Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04921-w
Background Lung ischemia–reperfusion injury (IRI) is a major contributor to primary graft dysfunction (PGD) after lung transplantation. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising therapeutic agents in inflammatory diseases by ameliorating tissue damage and promoting repair. However, the anti-inflammatory efficacy of these approaches and the underlying mechanisms in lung ischemia–reperfusion injury remain incompletely understood. Methods The protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) against lung ischemia–reperfusion injury were evaluated using two delivery approaches, inhalation and intravenous injection. Both in vivo and in vitro models were employed to assess the biological activity of MSC-EVs and to elucidate the underlying molecular mechanisms. In addition, a rat orthotopic lung transplantation (OLT) model was established to further examine the translational relevance of MSC-EVs. Results MSC–EVs treatment significantly ameliorated lung IRI, with inhalation showing superior efficacy over intravenous delivery. Mechanistically, miR-22-3p within MSC-EVs targeted macrophage NLRP3, suppressing activation of the NLRP3/Caspase-1/IL-1β pathway and promoting M2 polarization. The protective efficacy was confirmed in a clinically relevant rat OLT model, underscoring their translational potential
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04401-7
Background: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitive therapeutic schedule for the disease. Bone marrow mesenchymal stem cells (BMSCs), exhibiting neuroimmune-modulatory functions to alleviate various autoimmune diseases, show great potential in the treatment of MS. However, the instability of BMSCs-mediated immunosuppression in vivo has limited their application. MiR181-a, a positive regulator of immune balance, which has a preference for T cells and B cells differentiation, but degrade rapidly upon entering systemic circulation due to their unstable molecular structure. Methods: We propose a synergistic therapy approach that combines the penetrative targeting capability of BMSCs with the immuno-modulatory effects of miR181-a by overexpressing miR181-a to BMSCs through lentivirus packaging system. With this strategy, on the basis of the establishment of the experimental autoimmune encephalomyelitis (EAE) model, miR181-a overexpressing BMSCs (miR181a-BMSCs) would have a stronger immuno-modulatory treatment benefit, in terms of attenuating MS development. Results: Indicate that this method prolongs the modulatory effects of BMSCs and resulted in significantly enhancements of the proliferation of regulatory B cells (Bregs), regulatory T cells (Tregs) and the inhibition of Th17 cells compared to the traditional BMSCs group. Moreover, 10-fold miRNA’s concentration in the exosome of miR181a-BMSCs, leading to an increased duration of miRNAs to exert their biological effects. By immunotherapy and synergistic treatment, the effectiveness of the treatment is significantly enhanced, showing consistent results in different groups of the animal model.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04788-3
End-stage liver disease (ESLD) is one of the predominant diseases contributing to high morbidity and mortality worldwide, with etiologies including alcoholic liver disease, viral hepatitis, non-alcoholic fatty liver disease, and metabolic-associated liver disease. Currently, liver transplantation remains the only effective treatment, however, its clinical application is significantly limited by donor shortages, immune rejection, and high medical costs. Among the five types of stem cells that have been experimentally applied to liver diseases, mesenchymal stem cells (MSCs) have emerged as the most extensively studied, with the largest number of experimental and clinical research platforms worldwide. This review compiles findings from 25 preclinical and clinical studies on MSCs in the treatment of ESLD, aiming to elucidate the core mechanisms of action and then outline both the challenges in MSC clinical translation and the novel opportunities arising from cutting-edge research.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03945-4
Background Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. Methods To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. Results Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. Conclusion Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025055
Platelets circulate in an inactive form in the body until they contact with defective areas of endothelial cells or encounter a clotting cascade [1]. Activated platelets release and express bioactive substances and acquire the ability to bind plasma fibrinogen. Abnormal activation of platelets is involved in atherosclerosis and thrombosis [2,3]. When platelets are stimulated and activated, phospholipase A2 is activated at the same time, which then cleaves membrane phospholipids and frees arachidonic acid (AA) [4]. The latter catalyzes thromboxane A2 (TXA2) via thromboxane synthetase [5], which is induced by the cyclooxygenase COX-1 to produce prostaglandins G2 and H2 [6]. TXA2 is highly unstable, with a half-life of only 30 s, and it is rapidly hydrolyzed to relatively stable thromboxane B2 (TXB2), which is then converted in the liver to 11-dehydrothromboxane B2 (11dH-TXB2), which has a longer half-life and is excreted in the urine [7]. Dehydrothromboxane B2 is the final stable metabolite of thromboxane A2, which is derived only from arachidonic acid metabolism and can represent thromboxane A2 level in the body [8]. Specifically, by inhibiting the action of COX-1, the most important enzyme in the process of arachidonic acid metabolism, aspirin inhibits the production of thromboxane A2, that is, the concentration of TXA2 affects the effect of aspirin on platelet aggregation. However, the half-life of TXA2 (including the metabolic intermediate TXB2) is too short to be accurately measured, so the detection of its metabolic end product 11dH-TXB2 can very accurately reflect the sensitivity of the body to aspirin [7]. The concentration of 11dH-TXB2 in the serum correlates well with the concentration of 11dH-TXB2 in the urine, so the determination of 11dH-TXB2 in the urine can more effectively reflect the production of TXA2 in vivo [8]. The 11dH-TXB2 concentration needs to be corrected with the urinary creatinine concentration to rule out the effects of the urine concentration and renal function, so random urine samples can be used for testing [6]. Aspirin can acetylate serine at the key site of cyclooxygenase and thus irreversibly inhibits the activity of COX-1, reduces the synthesis of TXA2, and blocks the production of TXA2 and its induced platelet aggregation. Low-dose aspirin (30–75 mg/day) can effectively inhibit 95% of COX-1 activity [7]. Since the production of TXA2 in serum is largely dependent on platelet COX-1 (a therapeutic target of aspirin), 11dH-TXB2 can be used as a monitor for aspirin-induced platelet inhibition [3]. Creatinine is a metabolic byproduct of muscle metabolism that is primarily excreted via glomerular filtration, and its level is indicative of renal function [9]. The 24-h creatinine clearance can also be used to determine the integrity of the sample or to correct the urine sample concentration with the creatinine ratio [10]. Currently, creatinine detection methods include the Jaffe method, enzymolysis spectrophotometry, HPLC, capillary electrophoresis, capillary zone electrophoresis, gas chromatography tandem mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) [11]. At present, there is no method for the simultaneous detection of 11dH-TXB2 and creatinine. When both analytes are needed, separate tests must be performed, increasing the workload and sample volume requirements. Thus, developing a method that enables the concurrent quantification of 11dH-TXB2 and creatinine in a single assay remains a critical challenge. The aim of this study was to provide a method for the simultaneous detection of 11dH-TXB2 and creatinine and to alleviate the problem that 11dH-TXB2 and creatinine cannot be simultaneously detected. By developing a standardized quantitative approach for measuring 11dHTXB2 and creatinine in human urine, this study aims to provide reliable concentration data, thereby facilitating further clinical research and methodology optimization.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023264
Cellular senescence is an important factor leading to pulmonary fibrosis. Deficiency of 8-oxoguanine DNA glycosylase (OGG1) in mice leads to alleviation of bleomycin (BLM)-induced mouse pulmonary fibrosis, and inhibition of the OGG1 enzyme reduces the epithelial mesenchymal transition (EMT) in lung cells. In the present study, we find decreased expression of OGG1 in aged mice and BLM-induced cell senescence. In addition, a decrease in OGG1 expression results in cell senescence, such as increases in the percentage of SA-β-gal-positive cells, and in the p21 and p-H2AX protein levels in response to BLM in lung cells. Furthermore, OGG1 promotes cell transformation in A549 cells in the presence of BLM. We also find that OGG1 siRNA impedes cell cycle progression and inhibits the levels of telomerase reverse transcriptase (TERT) and LaminB1 in BLM-treated lung cells. The increase in OGG1 expression results in the opposite phenomenon. The mRNA levels of senescence-associated secretory phenotype (SASP) components, including IL-1α, IL-1β, IL-6, IL-8, CXCL1/CXCL2, and MMP-3, in the absence of OGG1 are obviously increased in A549 cells treated with BLM. Interestingly, we demonstrate that OGG1 binds to p53 to inhibit the activation of p53 and that silencing of p53 reverses the inhibition of OGG1 on senescence in lung cells. Additionally, the augmented cell senescence is shown in vivo in OGG1-deficient mice. Overall, we provide direct evidence in vivo and in vitro that OGG1 plays an important role in protecting tissue cells against aging associated with the p53 pathway.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04921-w
Lung ischemia-reperfusion injury (IRI) remains the principal driver of primary graft dysfunction (PGD) following transplantation, with no approved pharmacological prophylaxis. This study evaluated mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) delivered by inhalation versus intravenous injection in murine hilar clamp and rat orthotopic lung transplantation (OLT) models. Inhalation achieved superior attenuation of pulmonary injury relative to systemic administration. Mechanistically, MSC-EV-encapsulated miR-22-3p was delivered to alveolar macrophages, where it targeted NLRP3 and suppressed the ASC/Caspase-1/IL-1β axis, reducing pyroptosis and promoting M2 polarization. These effects lowered cytokine-driven damage and enhanced tissue repair. Efficacy was confirmed in a clinically relevant rat OLT model, supporting translational potential for PGD prevention. The findings establish a pathway-specific, cell-free therapeutic strategy with a favorable route-dependent efficacy profile.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21562
BACKGROUND: Previous studies have confirmed that the Bushen Jianpi Huoxue Formula can increase bone mineral density in osteoporotic rats. OBJECTIVE: To investigate the effect of Bushen Jianpi Huoxue Formula on bone loss and trabecular biomechanical parameters in ovariectomized rats. METHODS: Fifty female Sprague-Dawley rats were randomly divided into five groups: normal group (n=10) without any intervention, sham-operated group (n=10) with removal of adipose tissue near the ovaries, ovariectomized group (n=10), Bushen Jianpi Huoxue Formula group (n=10), and alendronate group (n=10). The latter three groups underwent bilateral ovariectomy to establish osteoporosis models. After 12 weeks of modeling, the Bushen Jianpi Huoxue Formula group and alendronate group were administered the respective drugs by gavage once daily for 12 weeks, while the other three groups received normal saline. After treatment, lumbar spine bone mineral density was measured, micro-CT analysis of the distal femur and proximal tibia was performed, hematoxylin-eosin staining was used to observe the histological morphology of the proximal tibia, and finite element analysis was used to analyze the strain and stress of the distal femur. RESULTS AND CONCLUSION: (1) The lumbar spine bone mineral density in the ovariectomized group was lower than that in the normal and sham-operated groups (P < 0.05), while the Bushen Jianpi Huoxue Formula and alendronate groups had higher lumbar spine bone mineral density than the ovariectomized group (P < 0.05). (2) Micro-CT analysis showed that compared with the normal and sham-operated groups, the ovariectomized group had lower bone volume fraction, bone surface density, and trabecular number in the proximal tibia (or distal femur) (P < 0.05), and higher trabecular separation and structure model index (P < 0.05). Compared with the ovariectomized group, the Bushen Jianpi Huoxue Formula and alendronate groups had higher bone volume fraction, bone surface density, and trabecular number in the distal femur (P < 0.05), and lower trabecular separation and structure model index in the distal femur (P < 0.05); in the proximal tibia, bone volume fraction, bone surface density, and trabecular number were also higher (P < 0.05). (3) Hematoxylin-eosin staining showed that the degree of bone marrow fat infiltration in the ovariectomized group was higher than that in the normal and sham-operated groups, while the Bushen Jianpi Huoxue Formula and alendronate groups showed significant improvement. (4) Finite element analysis showed that under the same load, the trabecular stress and strain in the ovariectomized group were higher than those in the normal and sham-operated groups (P < 0.05), while the Bushen Jianpi Huoxue Formula and alendronate groups had lower trabecular stress and strain than the ovariectomized group (P < 0.05). These results indicate that Bushen Jianpi Huoxue Formula can prevent bone loss and improve trabecular biomechanical properties in ovariectomized rats, suggesting potential efficacy in preventing osteoporotic fractures.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025055
Thromboxane A2 (TXA2) is a labile eicosanoid with a half-life of 30 s, limiting direct quantification. Its stable urinary metabolite, 11-dehydrothromboxane B2 (11dH-TXB2), reflects in vivo TXA2 biosynthesis and aspirin-mediated COX-1 inhibition. Creatinine normalization is required to correct for urine concentration and renal function. This study establishes a quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of 11dH-TXB2 and creatinine in human urine. Sample pretreatment involves organic phase extraction, eliminating solid-phase extraction. The method was validated for linearity, accuracy, precision, and recovery. The linear range for 11dH-TXB2 was 0.1–50 ng/mL (r² = 0.99656) and for creatinine 10–5000 ng/mL (r² = 0.99950). Quality control accuracies ranged from 85.83% to 113.21%, with RSDs below 9.71%. Standard recoveries were 85–110%. The assay meets regulatory requirements for simultaneous quantification. This approach provides a reliable tool for monitoring aspirin response and investigating thromboxane-related pathologies.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781714596256
Background: The inflammatory burden index (IBI), derived from C-reactive protein (CRP) and albumin, has emerged as a prognostic biomarker in various cancers. However, its role in non-small cell lung cancer (NSCLC) remains unclear. Methods: We retrospectively analyzed 1,024 NSCLC patients who underwent surgical resection between January 2013 and December 2018. The IBI was calculated as CRP × albumin. Optimal cutoff values were determined by X-tile software. Patients were divided into high and low IBI groups. Univariate and multivariate Cox regression analyses identified independent prognostic factors. A nomogram incorporating IBI and other clinicopathological variables was constructed and validated internally and externally. Model performance was assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: The optimal cutoff for IBI was 0.36. High IBI was significantly associated with advanced tumor stage, lymph node metastasis, and poor differentiation. Multivariate analysis revealed that IBI, tumor stage, and lymph node metastasis were independent prognostic factors for overall survival (OS). The nomogram achieved a C-index of 0.72 (95% CI: 0.68-0.76) in the training cohort and 0.70 (95% CI: 0.65-0.75) in the validation cohort. Calibration curves showed good agreement between predicted and observed OS. DCA demonstrated that the nomogram provided a net clinical benefit. Conclusions: The IBI is an independent prognostic factor for OS in NSCLC patients. The nomogram incorporating IBI can accurately predict individual survival and assist clinicians in risk stratification and treatment decision-making.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731785313317742
Background: Heart failure with recovered ejection fraction (HFrecEF) is a distinct phenotype with unclear clinical characteristics and prognosis. Methods: We prospectively enrolled 1,234 patients with heart failure and reduced ejection fraction (HFrEF) from January 2015 to December 2018. After optimal medical therapy, 312 patients (25.3%) achieved recovery of left ventricular ejection fraction (LVEF) to ≥50% and were classified as HFrecEF. Clinical characteristics, medication use, and outcomes were compared with those who remained HFrEF. The primary outcome was a composite of all-cause death and heart failure hospitalization. Results: Compared with HFrEF patients, HFrecEF patients were younger, more likely to be female, had a higher prevalence of hypertension and atrial fibrillation, and had a shorter duration of heart failure. They had lower baseline levels of NT-proBNP and smaller left ventricular dimensions. Over a median follow-up of 3.2 years, HFrecEF patients had a significantly lower risk of the primary outcome (adjusted HR 0.45, 95% CI 0.32-0.63, p<0.001). However, 23.4% of HFrecEF patients experienced deterioration of LVEF during follow-up, and these patients had a worse prognosis compared with those who maintained recovery. Independent predictors of LVEF deterioration included ischemic etiology, diabetes, and non-adherence to guideline-directed medical therapy. Conclusions: HFrecEF is associated with a better prognosis than HFrEF, but a substantial proportion of patients may experience LVEF deterioration. Continued optimization of medical therapy and close monitoring are essential for this population.