Journal of Materials Chemistry B
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2021
·Vol. 10
·期 4
·518-536
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IF 6.331
Zihan Yang,Xichao Wang,Guohai Liang,Anli Yang,Jinming Li
Mesenchymal stem cells (MSCs) have multiple differentiation potentials and their clinical application is limited by controlled cell differentiation and long-term tracing in vivo. Here, we developed an upconversion nanoparticle (UCNP)-based nanoplatform for the photocontrolled chondrogenic differentiation and long-term tracking of MSCs in vivo. The UCNP nanoplatform could convert 980 nm near-infrared (NIR) light into UV/blue light (365/475 nm) and green/red light (545/647 nm) through Tm/Er doping. Then, the upconverted UV/blue light was used to drive the photosensitive molecule azobenzene (azo) that was modified in mesoporous silica to constantly change its conformation to trigger the release of kartogenin (KGN) from the UCNPs to induce the chondrogeni differentiation of MSCs, achieving photocontrolled cell differentiation. Both in vitro and in vivo experiments demonstrated the effective induction of chondrogenic differentiation in MSCs by NIR light with the UCNP nanoplatform incubation. In addition, after inducing differentiation, the UCNP nanoplatform that remained in the cytoplasm was used as a nanoprobe to monitor the MSCs in vitro and in vivo using the upconverted green/red light under the NIR light. Therefore, the UCNP nanoplatform displayed potential to be a powerful tool for the control of cell differentiation and the simultaneous long-term tracking of MSCs in vivo for regenerative medicine.
研究领域:
纳米技术
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干细胞生物学
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再生医学
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生物医学工程
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组织工程
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2021
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IF 9.028
Tingting Ku,Fang Hao,Xiaoxi Yang,Ziyu Rao,Qian S. Liu,Nan Sang,Francesco Faiola,Qunfang Zhou,Guibin Jiang
The tremendous potential for graphene quantum dots (GQDs) in biomedical applications has led to growing concerns of their health risks in human beings. However, present studies mainly focused on oxidative stress, apoptosis, and other general toxicity effects; the knowledge on the developmental toxicity and the related regulatory mechanisms is still far from sufficient. Our study revealed the development retardation of mouse embryonic stem cells (mESCs) caused by GQDs with a novel DNA methylation epigenetic mechanism. Specifically, GQDs were internalized into cells mainly via energy-dependent endocytosis, and a significant fraction of internalized GQDs remained in the cells even after a 48-h clearance period. Albeit with unobservable cytotoxicity or any influences on cell pluripotency, significant retardation was found in the in vitro differentiation of the mESCs into embryoid bodies (EBs) with the upregulation of Sox2 levels in GQD pretreatment groups. Importantly, this effect could be contributed by GQD-induced inhibition in CpG methylation of Sox2 through altering methyltransferase and demethyltransferase transcriptional expressions, and the demethyltransferase inhibitor, bobcat339 hydrochloride, reduced GQD-induced upregulation of Sox2. The current study first demonstrated that GQDs compromised the differentiation program of the mESCs, potentially causing development retardation. Exposure to this nanomaterial during gestation or early developmental period would cause adverse health risks and is worthy of more attention.
研究领域:
纳米技术
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干细胞生物学
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表观遗传学
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毒理学
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International Journal of Nanomedicine
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2026
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IF 8.7
Yunchao Wu,Xin Xu,Zhen Zhu,Fengyi Du,Guojun Zheng
Purpose Monotherapy with photothermal therapy (PTT) hardly achieves durable and significant antitumor efficacy. To further improve the therapeutic effect against tumors, in this study, the chemotherapeutic agent thioridazine (THZ) was loaded into a gel network formed by the Schiff base cross-linking of amino-functionalized graphene quantum dots (NH2-GQDs) and oxidized dextran. A pH-responsive injectable carbon dot composite hydrogel delivery system (NTD@Gel) with dual effects of photothermal therapy and chemotherapy was thereby constructed.Methods The techniques including HRTEM, XPS, FTIR, SEM and rheological tests were employed to verify the successful fabrication of NTD@Gel and characterize its physicochemical properties. In vitro and in vivo experiments were conducted to comprehensively evaluate the antitumor efficacy and biosafety of this hydrogel.Results NTD@Gel exhibited excellent photothermal conversion performance and biocompatibility, and enabled the rapid and sustained release of THZ in the acidic microenvironment. In vitro experiments confirmed that NTD@Gel could synergistically kill Hep1-6 hepatocellular carcinoma cells through photothermal ablation and THZ-induced oxidative damage, and inhibited the oncogenic Akt/Stat3 signaling pathway activation. In vivo experiments demonstrated that NTD@Gel combined with near-infrared laser irradiation significantly inhibited tumor growth, reduced CD133 and CD326 expression on tumor cells, effectively prolonged the survival time of tumor-bearing mice, and caused no obvious pathological damage in the major organs of mice.Conclusion NTD@Gel can significantly enhance the therapeutic efficacy against hepatocellular carcinoma and reduce the risk of metastasis and recurrence through the synergistic effect of photothermal therapy and chemotherapy.
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Theranostics
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2026
·Vol. 16
·期 2
·936
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IF 13.3
Menghui Liao,Xin Zhou,Hao Wei,Yanru Qi,Pan Feng,Xin Gao,Yangnan Hu,Yuyang Qiu,Yusong Wang,Hongbo Yang,Zhonghong Zhang,Zhongze Gu,Renjie Chai
Background: Contemporary cochlear implants (CIs) face unresolved dual challenges: biomechanical-electrochemical mismatch at the electrode-tissue interface and progressive spiral ganglion neuron (SGN) degeneration, severely limiting long-term auditory restoration. Integrating regenerative medicine with bioelectronic engineering offers promise to overcome these bottlenecks. Methods: A biohybrid neural interface was developed by embedding neural stem cells (NSCs) in photopolymerized poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/collagen hydrogel. Physicochemical properties were characterized via rheometry, electron microscopy, and electrochemical impedance spectroscopy. In vitro NSC responses (proliferation/differentiation) were quantified with EdU/Tuj1 assays. Therapeutic efficacy was evaluated in guinea pigs with ouabain-induced auditory neuropathy using auditory brainstem response (ABR) thresholds and immunohistochemical SGN quantification, comparing CI-alone versus NSC-hydrogel-CI groups. Results: The photopolymerized PEDOT:PSS/collagen hydrogel demonstrated cochlear tissue-matched viscoelastic properties (storage modulus: 8.7-12.4 kPa) with injectable sol-gel transition capability, while exhibiting enhanced bioelectronic coupling through high electrical conductivity (1.3 ± 0.1 S/m) and 97.7% reduction in charge transfer resistance. This electroactive microenvironment significantly promoted NSC proliferation (+51.6%) and neuronal differentiation (+76.4%) in vitro , effects further amplified by CI stimulation to achieve +71.5% proliferation and +23.4% neuronal differentiation. In vivo evaluation using ouabain-induced auditory neuropathy guinea pigs revealed substantial functional recovery, with ABR threshold improvements of 18.8-28.8 dB across 4-12 kHz frequencies by post-operative day 14, correlating with significant SGN regeneration in the apical turn (+11.14 cells/0.01 mm²), whereas CI-alone controls exhibited negligible recovery. Conclusions: This NSC-laden conductive hydrogel establishes a self-reinforcing therapeutic paradigm that simultaneously resolves electrode-tissue mismatch through optimized bioelectronic interfacing and reverses neurodegeneration via stem cell-mediated SGN regeneration. The dual-function platform pioneers active neural repair for next-generation neuroprosthetics.
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JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Beibei Hao,Haoping Wu,Siyi Zhang,Bin He
Research on the toxicity effects of nano-plastics on submerged macrophytes has been increasing over the past several years. However, how the endophytic bacteria of submerged macrophytes respond to nano-plastics remains unknown, although they have been widely shown to help terrestrial plants cope with various environmental stressors. Here, a microcosm experiment was performed to unravel the effects of high concentration of nano-plastics (20 mg/L) on three submerged macrophyte ( Vallisneria natans , Potamogeton maackianus , Myriophyllum spicatum ) and their endophytic bacterial communities. Results indicated that nano-plastics induced antioxidative stress in plants, but significantly reduction in relative growth rate (RGR) only occurred in V. natans (from 0.0034 to −0.0029 day -1 ), accompanied by change in the stem/leaves endophyte community composition. Further analysis suggested nano-plastics caused a reduction in environmental nutrient availability and the proportion of positive interactions between endophyte communities (43%), resulting in the lowest RGR of V. natans . In contrast, endophytes may help P. maackianus and M. spicatum cope with nano-plastic stress by increasing the proportion of positive correlations among communities (70% and 75%), leaving their RGR unaffected. Collectively, our study elucidates the species-specific response strategies of submerged macrophyte-endophyte to nano-plastics, which helps to reveal the different phytoremediation potential of submerged macrophytes against nano-plastic pollution.
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2023
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IF 5.1
Di Jia,Jiahui Han,Jimin Cai,Zhirong Huan,Yan Wang,Xin Ge
Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.
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Advanced Science
·
2023
·Vol. 10
·期 17
·2206814
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IF 15.1
Renwang Sheng,Jia Liu,Wei Zhang,Yifan Luo,Zhixuan Chen,Jiayu Chi,Qingyun Mo,Mingyue Wang,Yuzhi Sun,Chuanquan Liu,Yanan Zhang,Yue Zhu,Baian Kuang,Chunguang Yan,Haoyang Liu,Ludvig J. Backman,Jialin Chen
Stiffness is an important physical property of biomaterials that determines stem cell fate. Guiding stem cell differentiation via stiffness modulation has been considered in tissue engineering. However, the mechanism by which material stiffness regulates stem cell differentiation into the tendon lineage remains controversial. Increasing evidence demonstrates that immune cells interact with implanted biomaterials and regulate stem cell behaviors via paracrine signaling; however, the role of this mechanism in tendon differentiation is not clear. In this study, polydimethylsiloxane (PDMS) substrates with different stiffnesses are developed, and the tenogenic differentiation of mesenchymal stem cells (MSCs) exposed to different stiffnesses and macrophage paracrine signals is investigated. The results reveal that lower stiffnesses facilitates tenogenic differentiation of MSCs, while macrophage paracrine signals at these stiffnesses suppress the differentiation. When exposed to these two stimuli, MSCs still exhibit enhanced tendon differentiation, which is further elucidated by global proteomic analysis. Following subcutaneous implantation in rats for 2 weeks, soft biomaterial induces only low inflammation and promotes tendon-like tissue formation. In conclusion, the study demonstrates that soft, rather than stiff, material has a greater potential to guide tenogenic differentiation of stem cells, which provides comprehensive evidence for optimized bioactive scaffold design in tendon tissue engineering.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Shiqi Hao,Chen Tian,Yimeng Bai,Lihuang Wu,Lili Hao,Yi Kuang,Shengxiang Yang,Hongli Mao,Zhongwei Gu
Mesenchymal stem cells (MSCs) have gained increasing attention in various biomedical applications. However, conventional therapeutic approaches, such as direct intravenous injection, are associated with low cell survival due to the shear force during injection and the oxidative stress microenvironments in the lesion area. Herein, a photo-crosslinkable antioxidant hydrogel based on tyramine- and dopamine-modified hyaluronic acid (HA-Tyr/HA-DA) was developed. Meanwhile, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were encapsulated in HA-Tyr/HA-DA hydrogel using a microfluidic system to create size-controllable microgels ( [email protected] ). The HA-Tyr/HA-DA hydrogel was demonstrated to have good rheology, biocompatibility, and antioxidant properties for cell microencapsulation. The hUC-MSCs encapsulated in microgels showed a high viability and a significantly improved the survival rate under oxidative stress conditions. Therefore, the presented work provides a promising platform for MSCs microencapsulation, which may further improve the stem cell-based biomedical applications.
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Foods
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2023
·Vol. 12
·期 5
·1105
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IF 5.2
Hongdou Gao,Shixian Zeng,Xiaozhen Yue,Shuzhi Yuan,Jinhua Zuo,Qing Wang
The effect of palmitic acid (PA) on stem browning was investigated in freshly harvested mini-Chinese cabbage (Brassica pekinensis). Results indicated that concentrations of PA ranging from 0.03 g L−1to 0.05 g L−1inhibited stem browning and decreased the rate of respiration, electrolyte leakage, and weight loss, as well as the level of malondialdehyde (MDA) in freshly harvested mini-Chinese cabbage stored at 25 °C for 5 d. The PA treatment enhanced the activity of antioxidant enzymes (ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), 4-coumarate:CoA ligase (4CL) and phenylalamine ammonia lyase (PAL)), and inhibited the activity of polyphenol oxidase (PPO). The PA treatment also increased the level of several phenolics (chlorogenic acid, gallic acid, catechin, p-coumaric acid, ferulic acid, p-hydroxybenzoic acid, and cinnamic acid) and flavonoids (quercetin, luteolin, kaempferol, and isorhamnetin). In summary, results indicate that treatment of mini-Chinese cabbage with PA represents an effective method for delaying stem browning and maintaining the physiological quality of freshly harvested mini-Chinese cabbage due to the ability of PA to enhance antioxidant enzyme activity and the level of phenolics and flavonoids during 5 d.Keywords:mini-Chinese cabbage;palmitic acid;stem browning;antioxidant enzyme;phenolics;flavonoids
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International Journal of Nanomedicine
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2023
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IF 8
Xiaoling Wang,Jianqing Gao,Xumei Ouyang,Junbo Wang,Xiaoyi Sun,Yuanyuan Lv
Background Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.Purpose The objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.Methods Ptx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection.Results The optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone.Conclusion Based on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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IF 3.997
Jianfeng Li,Xiao Liu,Eva Tomaskovic-Crook,Jeremy M. Crook,Gordon G. Wallace
Graphene-based materials represent advanced platforms for tissue engineering and implantable medical devices. From a clinical standpoint, it is essential that these materials are produced using non-toxic and non-hazardous methods, and have predictable properties and reliable performance under variable physiological conditions; especially when used with a cellular component. Here we describe such a biomaterial, namely smart graphene-cellulose (G-C) paper, and its suitability for traditional planar two-dimensional (2D) or three-dimensional (3D) human cell support, verified by adipose-derived stem cell (ADSC) culture and osteogenic differentiation. G-C paper is prepared using commercially available cellulose tissue paper as a substrate that is coated by immersion-deposition with graphene oxide (GO) followed by reduction to reduced graphene oxide (RGO) without the use of toxic organic solvents. The fabrication process is amenable to large scale production and the resultant papers have low electrical resistivity (up to ∼300 Ω/sq). Importantly, G-C papers can be configured to 3D constructs by lamination with alginate and further modified by folding and rolling for 3D “origami-inspired” cell-laden structures.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
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IF 1.911
Qianqian Wei,Jiachang Jin,Xinyuan Wang,Qijun Shen,Mi Zhou,Shizhong Bu,Yabin Zhu
Polyurethane (PU) is a class of polymers that have been applied for tissue-engineering scaffolds. Cross-linked poly(ester urethane) (CPU), synthesized with ferric catalyst in our laboratory, was modified by silk fibroin (SF) grafting using our aminolysis and glutaradehyde crosslinking method. The physical and chemical properties of the materials were investigated by scanning electron microscope (SEM), atomic force microscope (AFM) and tensile tester. The results showed that SF grafted CPU possessed good strain and strength (4.29 ± 0.18 MPa/382.38 ± 0.71%). Its surface chemistry and roughness were fine to well support the growth of bone marrow mesenchymal stem cells (BMSC). The cells were verified to maintain the pluripotency after they were cultured in vitro for 2 weeks, which supplied us a good technology to keep cell’s stemness but proliferate cell’s number. These results are valuable for us to further study esophageal tissue engineering with BMSC and polyurethane materials as the components.
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危险品化学品经营许可证（带存储）