Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Background Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Methods Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Results Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04148-1
Background The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. Methods One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n=65, 4×10^7 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. Results Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR]=1.68, 95% confidence interval [CI]: 0.65–4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44–24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China’s dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR=0.54, 95% CI: 0.20–1.41). Conclusions These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms. Trial registration: ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03984-x
This correction article addresses an inadvertent error in the original publication. In Fig. 5M of the original article, the image of the fourth lane (LEF-1) of the second picture (Doxorubicin-induced GCSCs) was inadvertently replaced with an incorrect version during the upload process. The authors wish to note a correction to the aforementioned picture via the corrected picture ahead in this Correction article. The authors deeply regret that this error occurred and sincerely apologize for any inconvenience.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025091
One of the characteristics of malignant tumors is heterogeneity, which refers to the molecular or genetic differences among progeny cells during tumor growth. This heterogeneity contributes to variations in the tumor growth rate, invasive ability, drug sensitivity, and prognosis. To gain a deeper understanding of the molecular background underlying tumor heterogeneity, we construct monoclonal cell lines derived from the glioblastoma (GBM) cell line U87-MG by limiting dilution assays. The selected CF5 and G11 subclones exhibit completely different cell morphologies and, more importantly, distinct functional phenotypes. CF5 exhibits stronger proliferative properties and chemoresistance, whereas G11 shows greater motility and invasion. Transcriptomic sequencing reveals great differences in gene expression among the CF5, G11, and U87 cell lines, and downregulated genes in individual clones are significantly enriched in gene sets related to extracellular matrix function. ITGA11 and ITGA6, as research subjects, are demonstrated to exclusively regulate functional phenotypes and chemotherapy sensitivity in CF5 or G11 cells. In U87 cells, combined knockdown of these two genes significantly inhibits tumor growth and increases chemotherapy sensitivity, but knockdown of either gene alone does not. In summary, these data reveal that even under uniform growth conditions, the heterogeneity of tumor cells and their diverse genetic backgrounds remain significant and persistent. This finding is crucial for accurately identifying tumor-related genes and their functional phenotypes, and a thorough understanding of the genetic and molecular background underlying tumor heterogeneity is essential for comprehensive cancer treatment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025169
AXL, a member of the TAM (Tyro3, AXL, and Mertk) subfamily of RTKs, is abundantly expressed in lung tissue and has been implicated in viral infections and lung injury. PROS1, one of the ligands known to activate AXL, functions as an immunomodulator in many diseases. However, the role of PROS1/AXL signaling in influenza A virus (IAV) infection and infection-induced lung injury is largely unknown. In this study, we find that the exogenous administration of PROS1 mitigates lung injury and protects mice from lethal infection by IAVs through the activation of AXL. PROS1 induces the phosphorylation of AXL, which in turn recruits Gab1 and p85, a regulatory subunit of PI3K, to form a complex that activates Gab1 and its downstream PI3K/AKT/mTOR in alveolar macrophages. Gab1 knockdown in vivo, or LY294002 (a PI3K inhibitor), abolishes the PROS1/AXL-induced protective activity against lethal influenza infection in mice. We also show that PROS1/AXL signaling induces M2 polarization of alveolar macrophages through Gab1 activation both in vitro and in vivo. Gab1 knockdown inhibits M2 macrophage accumulation in IAV-infected lungs and attenuates the protective effect of PROS1. These results indicate that PROS1/AXL signaling can activate Gab1 in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype, thereby eliciting protective activity against lethal infection with IAVs. These data also highlight the PROS1/AXL signal as a novel therapeutic target for IAV infection.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, driven by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration. These effects are closely associated with the activation of SIRT1/FOXO3 signaling and the restoration of functional mitophagic flux. Our work highlights the SIRT1/FOXO3-mitophagy axis as a promising target for further investigation in the development of therapeutic strategies for IVDD.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21264
BACKGROUND: Previous studies have established a correlation between non-alcoholic fatty liver disease and sarcopenia; however, their causal relationship remains uncertain. The gut-muscle-liver axis hypothesis posits intricate interactions between the gut microbiota and both sarcopenia and non-alcoholic fatty liver disease, yet the precise pathogenic mechanisms underlying these interactions remain poorly elucidated. OBJECTIVE: To investigate the potential causal relationship between sarcopenia and non-alcoholic fatty liver disease using Mendelian randomization analysis and to delve into the potential role of the gut microbiota in mediating or influencing the interplay between non-alcoholic fatty liver disease and sarcopenia. METHODS: Sarcopenia data were sourced from the UK Biobank (the UK National-Level Biomedical Database, supported by the UK government and developed in 2006 in collaboration with institutions such as the University of Oxford and the University of Manchester, which encompasses multidimensional data including genes, imaging, and health records from 500 000 participants), with relevant traits including appendicular muscle mass, grip strength, and walking speed. The non-alcoholic fatty liver disease dataset was derived from a publicly accessible GWAS summary dataset compiled by Ghodsian et al., comprising aggregated statistics from GWAS cohorts including eMERGE and FinnGen, updated GWAS data of non-alcoholic fatty liver disease from the UK Biobank, and newly conducted GWAS data from the Estonian Biobank. The 211 gut microbiota data were obtained from a large-scale human gut microbiome composition study conducted by the MiBioGen consortium. Inverse variance weighting, weighted median, MR-Egger, weighted model, and simple model methods were used to assess the mutual influences among non-alcoholic fatty liver disease, sarcopenia, and gut microbiota-related traits. RESULTS AND CONCLUSION: The inverse variance weighting analysis indicated that walking speed and appendicular muscle mass were negatively correlated with non-alcoholic fatty liver disease, while left and right hand grip strength showed no significant correlation with non-alcoholic fatty liver disease risk. Reverse Mendelian randomization analysis showed that non-alcoholic fatty liver disease was negatively correlated with appendicular muscle mass, but no significant correlation was found between non-alcoholic fatty liver disease and walking speed or left and right hand grip strength. Thirty-nine gut microbiota taxa were significantly associated with sarcopenia onset, and six gut microbiota taxa had a causal relationship with non-alcoholic fatty liver disease. The study suggests that gut microbiota may regulate the 'gut-liver-muscle axis' through short-chain fatty acid metabolism, providing a new direction for cross-organ mechanism research for Chinese scholars. Combined with the unique genetic background of the Chinese population (such as ALDH2 mutations and genes related to high-salt diet), it can further analyze the race-specific pathways of metabolic-muscle comorbidity, providing a scientific basis for formulating dietary recommendations that conform to the Chinese dietary structure (such as high grain intake).
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21438
BACKGROUND: Early diagnosis and treatment of osteoarthritis remain a significant challenge due to the lack of highly specific biomarkers. OBJECTIVE: To screen characteristic genes of osteoarthritis, predict potential food-medicine homology traditional Chinese medicine and their core components, and validate their therapeutic potential through molecular docking and molecular dynamics simulations. METHODS: This study is based on three datasets (GSE55235, GSE169077, and GSE55457) from the GEO database, including a total of 25 normal samples and 26 osteoarthritis samples. It combines genes extracted from the eQTL database as exposure factors, and osteoarthritis data from the IEU openGWAS database (407,746 samples) as outcome factors. Core biomarkers were identified using least absolute shrinkage and selection operator regression, random forest, and support vector machine algorithms. CIBERSORT was used to evaluate immune infiltration characteristics and single-gene gene set enrichment analysis was performed. Potential traditional Chinese medicines were predicted using Coremine Medical and HERB databases, and food-medicine homology traditional Chinese medicines and their core components were screened, followed by molecular docking and molecular dynamics simulations. RESULTS AND CONCLUSION: ① Two genes, glucose transporter 3 (GLUT3) and atypical chemokine receptor 1 (ACKR1), were identified as characteristic genes of osteoarthritis, showing good diagnostic efficacy (AUC > 0.8) and involvement in metabolic regulation, cell signal transduction, and inflammatory responses, closely related to glucose metabolism, immune regulation, and inflammatory signaling pathways. ② Seven food-medicine homology traditional Chinese medicines were screened, including Cornus officinalis, Perilla frutescens, Ganoderma lucidum, Gastrodia elata, bitter almond, clove, and Rehmannia glutinosa, with core components β-sitosterol and stigmasterol. Molecular docking and dynamics simulations showed that stigmasterol had the best affinity with GLUT3 and the complex exhibited high stability. ③ This study systematically reveals the key roles of GLUT3 and ACKR1 in the pathogenesis of osteoarthritis, preliminarily validates the possibility of food-medicine homology traditional Chinese medicines intervening in the pathological process of osteoarthritis through multi-target and multi-pathway mechanisms, providing new molecular evidence for early diagnosis and targeted therapy, as well as theoretical support for prevention and treatment strategies. This research, from the perspective of traditional Chinese medicine and modern molecular biology, can provide a reference for the clinical application of traditional Chinese medicine in osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21452
BACKGROUND: Tendon injury repair is often compromised by inflammatory cascades and disordered collagen metabolism, leading to scar formation and mechanical deterioration. Curcumin exhibits anti-inflammatory, antioxidant, and pro-repair potential, but its rapid metabolism and low bioavailability limit clinical application. OBJECTIVE: To construct a thermosensitive injectable curcumin-loaded chitosan/sodium β-glycerophosphate hydrogel and evaluate its efficacy in tendon repair. METHODS: (1) Rat tendon stem cells were cultured with different concentrations of curcumin for 24 hours. Cell viability was assessed using the CCK-8 assay, and the 20 µmol/L concentration was selected for subsequent experiments. Rat tendon stem cells were cultured with 0 (control) and 20 µmol/L curcumin, and cell migration was assessed using a wound healing assay. Rat tendon stem cells were cultured in three groups: a control group received no treatment; a model group received tert-butyl hydroperoxide to induce oxidative stress; a curcumin group received tert-butyl hydroperoxide plus 20 µmol/L curcumin. qRT-PCR and western blot were used to detect the expression of matrix metalloproteinase 3, matrix metalloproteinase 13, collagen type I alpha 1 chain, collagen type III alpha 1 chain, Bcl-2, and Bax. (2) Chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogels with or without curcumin (final concentration 20 µmol/L) were prepared. The microstructure and drug release were characterized. Rat tendon stem cells were co-cultured with the hydrogels, and cell compatibility was evaluated by live/dead staining and cytoskeletal staining. (3) Sixty SD rats were randomly divided into five groups: sham surgery (n=12), model (n=12), hydrogel only (n=12), curcumin solution (n=12), and curcumin-loaded hydrogel (n=12). The Achilles tendon rupture model was established, and treatments were injected at the tendon stump, with a second injection after 4 days. At 8 weeks post-surgery, peritendinous adhesion, hematoxylin-eosin staining, Masson staining, immunohistochemistry for cyclooxygenase-2 and collagen type I alpha 1 chain, and biomechanical analysis were performed. RESULTS AND CONCLUSION: (1) Curcumin promoted the migration of rat tendon stem cells. Compared with the model group, the curcumin group showed decreased mRNA and protein expression of matrix metalloproteinase 3, matrix metalloproteinase 13, collagen type III alpha 1 chain, and Bax protein (P < 0.05), and increased expression of collagen type I alpha 1 chain and Bcl-2 protein (P < 0.05). (2) Scanning electron microscopy revealed a typical three-dimensional porous network structure of the hydrogel with uniform pore size and interconnected pores. The curcumin-loaded hydrogel exhibited good sustained release. Live/dead and cytoskeletal staining showed good cytocompatibility. (3) The curcumin-loaded hydrogel group had lower peritendinous adhesion than the model, hydrogel only, and curcumin solution groups. Hematoxylin-eosin and Masson staining showed reduced inflammatory cell infiltration and orderly collagen deposition in the curcumin-loaded hydrogel group. Immunohistochemistry showed lower cyclooxygenase-2 expression and higher collagen type I alpha 1 chain expression in the curcumin-loaded hydrogel group compared with the model and hydrogel only groups (P < 0.05). The maximum tensile stress and elastic modulus were higher in the curcumin-loaded hydrogel group than in the model, hydrogel only, and curcumin solution groups (P < 0.05). In conclusion, the curcumin-loaded chitosan/sodium β-glycerophosphate thermosensitive hydrogel synergistically exerts anti-inflammatory effects and promotes orderly collagen deposition, significantly improving the quality of tendon repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21451
BACKGROUND: Hydrogel materials have garnered significant attention in tissue repair due to their good biocompatibility and degradability, but single hydrogels lack antibacterial and osteogenic functions, limiting clinical application. OBJECTIVE: To prepare hydrogels with both antibacterial and osteogenic functions for bone tissue repair. METHODS: Copper and zinc co-doped hydroxyapatite (Cu/Zn HA) was synthesized by chemical precipitation. Cu/Zn HA, epigallocatechin gallate (EGCG), and Cu/Zn HA+EGCG were separately added to photoinitiators, and methacrylated gelatin (GelMA) was added to the photoinitiator solutions. After UV irradiation at 405 nm for 20 s, four hydrogels were prepared: GelMA (G), Cu/Zn HA/GelMA (G-Cu/Zn HA), EGCG-modified GelMA (G-E), and EGCG-modified Cu/Zn HA/GelMA (G-E-Cu/Zn HA). The microstructure, compressive mechanical properties, swelling, degradation, and release kinetics of metal ions and EGCG were characterized. Antibacterial properties were evaluated against Staphylococcus aureus and Escherichia coli using agar plate coating, live/dead staining, and scanning electron microscopy. Cytocompatibility was assessed with MC3T3-E1 cells via live/dead staining and CCK-8 assay. Osteogenic activity was evaluated after osteogenic induction using alkaline phosphatase staining, alizarin red S staining, and osteogenic-related gene expression. RESULTS AND CONCLUSION: Scanning electron microscopy showed porous internal structures in all hydrogels, with G and G-E having relatively smooth surfaces, while G-Cu/Zn HA and G-E-Cu/Zn HA had increased surface roughness. Compressive stresses were 10.48, 12.91, 23.64, and 41.03 kPa for G, G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA, respectively. Compared with G, the swelling time and equilibrium swelling ratio decreased in G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA. G-E-Cu/Zn HA exhibited prolonged degradation. G-Cu/Zn HA and G-E-Cu/Zn HA released Cu2+, Zn2+, and Ca2+ over 30 days, with G-Cu/Zn HA releasing more Cu2+ and Zn2+ than G-E-Cu/Zn HA. G-E-Cu/Zn HA significantly inhibited the burst release of EGCG compared with G-E. Antibacterial assays showed that all modified hydrogels inhibited bacteria, with G-E-Cu/Zn HA showing the strongest effect. All hydrogels were cytocompatible. Osteogenic assays showed that G had the weakest osteogenic ability, while G-E-Cu/Zn HA had the strongest. CONCLUSION: The EGCG-modified Cu/Zn HA/GelMA composite hydrogel exhibits excellent antibacterial and osteogenic properties.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025091
Glioblastoma multiforme (GBM) exhibits profound intratumoral heterogeneity that drives therapeutic resistance and recurrence. Using limiting dilution, we derived monoclonal sublines CF5 and G11 from the U87-MG GBM cell line. These subclones displayed divergent morphologies and functional phenotypes: CF5 demonstrated enhanced proliferation and chemoresistance, whereas G11 exhibited increased motility and invasion. Transcriptomic sequencing revealed extensive differential gene expression among CF5, G11, and parental U87 cells, with downregulated genes in individual clones significantly enriched in extracellular matrix (ECM)-related gene sets. ITGA11 and ITGA6 were identified as exclusive regulators of phenotype and chemotherapy sensitivity in CF5 and G11, respectively. In mixed U87 cells, single knockdown of either ITGA11 or ITGA6 failed to produce substantial phenotypic changes, but combined knockdown significantly inhibited tumor growth and increased chemosensitivity. These findings underscore that tumor heterogeneity and diverse genetic backgrounds persist even under uniform culture conditions, obscuring the functional contributions of individual genes in bulk populations. The study highlights the necessity of resolving subclonal expression patterns to accurately assign gene function and to design effective combinatorial targeted therapies. Subcutaneous tumor models, while not fully recapitulating the brain microenvironment, provided practical monitoring of tumor dynamics. This work challenges single-target therapeutic strategies and advocates for context-dependent molecular interventions in GBM.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025138
Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related mortality worldwide, with a five-year survival rate of approximately 15%. Despite advances in targeted therapy, the limited repertoire of actionable mutations and the inevitable emergence of drug resistance necessitate the continuous discovery of novel therapeutic agents. This study investigates the antitumor efficacy of EOAI3402143, a small-molecule inhibitor, against LUAD and elucidates its mechanism of action. Using flow cytometry, transwell, colony formation assays, western blot, RT-qPCR, and RNA-seq, we demonstrate that EOAI3402143 promotes apoptosis and suppresses migration, invasion, and proliferation of LUAD cells. Mechanistically, EOAI3402143 inhibits NF-κB pathway activation and downregulates NR4A1 expression, thereby attenuating LUAD progression. In vivo experiments confirm superior therapeutic efficacy of EOAI3402143 in LUAD models. These findings position EOAI3402143 as a promising candidate for LUAD therapy, particularly for patients with limited targeted options or acquired resistance.