Bioactive Materials
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2025
·
IF 20.3
Jiabin Zhang,Xiaodie Chen,Yurong Chai,Yuanyuan Jin,Fenfang Li,Chenya Zhuo,Yanteng Xu,Haixia Wang,Enguo Ju,Yeh-Hsing Lao,Xi Xie,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low in-vivo integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.
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American Journal of Cancer Research
·
2022
·
IF 5.942
Guangyu Cheng,Lin Li,Qingjie Li,Shulin Lian,Hongbo Chu,Yunlu Ding,Chikun Li,Yan Leng
Multi-drug resistance remains a critical issue in cancer treatment that hinders the effective use of chemotherapeutic drugs. The active components of traditional Chinese medicine have been applied as adjuvants to accentuate the anticancer properties of conventional drugs such as cisplatin. However, their application requires further validation and optimization. This study explored the anticancer activity of β-elemene, a natural component of traditional Chinese medical formulations. The effect of β-elemene on the anticancer properties of cisplatin was evaluated in A549 and NCI-H1650 lung cancer cells. Cell apoptosis, stem-like properties, glucose metabolism, multi-drug resistance, and PI3K/AKT/mTOR activation were assessed via flow cytometry, tumorsphere formation, and western blotting. The target genes of β-elemene were predicted using bioinformatics tools and validated in both cell lines. A xenograft model of lung cancer was established in nude mice to evaluate the combined effects of β-elemene and cisplatin in vivo . We found that β-elemene acted synergistically with cisplatin against non-small cell lung cancer cells by promoting apoptosis and impairing glucose metabolism, multi-drug resistance, and stemness maintenance. These effects were mediated by the inhibition of PI3K/AKT/mTOR activation. Bioinformatics analysis revealed that RB1 and TP53 are common target genes associated with lung cancer and β-elemene. The anti-tumorigenic properties of β-elemene were confirmed in vivo , wherein β-elemene, along with cisplatin, significantly suppressed tumor growth in a mouse xenograft model of non-small cell lung cancer. As such, β-elemene acted as an inhibitor of PI3K/AKT/mTOR signaling and enhanced the anticancer effect of cisplatin by targeting tumor metabolism, chemoresistance, and stem-like behavior. Thus, β-elemene is an effective anticancer adjuvant agent with potential clinical applications.
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American Journal of Translational Research
·
2019
·
IF 3.266
Zhongyue Huang,Huijie Gu,Xiaofan Yin,Long Gao,Kunxi Zhang,Yiming Zhang,Jun Xu,Liang Wu,Jingbo Yin,Lei Cui
Microspheres have gained immense popularity in bone tissue engineering because of their unique properties as injectable scaffolds for bone tissue regeneration. Herein, we evaluated the feasibility of using poly (γ-benzyl-L-glutamate) (PBLG) microspheres for bone engineering by examining the attachment, proliferation, and osteogenic differentiation of adipose-derived stem cells (ASCs) in vitro and the use of PBLG microspheres in healing non-union in vivo . Scanning electron microscopy and fluorescent 3, 30-dioctadecyloxacarbocyanine perchlorate-labeling were performed to study the attachment and growth of ASCs to the PBLG microspheres, and a DNA assay was performed to quantify cell proliferation with time. Osteogenic differentiation of ASCs cultured on the PBLG microspheres was assessed by determining alkaline phosphatase expression and extracellular calcium deposition, which was further confirmed by real-time polymerase chain reaction for osteogenesis-related genes. Femoral non-union were created in mouse models and filled with ASCs/PBLG microspheres in vivo . The results showed that ASCs attached, spread, and showed good osteogenic differentiation on the PBLG microspheres in vitro . Moreover, the ASCs/PBLG microspheres could repair the mouse femoral non-union in vivo . Thus, PBLG microspheres have good biocompatibility and cytocompatibility and are potentially useful as an injectable scaffolds for bone tissue engineering.
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Journal of Bionic Engineering
·
2024
·
IF 4.9
He Lizhe,Huang Yuye,Gu Jiafei,Liu Xiaoling,Yin Jun,Gao Xiang
With an elemental composition similar to bone mineral, and the ability to release phosphorus and calcium that benefit bone regeneration, Calcium Phosphate Glass (CPG) serves as a promising component of bone tissue engineering scaffolds. However, the degradation of CPG composites typically results in increased acidity, and its impact on bone-forming activity is less studied. In this work, we prepared 3D-printed composite scaffolds comprising CPG, Poly-ε-caprolactone (PCL), and various Magnesium Oxide (MgO) contents. Increasing the MgO content effectively suppressed the degradation of CPG, maintaining a physiological pH of the degradation media. While the degradation of CPG/PCL scaffolds resulted in upregulated apoptosis of Rat Bone Marrow-derived Stem Cells (rBMSC), scaffolds containing MgO were free from these negative impacts, and an optimal MgO content of 1 wt% led to the most pronounced osteogenic differentiation of rBMSCs. This work demonstrated that the rapid degradation of CPG impaired the renewability of stem cells through the increased acidity of the surrounding media, and MgO effectively modulated the degradation rate of CPG, thus preventing the negative effects of rapid degradation and supporting the proliferation and osteogenic differentiation of the stem cells.
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Bioengineering-Basel
·
2024
·Vol. 11
·期 8
·772
·
IF 3.8
Zhiqiang Tai,Jiashang Liu,Bixue Wang,Shu Chen,Changsheng Liu,Xi Chen
The impact of traumatic spinal cord injury (SCI) can be extremely devastating, as it often results in the disruption of neural tissues, impeding the regenerative capacity of the central nervous system. However, recent research has demonstrated that mesenchymal stem cells (MSCs) possess the capacity for multi-differentiation and have a proven track record of safety in clinical applications, thus rendering them effective in facilitating the repair of spinal cord injuries. It is urgent to develop an aligned scaffold that can effectively load MSCs for promoting cell aligned proliferation and differentiation. In this study, we prepared an aligned nanofiber scaffold using the porcine decellularized spinal cord matrix (DSC) to induce MSCs differentiation for spinal cord injury. The decellularization method removed 87% of the immune components while retaining crucial proteins in DSC. The electrospinning technique was employed to fabricate an aligned nanofiber scaffold possessing biocompatibility and a diameter of 720 nm. In in vitro and in vivo experiments, the aligned nanofiber scaffold induces the aligned growth of MSCs and promotes their differentiation into neurons, leading to tissue regeneration and nerve repair after spinal cord injury. The approach exhibits promising potential for the future development of nerve regeneration scaffolds for spinal cord injury treatment.
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Biomaterials Research
·
2025
·
IF 9.6
Anran Li,Cong Chen,Tongjia Zhang,Yuxin Tian,Yifan Cao,Xiaoming Zhao,Liping Wang
Human umbilical cord mesenchymal stem cell extracellular vesicles (hucMSC-EVs) exhibit remarkable potential for alleviating type 2 diabetes mellitus (T2DM). However, the role of hucMSC-EVs in T2DM, particularly concerning oxidative damage to pancreatic β cells, remains underexplored. This study utilized a high-fat diet and streptozotocin (STZ)-induced T2DM mouse model and an STZ-induced INS-1 cell damage model to investigate the effects and mechanisms of hucMSC-EVs. In the T2DM mouse model, hucMSC-EVs effectively lowered blood glucose levels, improved lipid metabolism disorders, and preserved liver function. Moreover, hucMSC-EVs enhanced insulin sensitivity and mitigated oxidative damage. Histological analysis confirmed that hucMSC-EVs marked alleviated liver, kidney, and pancreatic tissue damage. In vitro studies demonstrate that hucMSC-EVs enhance glucose absorption and glycogen synthesis in an insulin-resistant HepG2 model and stimulated insulin secretion in INS-1 cells under high-glucose conditions. In the STZ-induced INS-1 oxidative damage model, hucMSC-EVs protect against oxidative damage by increasing antioxidant enzyme activities, reducing reactive oxygen species production, and decreasing cell apoptosis. The effects were partially mediated by the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT and signal transducer and activator of transcription (STAT) signaling pathways, as well as the up-regulation of key antioxidant proteins such as Nrf2, SOD1, and Bcl2. Further research revealed that miR-191-5p, which is enriched in hucMSC-EVs, targets DAPK1 to activate the PI3K/AKT pathway, thereby contributing to the protective effects against oxidative damage. These findings highlight the critical role and underlying mechanisms of hucMSC-EVs in ameliorating metabolic dysfunction in T2DM, particularly the protective effects against oxidative damage, thus providing a novel strategy for the treatment of T2DM.
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Journal of Extracellular Vesicles
·
2024
·Vol. 13
·期 12
·e70028
·
IF 15.5
Qimeng Liu,Tianliang Ma,Zheyu Zhang,Jiangyu Nan,Guanzhi Liu,Yute Yang,Yihe Hu,Jie Xie
The development of strategies for the prevention and treatment of aseptic loosening of prostheses stands as a critical area of global research interest. The pyroptosis of local macrophages triggered by wear particles plays a pivotal role in the onset of periprosthetic osteolysis and subsequent loosening. Extracellular vesicles, carrying the surface components and regulatory molecules of their parent cells, embody the cellular characteristics and biological functions of these progenitors. In a pioneering approach to precisely inhibit the pyroptosis of local macrophages induced by wear particles, we have engineered fused extracellular vesicles (fEV) from M 2 macrophages and human umbilical cord mesenchymal stem cells. These fEV boast the distinctive capability for targeted transport and immune evasion, collectively enhancing the anti‐pyroptosis effect of the therapeutic extracellular vesicles. Our research demonstrates the targeted, significant preventive and therapeutic potential of fEVs against periprosthetic osteolysis prompted by wear particles, highlighting its crucial clinical significance and application prospects. These findings suggest that extracellular vesicle fusion technology heralds a novel paradigm in the design and development of targeted extracellular vesicle‐based drug delivery systems.
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ACS Applied Materials & Interfaces
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2025
·
IF 8.2
Haoyang Liu,Yue Zhu,Weixu Chen,Renwang Sheng,Chuanquan Liu,Yuzhi Sun,Jia Liu,Mingyue Wang,Jun Lu,Jialin Chen,Wei Zhang
The advancement of nanomedicine requires a thorough understanding of the intrinsic bioactivity and molecular interactions of nanomaterials for safe and effective clinical applications, which remains lacking for most currently developed nanomaterials. Here, we uncover the unique intrinsic bioactivity and regulatory mechanisms of carbon-based fullerol nanomaterials through high-throughput molecular analysis and explore their therapeutic potential for tissue regeneration using tissue engineering approaches. Fullerol exhibits intrinsic pro-differentiation and antioxidant properties that enhance the osteogenesis and chondrogenesis of MSCs. Mechanistically, proteomic analysis combined with small-molecule inhibition studies reveals that fullerol is internalized by MSCs via clathrin-mediated endocytosis and activates NRF2 signaling, thereby exerting antioxidant effects that restore impaired MSC viability and differentiation under oxidative stress. Leveraging these unique bioactivities, we develop a fullerol-functionalized hydrogel with feasible physicochemical properties and triple biological functions in antioxidant, pro-osteogenic, and pro-chondrogenic effects and confirm its great regenerative capacity for both cartilage and subchondral bone by promoting structural restoration and improving functional recovery in a rat osteochondral defect model. Our findings offer new insights into the intricate interactions between stem cells and nanomaterials at the cellular and molecular levels and broaden the potential biomedical applications of fullerol for future cartilage and bone regeneration therapies.
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ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Shiyang Wu,Zhen Chai,Yanshen Yang,Rong Ding,Bei Gao,Chen Chen,Siyu He,Zhuofu Zhang,Wanting Wan,Rui Zou
Two-dimensional (2D) models fail to mimic a three-dimensional (3D) environment in studying mechanosensing of stem cells. Here, we present a 3D culture model to investigate how 3D matrix stiffness influences YAP activation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and evaluate the osteogenic potential of hydrogels in vivo. In this study, a 3D culture model with an adjustable matrix stiffness was established. In the in vitro study, first the osteogenic differentiation of hPDLSCs by the expression of OCN, ALP, COL-1, and RUNX-2 was assessed using qRT-PCR, accompanied by ALP staining, and then YAP expression was evaluated by immunofluorescence. In the in vivo study, hPDLSCs, together with gelatin methacrylate (GelMA) hydrogels of different stiffnesses, were implanted into a rat alveolar bone defect model. As matrix stiffness increased, hPDLSCs showed reduced spreading and significantly decreased expression of OCN, ALP, COL-1, RUNX-2, and YAP activation. Specifically, COL-1 expression in the low-stiffness group was 4.3-fold higher than that in the high-stiffness group, and the YAP nuclear/cytoplasmic ratio under low stiffness was 5.5-fold greater than that under high stiffness at day 7. In vivo, the soft-matrix-cell-laden group exhibited more new bone (86.04%) and collagen formation (74.43%) in the defect area than other groups at week 6. Reduced matrix stiffness likely promotes hPDLSC proliferation, spreading, and osteogenic differentiation through YAP activation, and low-stiffness GelMA hydrogels loaded with hPDLSCs significantly enhance alveolar bone regeneration in vivo.
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Nanoscale
·
2016
·Vol. 9
·期 1
·334-340
·
IF 7.76
Meng Yang,Yanlei Liu,Wenxiu Hou,Xiao Zhi,Chunlei Zhang,Xinquan Jiang,Fei Pan,Yuming Yang,Jian Ni,Daxiang Cui
Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer. Our results showed that the tumor cells were efficiently killed by the heat generated from the gold nanorods, and the iPS cells ultimately died due to the action of MMC seven days after the photothermal treatment. This suggested that pre-treated iPS cells with MMC can be used as a novel and safe approach for targeted tumor therapy. This paves the road for clinical translation in the future.
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CELL CYCLE
·
2021
·
IF 4.534
Zhensong Jiang,Jianru Zhang
EXs (Exosomes) secreted by mesenchymal stem cells (MSCs) have the potential to treat spinal cord injury (SCI), this study aimed to further explore the therapeutic effect of EXs on SCI. Firstly, EXs were extracted from MSCs and analyzed with a transmission electron microscope. Next, MSCs with or without the miR-145-5p plasmid were injected into the SCI rat model, and then rat damage was evaluated by BBB score, HE staining and Nissl staining. And then Luciferase experiment verified the targeting relationship between miR-145-5p and TLR4. Furthermore, LPS-induced PC12 cells were established and incubated with Dil-labeled MSC-EXs to explore their effects on cell viability, apoptosis and inflammation through MTT, flow cytometry and ELISA, respectively. In addition, expressions of TLR4/NF-κB signaling pathway related factors were measured by qRT-PCR and Western blot. The results showed that after MSCs were successfully isolated, the existence of EXs in MSCs was confirmed. Moreover, MSC-EXs containing miR-145-5p improved functional recovery and reduced histopathological injury and inflammation in SCI rats. And MSC-EXs promoted miR-145-5p expression in spinal cord tissue and inhibited TLR4/NF-κB pathway activation in SCI rats. MSC-EXs inhibited LPS-induced inflammatory response and activation of the TLR4/NF-κB pathway in PC12 cells. In addition, we also found that miR-145-5p specifically targeted TLR4. TLR4 overexpression significantly reversed the effect of EX-miR-145-5p on maintaining PC12 cell viability, inhibiting apoptosis and inflammatory response, and activating TLR4/NF- κB pathway. In conclusion, mesenchymal stem cell-derived EXs containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway.
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Frontiers in Cellular Neuroscience
·
2021
·
IF 5.505
Wang Lei,Gu Sujie,Gan Jinlu,Tian Yi,Zhang Fangcheng,Zhao Hongyang,Lei Deqiang
Spinal cord injury (SCI) is a devastating event characterized by severe motor, sensory, and autonomic dysfunction. Currently, there is no effective treatment. Previous studies showed neural growth factor (NGF) administration was a potential treatment for SCI. However, its targeted delivery is still challenging. In this study, neural stem cells (NSCs) were genetically modified to overexpress NGF, and we evaluated its therapeutic value following SCI. Four weeks after transplantation, we observed that NGF-NSCs significantly enhanced the motor function of hindlimbs after SCI and alleviated histopathological damage at the lesion epicenter. Notably, the survival NGF-NSCs at lesion core maintained high levels of NGF. Further immunochemical assays demonstrated the graft of NGF-NSCs modulated the microenvironment around lesion core via reduction of oligodendrocyte loss, attenuation of astrocytosis and demyelination, preservation of neurons, and increasing expression of multiple growth factors. More importantly, NGF-NSCs seemed to crosstalk with and activate resident NSCs, and high levels of NGF activated TrkA, upregulated cAMP-response element binding protein (CREB) and microRNA-132 around the lesion center. Taken together, the transplantation of NGF-NSCs in the subacute stage of traumatic SCI can facilitate functional recovery by modulating the microenvironment and enhancing endogenous neurogenesis in rats. And its neuroprotective effect may be mediated by activating TrkA, up-regulation of CREB, and microRNA-132.
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