Advanced Science
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2026
·
IF 14.1
Lijun Li,Hao Zhang,Lingtong Sun,Yingfeng Su,Yang Xu,Jian Huang,Jingchao Wen,Jinjin Zhu,Jianjun Ma,Wenbin Xu
Critical-sized bone defects remain a highly challenging clinical problem due to insufficient intrinsic self-healing capacity. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have emerged as promising cell-free therapeutic candidates for bone regeneration, owing to their paracrine effects in regulating bone regeneration-related processes. However, enhancing exosome bioactivity via biomimetic preconditioning and developing efficient delivery vectors remain key bottlenecks in this field. Herein, we developed a synergistic bone regenerative system composed of biomimetic preconditioned BMSC-derived exosomes (BioPre-Exos) and injectable porous polydopamine (PDA)-modified gelatin methacryloyl (GelMA) microspheres. The biomimetic preconditioning strategy adopted 3% hypoxia combined with 3D GelMA microsphere culture, mimicking the bone marrow microenvironment to regulate BMSC functions and significantly boost exosome bioactivity. Functional experiments verified that BioPre-Exos robustly promoted BMSC migration, osteogenic differentiation, angiogenesis, and macrophage polarization toward an anti-inflammatory phenotype in vitro. Furthermore, in a rat femoral condyle defect model, the composite system markedly improved neovascularization density and bone volume fraction, thus achieving efficient vascularized bone regeneration. These findings indicate that this cell-free biomimetic synergistic delivery system holds great application potential in the clinical treatment of bone defects.
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高影响因子
Cell Reports Medicine
·
2026
·Vol. 7
·期 3
·
IF 14
Xudong Li,Shiyu Zuo,Yanli Zhang,Zexing Liu,Na Shen,Qingqing Ma,Mingxia Sun,Binglei Zhang,Mengjia Li,Hong Huang,Mengya Gao,Zhenghua Huang,Huifang Zhao,Yilin Chen,Fengcai Gao,Wenjuan Fan,Zhen Zhang,Yuhan Hu,Yu An,Siyue Li,Miao Liu,Yupeng Liu,Yuxuan Liu,Chaoge Li,Yiguo Zhang,Yingmei Li,Weijie Cao,Fang Wang,Yongping Song,Linping Xu,Zhilei Bian,Wei Li
Eradicating leukemia stem cells (LSCs) and overcoming tyrosine kinase inhibitor (TKI) resistance is urgent for chronic myeloid leukemia (CML) treatment. We find that F-box protein 3 (FBXO3) is highly upregulated in CD34 + CML stem cells from TKI-resistant patients and identify it as an innovative CML-LSC marker via single-cell RNA sequencing (scRNA-seq). FBXO3 deficiency induces apoptosis and reduces proliferation of CML cell lines and LSCs in vitro and in vivo , with minimal effects on normal CD34 + hematopoietic stem cells (HSCs). Mechanistically, FBXO3 interacts with DUSP9 to promote its ubiquitination and activate the MAPK pathway, critical for CML cell activity. DUSP9 knockdown partially reverses FBXO3-deficiency-mediated LSC elimination. Furthermore, FBXO3 inhibitor monotherapy or combination with imatinib effectively eradicates CML-LSCs, overcomes TKI resistance, and spares normal hematopoiesis. Collectively, our findings highlight FBXO3’s role in CML progression and support combining FBXO3 inhibitors with TKIs for durable LSC elimination.
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TISSUE & CELL
·
2026
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IF 3.1
Xuan He,Dan Liang,Xinyi Zhao,Kaixin Liu,Zicheng Zhang,Meiling Li,Xuemeng Ma,Wenxia Chen,Xiaoyi Zhong
Objective This study investigates the influence of Notoginsenoside R1 (NGR1) on the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and its potential application in direct pulp capping, utilizing both in vitro and in vivo models. The results aim to provide a theoretical basis for expanding the clinical use of NGR1. Methods hDPSCs were isolated, cultured and characterized in vitro. The effects of varying concentrations of NGR1 (0, 50, 100, 200 μg/ml) on cell proliferation and migration were evaluated using the CCK-8 and Transwell assays, respectively. The effect of NGR1 on odontogenic differentiation was evaluated by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, as well as RT-PCR to detect the mRNA expression levels of ALP and DSPP. A direct pulp capping model was established in adult dogs. The experimental group was rinsed with 100 μg/ml NGR1 solution before capping, and samples were collected at 1, 4, 8, and 12 weeks. Micro-CT scanning and H&E staining were used to analyze reparative dentin and pulp morphology. Additionally, RNA-Seq of hDPSCs treated with 100 μg/ml NGR1 was conducted, followed by DEG screening, GO/KEGG enrichment, GSEA, and PPI analyses, RT-PCR and IHC were used to verify the DEGs. Results NGR1 promotes hDPSCs proliferation, migration, and odontogenic differentiation. In vitro experiments demonstrated that NGR1 enhanced ALP activity and mineralized nodule formation. Both the 100 μg/ml and 200 μg/ml groups significantly promoted the mineralization of hDPSCs. RT-PCR results showed that mRNA expression levels of ALP and DSPP were significantly upregulated in NGR1-treated groups. Animal experiments revealed the formation of continuous, uniform, and thickened reparative dentin over time in both the Control(0 μg/ml) and NGR1-treated groups. H&E staining showed dentin bridges at 4, 8, and 12 weeks in both Control(0 μg/ml) and NGR1 groups. Histological observations suggested that reparative dentin in the NGR1-treated groups appeared to have numerous, regularly arranged dentinal tubules and a compact architecture, whereas the Control(0 μg/ml) groups showed a relatively less organized structure. RNA-Seq results identified 50 upregulated DEGs, including the dentin-related gene S100A9. These DEGs were enriched in the complement and coagulation cascades, cytokine-cytokine receptor interaction, Staphylococcus aureus infection, and tuberculosis pathways. PPI analysis identified SPRR1A, SPRR1B, and SPRR3 as potential hubs. RT-PCR and IHC confirmed that the expression trends of the differentially expressed genes were consistent with the sequencing results. Conclusion NGR1 promotes the proliferation, migration, and odontogenic differentiation of hDPSCs, with the 100 μg/ml concentration providing an optimal balance between proliferative and pro-differentiation effects. In vivo, NGR1 improves the microstructural quality of reparative dentin. Transcriptomic analysis revealed upregulation of S100A9 and enrichment of repair-related pathways, which may serve as a basis for future mechanistic studies.
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Stem Cell Research & Therapy
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2026
·Vol. 17
·期 1
·123
·
IF 7.8
Du Mengxian,Guo Fengyi,Liu Xinna,Zhang Shiqi,Zhang Di,Qiu Leyi,Zhang Jingyang,Li Baoqiang,Yuan Huiping
Background Normal tension glaucoma (NTG) causes progressive retinal ganglion cell (RGC) loss without elevated intraocular pressure, and currently lacks effective neuroprotective therapies. OPTN(E50K) mutation, a pathogenic gene of NTG, compromises paracrine trophic capacity in bone marrow (BM) stem cells. Allogeneic young BM stem cells can provide trophic support and exhibit therapeutic potential; however, their clinical application is limited by immunogenic rejection and tumorigenic risks, prompting a renewed interest in rejuvenate autologous BM stem cells strategy. Methods To address these challenges, we developed a composite chitosan-rapamycin (RAPA) carbon dots (CRCD) to restore the reparative potential of autologous BM stem cells. BM stem cells from aged OPTN(E50K) mice were isolated, clustered and treated with CRCD before validated their changes of neurotrophic factors expression as well as oxidative stress and autophagy indicators. Then we assessed their impact on co-cultured retinas in vitro. Transplantation were performed into lethally irradiated age-matched OPTN(E50K) hosts with CRCD-pretreated autologous BM stem cells via tail vein injection, and generated stable chimeric models. Neurotrophic factors and neuron apoptosis analyses were performed, followed by the visual behavioral tests. Results Our results demonstrated that CRCD pretreatment enhanced autophagy, reduced oxidative stress, and augmented paracrine neurotrophic release. In vitro, these cells reduced retinal ganglion cell apoptosis and promoted neurotrophic factor expression in co-cultured retinal explants. In vivo, comparative analysis revealed that CRCD intervention significantly elevated neurotrophic factor expression in retinal tissues compared to RAPA-treated and untreated chimeras. Functional assessments further confirmed superior visual performance in CRCD-Sca-1 + chimeras, correlating with improved RGC survival. Conclusion These findings suggest that CRCD improved paracrine neurotrophic support of autologous BM stem cells by enhancing their autophagy and paracrine functions, leading to structural and functional rescue of the glaucomatous retina. This approach offered a clinically relevant strategy for NTG, providing sustained neuroprotection while avoiding the risks of allogeneic transplantation and repeated intravitreal drug delivery. Graphical The alternative text for this image may have been generated using AI.
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PLoS One
·
2025
·Vol. 20
·期 6
·e0325704
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IF 2.6
Yuelong Zhang,Xunshan Ren,Huangming Zhuang,Huajie Li,Miradj Siddick Adam,Rongling Feng,Junming Zhu,Panghu Zhou
Osteoarthritis (OA), characterized by synovial inflammation, articular cartilage degeneration, and structural changes of subchondral bone and periarticular tissues, represents a major unmet clinical challenge. Targeting senescent chondrocytes has emerged as a promising therapeutic strategy of OA. Human umbilgratical cord mesenchymal stem cells (hUCMSCs) have shown potential in OA treatment through paracrine mechanisms, but their clinical translation is limited by challenges in cell viability control and safety concerns. hUCMSCs decellular extracellular matrix (hUCMSCs-dECM) can target senescent chondrocytes to alleviate senescence in OA. Stimulator of interferon gene (STING) can promote chondrocyte senescence in OA through the activation of NF-κB signaling, and inhibition of STING may provide a novel approach for OA treatment. Here, we demonstrated that hUCMSCs-dECM attenuated chondrocyte senescence in vivo and in vitro by inhibiting the STING-NF-κB pathway, which would provide a novel approach for OA treatment.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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IF 8.5
Shun Yu,Ying Luo,Xiaoli Jia,Pan Du,Zili Sun,Yuying Wang,Guozhong Lyu,Chenyang Liu
Our previous research established that treatment with IFN-γ and TNF-α (IT) significantly enhanced the paracrine activity of MSCs, resulting in a more effective wound healing response when applied to the wound surface with supernatant from IT-stimulated MSCs (S-IT MSCs). While S-IT MSCs hold promise for advancing wound healing therapy, challenges remain in developing an approach that enhances therapeutic efficacy and simplifies administration. This study proposed a scaffold composed of sericin, known for its skin regeneration properties, to load S-IT MSCs, designated as Se + S-IT MSCs, for the protection of bioactive factors. Additionally, whether Se + S-IT MSCs exhibit a superior effect on wound healing was investigated using a rat total skin excision model. Results indicated that Se + S-IT MSCs outperformed silk sericin loaded with MSC supernatant (Se + S-MSCs) in promoting migration, proliferation, and activation of HUVECs, HaCaTs, macrophages, and HDFs. Furthermore, Se + S-IT MSCs significantly promoted macrophage polarization toward the M2 phenotype, potentiated vascularization and re-epithelialization, and enhanced collagen deposition. These effects collectively accelerated wound healing in vivo in rats. This study highlights the potential of Se + S-IT MSCs to facilitate rapid and effective wound healing, with silk sericin scaffolds serving as efficient carriers to expedite the process.
研究领域:
再生医学
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组织工程
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免疫学
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FOOD RESEARCH INTERNATIONAL
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2025
·
IF 8
Duoduo Zhang,Kunying Chen,Yongkang Yu,Ruting Feng,Steve W. Cui,Xingtao Zhou,Shaoping Nie
Metabolites of dietary fibers which consist of non-digestible carbohydrates (usually as plant-based polysaccharides) exert many benefits on gastrointestinal health. Previous studies proved that polysaccharides can change intestinal metabolic pathways, increase metabolite levels and alleviate intestinal inflammation. Our previous studies have shown that polysaccharide from Aloe vera gel (AGP) alleviated intestinal barrier dysfunction. However, whether intestinal protective function of AGP was related to metabolites need further exploration. Therefore, the effects of AGP on intestinal metabolites and the relevant mechanisms for subsequent mitigation of intestinal damage was investigated in this work. Metabolomics analysis results showed that AGP promoted tryptophan metabolism to 5-hydroxytryptamine (5-HT). Intriguingly, antibiotics treatment decreased the expression of tryptophan hydroxylase 1 (TPH1) in the intestinal epithelium of mice, and TPH1 inhibitor (PCPA) down-regulated 5-HT level in colonic contents, proving that AGP up-regulated TPH1 expression in the intestinal epithelium by restoring intestinal microbiota homeostasis, thus promoted the intestinal tryptophan metabolism to 5-HT. Combination of bioinformatics analysis of RNA-sequencing (RNA-Seq) in mice colon and the reported relationship among “5-HT, Htr4 (one of the 5-HT receptors), Kit + goblet cells, canonical Wnt pathway and intestinal stem cells (ISCs)” guided the confirmation of related mechanism in intestinal organoids (IOs) that 5-HT regulated ISCs function and intestinal barrier via Htr4-Kit-Wnt3 axis. Overall, AGP promoted 5-HT production to alleviate intestinal injury. This study revealed the effects of polysaccharides on intestinal health, which was critical and may provide new insights for the reasonable selection of dietary fiber to prevent intestinal inflammation and maintain intestinal function.
研究领域:
胃肠病学
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营养学
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分子生物学
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高影响因子
CELL BIOLOGY AND TOXICOLOGY
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2025
·Vol. 41
·期 1
·1-29
·
IF 5.9
Tian Sirui,Yu Haiyang,Yang Ruoxuan,Wang Heshi,Zhao Baohong,Wang Danning
Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies. Graphical 1. IGFBP3 enhances ADSC function in STI repair by activating ITGB1 and ERK pathways. 2. High IGFBP3 expression promotes ADSC differentiation into epithelial cells, improving tissue regeneration. 3. Single-cell multiomics and 3D bioprinting validate IGFBP3’s role in advancing STI treatment. 4. Findings present IGFBP3 as a promising molecular target for clinical STI therapy.
研究领域:
再生医学
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分子生物学
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生物材料学
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ACS Nano
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2025
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IF 16
Fan Chen,Wenzhe Wang,Hengxin Zhao,Zian Zhang,Nanyu Pang,Yijie Tang,Tian Wang,Chang Liu,Zhenchao Huang,Feiyu Mou,Chaoqun Yu,Haining Zhang
Intra-articular drug injection is an effective treatment for osteoarthritis (OA). However, the rapid clearance of drugs from the joint cavity results in low drug utilization and suboptimal therapeutic outcomes. This study describes MXene-based cartilage-adhesive microspheres for photothermal-controlled hydrophobic drug release and bone marrow mesenchymal stem cell (BMSC) delivery. Nano cationic amylose (NCA) was obtained by modifying amylose with glycidyltrimethylammonium chloride (GTAC), and hydrophobic drug Kartogenin (KGN) was encapsulated in the hydrophobic helical cavity of NCA through ultrasonic treatment, resulting in nano cationic amylose@KGN complexes (NCA@KGN). HAMA/MXene-NCA@KGN (H/M-NCA@KGN) microspheres were prepared using a microfluidic device. These microspheres exhibited excellent biocompatibility, effectively adhered to the cartilage surface, and carried BMSCs. H/M-NCA@KGN microspheres demonstrated photothermal-controlled release of the hydrophobic drug KGN. Notably, KGN promoted the differentiation of BMSCs into chondrocytes, thereby improving the loss of extracellular matrix in joint cartilage. Additionally, appropriate thermal stimulation induced the expression of heat shock protein 70 (HSP70) in OA chondrocytes, providing a protective effect and delaying the progression of OA. H/M-NCA@KGN microspheres enable controlled hydrophobic drug release and stem cell delivery for potential OA treatment applications.
研究领域:
生物医学工程
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药学
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组织工程
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高影响因子
Cellular Reprogramming
·
2014
·Vol. 16
·期 5
·379-391
·
IF 2.345
Chao Yang,Liang Sun,Xinghan Li,Li Xie,Mei Yu,Lian Feng,Zongting Jiang,Weihua Guo,Weidong Tian
Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.
研究领域:
干细胞生物学
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神经科学
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再生医学
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高影响因子
Nano Materials Science
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2024
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IF 12.6
Ming Deng,Geliang Hu,Fan Liang,Qi Liao,Wanjun Ding,Bin He,Jianghua Ming,Hui Huang,Junqi Liu,Zhaohong Kong,Ping Xie
Objective To investigate the repair of spinal cord injury (SCI) in rats using 3D bioprinted decellularized extracellular matrix (dECM) hydrogel, neural stem cells (NSCs), and TGF-β1 monoclonal antibody. Methods The spinal cord-derived dECM hydrogel (SC-dECM-gel) was optimized for 3D printing. Rheological tests established a 3 % concentration as optimal. In vitro tests assessed the effects of TGF-β1 monoclonal antibody on NSC viability and differentiation. A rat SCI model was treated with the printed gel, and recovery was monitored using the Basso-Beattie-Bresnahan test and evoked potentials. Results The 3 % SC-dECM-gel showed superior rheological properties. TGF-β1 monoclonal antibody enhanced NSC survival and differentiation in vitro. In vivo, the 3D bioprinted gel significantly improved motor function and promoted neuronal regeneration. Conclusion 3D bioprinted SC-dECM-gel loaded with NSCs and TGF-β1 monoclonal antibody effectively restores motor function and promotes regeneration in SCI rats, offering a promising approach for SCI treatment.
研究领域:
再生医学
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神经科学
·
生物材料学
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高影响因子
Journal of Biomaterials and Tissue Engineering
·
2017
·Vol. 7
·期 9
·876-881
·
IF 1.383
Dai Liming,Zhu Hongtao,Zhang Chaoguang,Liu Tao,Wang Yi
In this paper, the biocompatible chitosan/gelatin scaffolds at different chitosan/gelatin ratios were fabricated by a facile method. The important physical parameters of the scaffolds, including density, porosity and tensile strength were measured. MSCs were transfected to introduce
brain-derived neurotrophic factor (BDNF) gene into the cells. To evaluate the bioactivity of the scaffolds, the gene-modified BDNF-MSCs were cultivated on the scaffolds, and the cell proliferation and BDNF expression level were determined.
研究领域:
生物材料
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组织工程
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神经科学
·
干细胞生物学
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高影响因子
危险品化学品经营许可证（带存储）