel significantly improved rBMSCs survival in vivo and ameliorated DSS-induced colitis by: suppression of pro-inflammatory cytokines and myeloperoxidase (MPO) expression; restoration of intestinal barrier function and promotion of mucosal regeneration. The dSI hydrogel outperformed conventional PLGA-PEG-PLGA hydrogels in tissue repair due to its superior bioactivity, biocompatibility, biodegradability, and mechanical properties, while its low immunogenicity ensured therapeutic safety. The combined treatment mitigated inflammation, oxidative stress, and tissue damage through multi-target synergistic effects, offering a novel therapeutic approach for IBD. Future studies should further investigate the interaction mechanisms between dSI hydrogel and rBMSCs, optimize dosing regimens, and employ single-cell RNA sequencing to elucidate MSC-mediated immunomodulation in the gut microenvironment. This study provides experimental evidence for the clinical translation of dSI hydrogel-based MSC therapy, highlighting its potential as a promising strategy for IBD treatment.