COMPOSITES PART B-ENGINEERING
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2023
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IF 13.1
Yang Liu,Wen Zhang,Cheng Hu,Cheng Zheng,Fanjun Zhang,Li Yang,Zhengyong Li,Yunbing Wang
Stem cell transplantation can replace lost and damaged neurons after ischemic stroke and has been proposed as a potential treatment for stroke. However, stem cell therapy is challenged by poor cell retention, survival, and differentiation following transplantation. In this study, we developed a composite hydrogel incorporating brain decellularized extracellular matrix (dECM) and a matrix metallopeptidase (MMP)-responsive host–guest (HG) hydrogel that acts as a platform for human induced pluripotent stem cell-derived neural stem cells (iPSC-NSCs) delivery to improve transplant stem cell survival and differentiation. The optimized composite hydrogel ratio was screened by rheology analysis and neurite outgrowth assessment. We then examined the effects of HG/dECM composite hydrogels on iPSC-NSCs survival and differentiation on two-dimensional surfaces modified with hydrogel and in a three-dimensional hydrogel network. Moreover, iPSC-NSCs-laden composite hydrogels were injected into the infarct cavity in an ischemic stroke model to replace lost and damaged nerve cells. As expected, the HG/dECM composite hydrogels better facilitated the survival and differentiation of iPSC-NSC in vivo than the control. Likewise, the iPSC-NSCs loaded in HG/dECM composite hydrogels showed superior retention and survival in the cortical infarct cavity, and the composite hydrogels promoted the differentiation of iPSC-NSCs into neurons. Overall, HG/dECM composite hydrogels are a promising platform to regulate stem cell survival and differentiation.
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International Journal of Nanomedicine
·
2023
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IF 8
Zhan Su,Duanqin Liu,Liying Chen,Jun Zhang,Lu Ru,Zhiyu Chen,Zhennan Gao,Xuxia Wang
Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment.Methods We explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice.Results The CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid.Conclusion These results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.
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CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2019
·Vol. 35
·期 3
·514-520
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IF 1.071
Liu Guomin,Li Yalong,Yang Shuting,Zhao Yi’an,Lu Tiancheng,Jia Wenyuan,Ji Xuan,Luo Yungang
To explore the ability of dihydroxyphenylalanine-insulin-like growth factor-1(DOPA-IGF-1) coated hydroxyapatite/poly(lactic-co-glycolic acid)(HA/PLGA) microspheres to promote the proliferation and osteoclastic differentiation of rabbit bone mesenchymal stem cells(rBMSCs), HA/PLGA microspheres with different HA content (10%, 30%, 50%, mass fraction) were prepared by electrospinning method and HA/PLGA microspheres with 50% HA were coated with IGF-1 and DOPA-IGF-1, respectively. They were co-cultured with rBMSCs, respctively. Cell counting kit-8(CCK-8) detection, confocal laser scanning microscopy(CLSM), alkaline phosphatase(ALP) detection and osteogenesis related genes COL1A1 , Runx2 and bone morphogenetic protein-2( BMP-2 ) detection were conducted to detect the proliferation activity, cell morphology, differentiation ability and the expression level of osteogenesis-related genes of cells cultured on all microspheres groups. The results showed that rBMSCs proliferation increased in an HA content dependent manner, and cells proliferated more in the IGF-1 coated and DOPA-IGF-1 coated groups, in particular in DOPA-IGF-1 coated group, and the differences were more remarkable over time ( P <0.05). HA/PLGA microspheres promoted the proliferation and osteogenic differentiation of rBMSCs, and DOPA-IGF-1 coating enhanced the proliferation and osteogenic differentiation of rBMSCs.
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Cell Death & Disease
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2018
·Vol. 9
·期 3
·1-15
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IF 5.638
Ding Yue,Liang Xiaoting,Zhang Yuelin,Yi Li,Shum Ho Cheung,Chen Qiulan,Chan Barbara P.,Fan Huimin,Liu Zhongmin,Tergaonkar Vinay,Qi Zhongquan,Tse Hung-fat,Lian Qizhou
Immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. Our previous studies showed that activation of nuclear factor-kappa B (NF-κB) regulates cytokine/growth factor secretion by MSCs. This study aimed to elucidate the role of Rap1 (repressor/activator protein), a novel modulator involved in the NF-κB pathway, in regulating the immunomodulatory potency of MSCs in acute allograft rejection of heart transplantation. The immunosuppressive potency of wild-type MSCs (WT-MSCs) or Rap1-deficient MSCs (Rap1 −/− -MSCs) was examined in mice with acute allograft rejection following heart transplantation. With a combination of immunosuppressant rapamycin at a dose of 1 mg/kg/d, WT-MSCs notably prolonged the survival of the transplanted heart compared with Rap1 −/− -MSCs. Rap1 −/− -MSCs displayed a marked insensitivity to inhibit the mixed lymphocyte reaction (MLR) due to impaired cytokine production and a significantly reduced activity of NF-κB signaling in vitro . Finally, transplantation of encapsulated WT-MSCs greatly prolonged the survival of the heart allograft compared with encapsulated Rap1 −/− -MSCs. Our results indicate that Rap1 is essential to maintain the immunomodulatory function of MSCs. Deletion of Rap1 results in impaired immunomodulatory function of MSCs.
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2019
·Vol. 26
·期 26
·26947-26962
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IF 2.914
Zhou Nan,Zu Junning,Feng Qiuju,Chen Huanli,Li Juan,Zhong Mei-e,Zhou Zhi,Zhuang Shuxin
To clarify the adsorption mechanism of multi-ions on biochars in competitive environment is very important for the decontamination of co-existed heavy metals. Herein, tobacco stem was pyrolyzed in different temperatures with selected residences to obtain biochars with various surface chemistry. Then the adsorption of co-existed typical heavy-metal ions like lead, cadmium, and copper was studied, followed with systematic analysis of surface properties of the post-adsorption biochars. After carefully examining the adsorption performance and surface property alteration of the demineralized biochars, the adsorption mechanism of multi-ions in competitive environment was discovered. Lead showed the most competitive nature with co-existence of cadmium and copper, but the adsorption capacity reduced significantly with the removal of minerals. Combined with the observation of large amount of lead containing crystals on the post-adsorption biochars, the main adsorption mechanism of lead should be precipitation. The adsorb capability of copper barely changed for biochars with and without minerals, which suggests the best affinity of copper on surface functional groups even with large content of competitors. Biochar that pyrolyzed in 700 °C for 6 h that contained more aromatic structures showed the highest sorbing capability of cadmium, which suggested the dominant position of cation-π interaction in cadmium removal.
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Scientific Reports
·
2017
·Vol. 7
·期 1
·1-14
·
IF 4.259
Huang Zebin,Xu Jiankun,Chen Jiebin,Chen Hongjiang,Wang Hailong,Huang Zhonglian,Chen Youbin,Lu Xiaolin,Lu Fushen,Hu Jun
The aim of this study was to evaluate the direct photoacoustic (PA) effect on bone marrow mesenchymal stem cells (BMSCs) which is a key cell source for osteogenesis. As scaffold is also an indispensable element for tissue regeneration, here we firstly fabricated a composited sheet using polylactic-co-glycolic acid (PLGA) mixing with graphene oxide (GO). BMSCs were seeded on the PLGA-GO sheets and received PA treatment in vitro for 3, 9 and 15 days, respectively. Then the BMSCs were harvested and subjected to assess alkaline phosphatase (ALP) activity, calcium content and osteopontin (OPN) on 3, 9 and 15 days. For in vivo study, PLGA-GO sheet seeded with BMSCs after in vitro PA stimulation for 9 days were implanted to repair the bone defect established in the femoral mid-shaft of Sprague-Dawley rat. PLGA-GO group with PA pretreatment showed promising outcomes in terms of the expression of ALP, OPN, and calcium content, thus enhanced the repair of bone defect. In conclusion, we have developed an alternative approach to enhance the repair of bone defect by making good use of the beneficial effect of PA.
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Liuxin Yang,Fengya Jing,Dandan Wei,Xiaocong Zhao,Yinghua Tao,Tao Liu,Tianzhu Zhang
Abdominal wall defects caused by trauma, congenital rupture, and intra-abdominal infection remain challenging due to the large wound area and complex complications. Herein, an assembled mesenchymal stem cell (MSCs)-laden granular hydrogel (termed assembled GSD@FPs), loaded with basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), is developed. This hydrogel is constructed through dynamic covalent cross-linking ( via borate ester bonds) among dopamine-grafted gelatin methacrylamide (GelMA-DA), phenylborate-modified hyaluronic acid (HA-PBA), and epigallocatechin-3-gallate (EGCG), serving as multifunctional bulk building blocks for cell delivery and abdominal wall repair. The designed assembled granular hydrogels possess good rheological properties, self-healing, injectability, and tissue-adhesion properties. Detailed in vitro cell experiments are conducted, revealing that the GSD@FPs granular hydrogels can effectively promote cell proliferation, cell migration and angiogenesis. Furthermore, in abdominal wall defects, assembled GSD@FPs significantly accelerates the tissue healing process by simultaneously inhibiting the inflammatory response, promoting collagen deposition, and promoting cell proliferation and angiogenesis. Importantly, the assembled GSD@FPs granular hydrogels can also provide mechanical support and increase the thickness of regenerated tissue (1727.8 ± 169.6 μm for the control group, 3204.2 ± 278.5 μm for the assembled GSD@FPs group at 14 d). Eventually, the GSD granular hydrogels biodegraded, facilitating tissue remodeling and generating new muscle tissues. Therefore, this study provides a promising strategy with great potential for application in abdominal wall repair.
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BIOMATERIALS
·
2024
·
IF 12.8
Chen Xiao,Xing Wang,Shiyou Li,Zhijie Zhang,Jiayuan Li,Qingyuan Deng,Xiang Chen,Xiangliang Yang,Zifu Li
Cuproptosis is a new kind of cell death that depends on delivering copper ions into mitochondria to trigger the aggradation of tricarboxylic acid (TCA) cycle proteins and has been observed in various cancer cells. However, whether cuproptosis occurs in cancer stem cells (CSCs) is unexplored thus far, and CSCs often reside in a hypoxic tumor microenvironment (TME) of triple negative breast cancers (TNBC), which suppresses the expression of the cuproptosis protein FDX1, thereby diminishing anticancer efficacy of cuproptosis. Herein, a ROS-responsive active targeting cuproptosis-based nanomedicine CuET@PHF is developed by stabilizing copper ionophores CuET nanocrystals with polydopamine and hydroxyethyl starch to eradicate CSCs. By taking advantage of the photothermal effects of CuET@PHF, tumor hypoxia is overcome via tumor mechanics normalization, thereby leading to enhanced cuproptosis and immunogenic cell death in 4T1 CSCs. As a result, the integration of CuET@PHF and mild photothermal therapy not only significantly suppresses tumor growth but also effectively inhibits tumor recurrence and distant metastasis by eliminating CSCs and augmenting antitumor immune responses. This study presents the first evidence of cuproptosis in CSCs, reveals that disrupting hypoxia augments cuproptosis cancer therapy, and establishes a paradigm for potent cancer therapy by simultaneously eliminating CSCs and boosting antitumor immunity.
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Discover Oncology
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2024
·Vol. 15
·期 1
·1-15
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IF 2.8
Li Weinan,Fu Yuhan,Sun Jialin,Gong Hexin,Yan Ru,Wang Yanhong
Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (β-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer.
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Oncotarget
·
2016
·
IF 5.008
Tingting Meng,Jingwen Liu,Lijuan Wen,Ming Yuan,Bolin Cheng,Yingwen Hu,Yun Zhu,Xuan Liu,Hong Yuan,Fuqiang Hu
Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro , on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo , the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What's more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research.
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Scientific Reports
·
2016
·
IF 5.228
Zhe Chen,Qing Luo,Chuanchuan Lin,Dongdong Kuang,Guanbin Song
Microgravity induces observed bone loss in space flight, and reduced osteogenesis of bone mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning of the actin cytoskeleton induced by microgravity may cause the inhibited osteogenesis of BMSCs, but the underlying mechanism remains obscure. In this study, we demonstrated that actin cytoskeletal changes regulate nuclear aggregation of the transcriptional coactivator with PDZ-binding motif (TAZ), which is indispensable for osteogenesis of bone mesenchymal stem cells (BMSCs). Moreover, we utilized a clinostat to model simulated microgravity (SMG) and demonstrated that SMG obviously depolymerized F-actin and hindered TAZ nuclear translocation. Interestingly, stabilizing the actin cytoskeleton induced by Jasplakinolide (Jasp) significantly rescued TAZ nuclear translocation and recovered the osteogenic differentiation of BMSCs in SMG, independently of large tumor suppressor 1(LATS1, an upstream kinase of TAZ). Furthermore, lysophosphatidic acid (LPA) also significantly recovered the osteogenic differentiation of BMSCs in SMG through the F-actin-TAZ pathway. Taken together, we propose that the depolymerized actin cytoskeleton inhibits osteogenic differentiation of BMSCs through impeding nuclear aggregation of TAZ, which provides a novel connection between F-actin cytoskeleton and osteogenesis of BMSCs and has important implications in bone loss caused by microgravity.
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International Journal of Nanomedicine
·
2016
·
IF 4.32
Xinxin Yan,Wen Yang,Zengwu Shao,Shuhua Yang,Xianzhe Liu
Carbon nanomaterials are becoming increasingly significant in biomedical fields since they exhibit exceptional physicochemical and biocompatible properties. Today, the stem cells offer potentially new therapeutic approaches in tissue engineering and regenerative medicine. However, the induction of differentiation into specific lineages remains challenging, which provoked us to explore the biomedical applications of carbon nanomaterials in stem cells. In this study, we investigated the interactions between graphene/single-walled carbon nanotube (G/SWCNT) hybrids and rat mesenchymal stem cells (rMSCs) and focused on the proliferation and differentiation of rMSCs treated with G/SWCNT hybrids. Cell viability and morphology were evaluated using cell counting kit-8 assay and immunofluorescence staining, respectively. Osteogenic differentiation evaluated by alkaline phosphatase activity of MSCs proved to be higher after treatment with G/SWCNT hybrids, and the mineralized matrix nodule formation was also enhanced. In addition, the expression levels of osteogenic-associated genes were upregulated, while the adipocyte-specific markers were downregulated. Consistent with these results, we illustrated that the effect of G/SWCNT hybrids on the process of osteogenic differentiation of rMSCs can be modulated by activating the p38 signaling pathway and inhibiting the extracellular signal-regulated kinase 1/2 pathway. Nevertheless, our study suggests that carbon nanomaterials offer a promising platform for regenerative medicine in the near future.
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