EXPERIMENTAL CELL RESEARCH
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2025
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IF 3.5
Yongna Zhu,Xiang Ge,Zhi Chen,Tingting Chen,Yue Wu,Hebao Wen,Zeyu He,Caiyun Ma
Stem cells from the apical papilla (SCAPs) show strong odontogenic ability and can form root dentin. However, the underlying mechanisms that control the odontogenic differentiation of SCAPs in an inflammatory environment need further exploration. In the present study, we explored the regulatory role of METTL3 in the differentiation of SCAPs originating from tooth with apical periodontitis. Stem cells from the apical papilla derived from healthy teeth (SCAPs) and teeth with apical periodontitis (AP-SCAPs) were successfully isolated and cultured. The expressions of tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) were higher in AP-SCAPs. A decrease in METTL3 expression accompanied the decreased osteo-/odontogenic differentiation ability of AP-SCAPs. Exploring the role of METTL3 on the osteo-/odontogenic differentiation of AP-SCAPs revealed that overexpression of METTL3 upregulated the odontogenic ability of AP-SCAPs. However, silencing METTL3 exerted the opposite effect. Overexpression of METTL3 suppressed the expression of TNF-α and IL-6 in AP-SCAPs, whereas knockdown of METTL3 in these cells enhanced TNF-α and IL-6 expression. METTL3 regulates the osteo-/odontogenic differentiation of SCAPs and modulates their inflammatory response. Furthermore, overexpression of METTL3 upregulated the methylation level, mRNA, and protein expression of nuclear factor-IC (NFIC) during mineralization induction. NFIC silencing attenuated osteo-/odontogenic differentiation of METTL3-overexpressed AP-SCAPs. In conclusion, METTL3-mediated-m6A upregulated the odontogenic differentiation of AP-SCAPs via NFIC. This paper elucidates a novel mechanism regulating the odontogenic differentiation of AP-SCAPs, and METTL3 may be a new target for regenerative endodontic treatment.
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Cell Communication and Signaling
·
2024
·Vol. 22
·期 1
·1-22
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IF 8.2
Wu Xiao,Tang Ying,Lu Xinxing,Liu Yigao,Liu Xu,Sun Qin,Wang Lu,Huang Wei,Liu Airan,Liu Ling,Chao Jie,Zhang Xiwen,Qiu Haibo
Background Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms. Methods EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms. Results Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs. Conclusions This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
Xuezhong Cui,Jing Li,Yuemin Wang,Tong Sun,Jie Weng,Zhiqiang Li,Jianshu Li,Xingyu Chen
In recent decades, porous titanium (Ti) bone-engineered scaffolds have emerged as a promising biomaterial for bone defect repair due to their excellent biocompatibility and mechanical properties. However, the limited bioactivity on the surface of the porous scaffold hinders osteogenesis and osseointegration, thereby restricting its further application. In this study, we utilized surface-initiated atom transfer radical polymerization to prepare a zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) modified bioactive coating on the surface of a 3D-printed porous Ti scaffold. Additionally, exosomes derived from bone mesenchymal stem cells (BMSCs) were introduced into the scaffold surface via specific interactions between choline phosphate and phosphatidylcholine (CP-PC) on exosomes. In vitro studies for ossification and transcriptome analysis have shown that the exosome bioactive coating on a Ti scaffold enhances the proliferation of BMSCs, their osteogenic activity, and the expression of osteogenic-related genes. Furthermore, in vivo study results from hard tissue sectioning and microcomputed tomography indicate that the bioactive Ti scaffold significantly promotes new bone formation after 4 and 12 weeks of implantation in rabbit femoral defects. Overall, this study showcases the potential of the exosome-based Ti scaffold to enhance osteogenic activity, offering a novel strategy for cell-free bone tissue regeneration with significant therapeutic implications.
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CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Tianyi Shao,Mingzhe Yan,Rui Liu,Yanming Zhang,Banghui Wang,Yifei Li,Yuxin Liu,Danxia Li,Lixin Jin,Bingcheng Yi,Qihui Zhou
Acellular cellulose-based biomaterials hold promising potential for treating bladder injuries. However, the compromised cellular state surrounding the wound impedes the complete reconstruction of the bladder. This necessitates the development of a bio-instructive cellulose-based biomaterial that actively controls cell behavior to facilitate effective bladder regeneration. To develop such an advanced cell-free scaffold, a bacterial cellulose (BC) substrate is elaborately modified through layer-by-layer assembly of heparin and collagen (H/C), followed by glutaraldehyde crosslinking, resulting in a biomimetic nanofibrous scaffold with optimized mechanical properties and reduced salt crystal deposition. Critically, the scaffold is functionalized with anti-CD29 antibodies, enabling selective in situ capture of urine-derived stem cells (USCs) without compromising their viability. The (H/C)-modified BC scaffold exhibits exceptional swelling and extracellular matrix-like architecture, which mirrors the natural bladder environment. Fluorescent immunostaining confirms uniform antibody grafting, confirming the efficacy of this modified biomaterial in attracting and retaining USCs. Overall, this study introduces a BC-based scaffold that has been innovatively modified with CD29, enabling the selective capture of USCs from urine. This innovative acellular biomaterial represents a promising acellular strategy to address the challenges posed by compromised cellular conditions during bladder reconstruction, offering a novel avenue for regenerative bladder therapies.
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Materials Today Bio
·
2025
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IF 10.2
Jialu Weng,Yizhang Chen,Yuhan Zeng,Wenzhang Jin,Ying Ji,Wa Zhang,Shunfu Wang,Haobing Li,Meilin Yi,Xiaoying Niu,Xuchen Deng,Jiancheng Huang,Xiang Su,Lulu Chen
Diabetic wound healing is constrained by various factors, including chronic inflammation, sustained oxidative stress, impaired angiogenesis, and abnormal wound microenvironments. Exosomes derived from mesenchymal stem cells (MSC-exo) contain a wealth of bioactive substances that play a positive role in promoting diabetic wound healing. Plant-derived exosomes, as a novel therapeutic approach, are continuously being explored. Momordica charantia (MC) has been shown to possess blood glucose-lowering effects, and its exosomes are of significant relevance for treating diabetic wounds. However, direct application of exosomes to wounds faces challenges such as poor stability and short retention time, limiting their therapeutic effectiveness and clinical applicability. Encapsulating exosomes in hydrogels is an effective strategy to preserve their bioactivity. In this study, we fabricated a hydrogel loaded with MSC-exo and MC exosomes (MC-exo) by photopolymerization of methacrylated gelatin (GelMA) and dopamine (MEMC-Gel). The resulting MEMC-Gel exhibited favorable mechanical properties, adhesion, degradability, absorbency, and biocompatibility. In vitro, MEMC-Gel demonstrated the ability to resist inflammation, counter oxidative stress, promote fibroblast migration, support endothelial cell angiogenesis, and regulate macrophage polarization. In a diabetic mouse wound model, MEMC-Gel accelerated wound healing by inhibiting inflammation and oxidative stress, modulating macrophage immune responses and hyperglycemia within the microenvironment, promoting angiogenesis, and enhancing epithelialization. In conclusion, MEMC-Gel is an outstanding hydrogel dressing that synergistically promotes repair by loading MSC-exo and MC-exo, significantly accelerating diabetic wound healing through multiple mechanisms. This multifunctional hydrogel, based on exosomes from two different sources, provides an innovative therapeutic strategy for diabetic wound repair with broad clinical application potential.
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
Lixin Ding,Qian Guo,Ya’nan Ren,Pei Wang,Yongxiang Pan,Jin Ding,Feng Wang,Zhi Yang,Hua Zhu
Extracellular vesicles (EVs) act as carriers that transfer molecules between donor and recipient cells, thereby altering the phenotype and function of the latter. EVs derived from mesenchymal stem cells (MSCs) inherit the homing ability of their parent cells to tumor sites. We speculate that MSC-derived EVs labeled with the isotope zirconium-89 ([89Zr]Zr) will accumulate within tumors and have the potential for tumor location via positron emission tomography (PET) imaging. Here, as a proof of concept, we used [89Zr]Zr-labeled human umbilical cord MSC (hucMSC)-derived EVs to characterize the homing of EVs to tumor regions via PET imaging. The uptake of [89Zr]Zr-DFO-hucMSC-EVs by 4T1, H292, and FaDu cells increased in a time-dependent manner. [89Zr]Zr-DFO-hucMSC-EVs were rapidly cleared from the blood circulation, showing a 2-phase exponential decay with a biodistribution half-life of 0.46 h and an elimination-phase half-life of 11.87 h. At 24 h postinjection, [89Zr]Zr-DFO-hucMSC-EVs were mainly distributed in the liver (10.39 ± 0.52%ID/g) and, to a lesser extent, in the spleen (9.87 ± 0.87%ID/g). PET imaging in tumor-bearing mouse models revealed persistently high tumor accumulation. The projected effective dose for an adult human female was low and was 0.084 mSv/MBq. There was no obvious normal tissue toxicity following the administration of excessive radioactivity. In summary, these studies demonstrate the potential feasibility of using the [89Zr]Zr-DFO-hucMSC-EV tracer for noninvasive visualization of tumor lesions.
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ACS Nano
·
2025
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IF 16
Yanyan Zhang,Huimin Zheng,Yu Zhao,Cong Du,Jian Zhang,Jinying Liu,Shengjie Jiang,Yan Wei,Chuan-Liang Feng
Chirality is a pivotal determinant in stem cell differentiation, yet discerning the individual effects of chirality across different scales within native three-dimensional (3D) environments remains challenging. Here, a strategy is employed using nanostructures with controlled chirality to precisely assess the impact of molecular and supramolecular chirality on mesenchymal stem cell (MSC) osteogenic differentiation. We synthesized two pairs of enantiomers, l/d-phenylalanine (l/D-Phe) and l/d-1-naphthylalanine (L/D-1-Nap) derivatives, which could form four distinct chiral fibrous hydrogels with different molecular and supramolecular chiralities: L-supP and D-supP (supP indicates supramolecular right-handed helix), and L-supM and D-supM (supM denotes supramolecular left-handed helix). Both experimental and computational analyses reveal that the supramolecular supM/supP helicity is governed by conformational changes in aromatic side chains, switching between outward and inward orientations. Intriguingly, MSCs encapsulated within these chiral fibers displayed osteogenic differentiation that was predominantly influenced by higher-order supramolecular chirality rather than molecular chirality. Specifically, supM-nanofibrils significantly promoted the MSC commitment to the osteoblast lineage, whereas supP-nanofibrils lacked this osteoinductive potential. Additionally, we observed subtle positive and negative modulations of MSC osteogenic differentiation by l- and d-enantiomeric molecular chiralities, respectively. Our study presents a strategy for chiral hydrogel design and delineates how supramolecular chirality surpasses molecular chirality in directing MSC osteogenesis within 3D hydrogels, highlighting the potential of chiral biomaterials in bone tissue engineering.
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Scientific Reports
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2025
·Vol. 15
·期 1
·1-13
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IF 3.9
Chen Juanli,Wei Chuanfei,Zhang Yingchao,Chen Qingfa,Li Xuemei,Zhang Wei,Zhang Xiaoping,Han Fabin
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) plaques, leading to neuronal death. Notably, there are no therapeutically efficacious treatments for this disorder. This study investigates the neuroprotective mechanisms of curcumin. In vitro experiments demonstrated that curcumin significantly promoted the proliferation of neural stem cells (NSCs) derived from E16 mouse embryos. Additionally, in the APP/PS1 transgenic mouse model, curcumin improved cognitive function, as evidenced by a shorter escape latency and increased platform crossing frequency in the Morris water maze test and enhanced novel object recognition. Histological analysis showed that curcumin reduced Aβ accumulation in the hippocampal and cortical regions. Molecular studies revealed that curcumin upregulated the expression of BDNF and enhanced phosphorylation of CREB. Collectively, these findings indicate that curcumin exerts neuroprotective effects through multiple mechanisms, including promoting NSC proliferation, reducing Aβ accumulation, and the potential modulation of the BDNF-CREB signaling pathway.
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·722
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IF 12.6
Ye Leiguang,Zhu Jinying,Wang Xiaoman,Chen Nianhan,Sun Ying,Zeng Xuemei,Liu Shijian,Yan Shuangqian
Overcoming therapy resistance in triple-negative breast cancer (TNBC) requires the effective targeting of cancer stem-like cells (CSCs). TNBC is characterized by hyperactivation of the mevalonate pathway, leading to cholesterol accumulation in CSC membranes, which alters membrane properties, enhances stemness, and restricts both drug penetration and lipid peroxidation-a key driver of ferroptosis. Here, we develop Fe/CDP, a nanoparticle with a Fe 3 O 4 core coated with chondroitin sulfate and loaded with pravastatin, a mevalonate pathway inhibitor, and doxorubicin (DOX). In TNBC mouse models, Fe/CDP selectively targets tumors and CSCs via CD44-chondroitin sulfate interactions, enabling localized drug release. Pravastatin suppresses cholesterol biosynthesis, restoring membrane rigidity and fluidity, thereby reducing CSC stemness, disrupting P-glycoprotein function, and downregulating ALDH1, which enhances DOX sensitivity via the EGFR/Src/HMGCR axis. Moreover, cholesterol depletion facilitates lipid peroxidation, synergizing with Fe 3 O 4 to trigger ferroptosis through CoQ10/GPX4/FSP1 downregulation. By eliminating both bulk tumor cells and CSCs, Fe/CDP provides a cholesterol-modulating strategy to overcome TNBC drug resistance. Graphical
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Molecular Medicine Reports
·
2025
·Vol. 33
·期 1
·1-10
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IF 3.5
Hongwei Xiao,Jianfeng Li,Wei Huang,Yi Qin
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2017
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IF 3.671
Han Yue,Yanqiu Liu,Huanhuan Qu,Kan Ding
Dendrobium officinale Kimura et Migo (Tie-Pi-Shi-Hu), a precious folk medicine exhibiting multiple bioactivities, including antitumor, immune-enhancing and so on. Although evidences showed polysaccharide is one of the major bioactive substances from this herb, several of them were homogenous with fine structures elucidated. In this study, we showed a novel homogeneous heteroxylan obtained from alkali-extracted crude polysaccharide. It composed of arabinose, xylose, glucose and 4- O -methylglucuronic acid (4-MGA) as well as trace amount of rhamnose and galactose in a ratio of 8.9:62.7:8.5:12.3:3.9:3.7. We further showed that it contained a backbone of 1,4-linked β- d -xylan, with branches of 1,4-linked α- d -glucose, 1,3-linked α- l -rhamnose, and terminal-linked α- l -arabinose, β- d -galactose, 4-MGA, and β- d -xylose directly or indirectly attached to C-2 position of glycosyl residues on backbone. The sulfated derivative with substitution degree about 0.9 was prepared according to the chlorosulfonic acid (CSA)-pyridine method. Bioactivity tests suggested that the sulfated polysaccharide could significantly disrupt tube formation and inhibit the migration of human microvascular endothelial cells (HMEC-1) at a low concentration (0.29 μM) in a dose-dependent way without significant cytotoxity.
研究领域:
植物化学
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药理学
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BMC Urology
·
2023
·Vol. 23
·期 1
·1-11
·
IF 2
Pan Gaojian,Jiang Bo,Yi Zhongquan,Yin Jiuhu,Liu Yadong
Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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