ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 10
·1807733
·
IF 15.621
Lin-Lin Bu,Lang Rao,Guang-Tao Yu,Lei Chen,Wei-Wei Deng,Jian-Feng Liu,Hao Wu,Qian-Fang Meng,Shi-Shang Guo,Xing-Zhong Zhao,Wen-Feng Zhang,Guojun Chen,Zhen Gu,Wei Liu,Zhi-Jun Sun
Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane-coated iron oxide magnetic nanoparticle (MN) {[CSC-P]MN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of “don't eat me” signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The [CSC-P]MNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, [CSC-P]MNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the [CSC-P]MNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane-coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment.
研究领域:
肿瘤学
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纳米医学
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生物材料学
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JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Yu Gaoxiang,Ding Jian,Yang Ningning,Ge Lu,Chen Nuo,Zhang Xuzi,Wang Qiuchen,Liu Xian,Zhang Xuanlong,Jiang Xiaoqiong,Geng Yibo,Zhang Chenxi,Pan Jiadong,Wang Xiangyang,Gao Weiyang,Li Zhijie,Zhang Hongyu,Ni Wenfei,Xiao Jian,Zhou Kailiang,Yang Liangliang
In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.
研究领域:
组织工程
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再生医学
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细胞生物学
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分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Jiaqi Chen,Jiayue Zhao,Yibin Xu,Xianglin Fei,Shujie Xu,Binke Chen,Wenzi Wu,Jiachen Zhuang,Xiuan Zhan,Aikun Fu
Enteric Lactobacillus plays a crucial role in maintaining the intestinal barrier integrity. Lactobacillus reuteri , one of the most described probiotic species of Lactobacillus , has been shown to alleviate enteritis-associated intestinal mucosal damage by stimulating the expansion of intestinal stem cells (ISCs). However, the underlying ligand-protein interactions remain unexplored. Therefore, this study aimed to elucidate the specific molecular mechanisms by which L. reuteri and its metabolites govern ISC stemness. We employed broiler enteritis model and organoid culture to compare the probiotic effect of a wild-type (WT) L. reuteri strain and a reuterin-deficient isogenic mutant. Compared to the WT strain, the deficient strain exhibited an impaired ability to alleviate inflammation, restore the intestinal barrier, and stimulate ISC proliferation both in vivo and ex vivo, indicating that reuterin is the essential effector. Furthermore, bioorthogonal click chemistry combined with in silico molecular docking were utilized to map the direct host protein targets. We identified protein disulfide-isomerase 1 (PDIA1), an endoplasmic reticulum (ER)-resident redox-active protein, as the direct binding partner of reuterin, characterized by a strong binding affinity. The inactivation of PDIA1 by reuterin binding increased ER-derived reactive oxygen species (ROS) level, leading to the upregulation of Wnt/β-catenin pathway and the maintenance of ISCs. In conclusion, by inactivating the ER-resident PDIA1, L. reuteri -derived reuterin promoted ISC proliferation and ameliorated intestinal mucosal damage.
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高影响因子
Advanced Science
·
2022
·Vol. 10
·期 4
·2204786
·
IF 17.521
Penghong Chen,Shijie Tang,Ming Li,Dezhi Wang,Caixiang Chen,Yiqun Qiu,Zhuoqun Fang,Haoruo Zhang,Hangqi Gao,Haiyan Weng,Kailun Hu,Jian Lin,Qingxia Lin,Yi Tan,Shirong Li,Jinghua Chen,Liangwan Chen,Xiaosong Chen
The highly heterogeneous characteristics of Wharton's jelly mesenchymal stem cells (WJ-MSCs) may be responsible for the poor clinical outcomes and poor reproducibility of treatments based on WJ-MSCs. Exploration of WJ-MSC heterogeneity with multimodal single-cell technologies will aid in establishing accurate MSC subtyping and developing screening protocols for dominant functional subpopulations. Here, the characteristics of WJ-MSCs are systematically analyzed by single cell and spatial transcriptome sequencing. Single-cell transcriptomics analysis identifies four WJ-MSC subpopulations, namely proliferative_MSCs, niche-supporting_MSCs, metabolism-related_MSCs and biofunctional-type_MSCs. Furthermore, the transcriptome, cellular heterogeneity, and cell-state trajectories of these subpopulations are characterized. Intriguingly, the biofunctional-type MSCs (marked by S100A9, CD29, and CD142) selected in this study exhibit promising wound repair properties in vitro and in vivo. Finally, by integrating omics data, it has been found that the S100A9 + CD29 + CD142 + subpopulation is more enriched in the fetal segment of the umbilical cord, suggesting that this subpopulation deriving from the fetal segment may have potential for developing into an ideal therapeutic agent for wound healing. Overall, the presented study comprehensively maps the heterogeneity of WJ-MSCs and provides an essential resource for future development of WJ-MSC-based drugs.
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TISSUE & CELL
·
2023
·
IF 2.6
Lei Huang,Mengxuan Bian,Shunyi Lu,Jiayi Wang,Jieqin Yu,Libo Jiang,Jian Zhang
Ferroptosis is a novel form of cell death, which is a unique modality of cell death and closely associated with iron concentrations, generation of reactive oxygen species (ROS), and accumulation of the lipid reactive oxygen species. In the present study, the anti-ferroptosis effects of Engeletin was studied in erastin-induced bone marrow mesenchymal stem cells (BMSCs). After treatment with Engeletin, cell viability was determined by CCK-8 assay. The production of ROS, malonaldehyde (MDA), Superoxide dismutase (SOD) activities and glutathione peroxidase (GSH) were detected by using commercially-available kits. Ferroptosis-related proteins (GPX4, SLC7A11, TFR1, FPN1, Nrf2, Keap1) were evaluated by Western blotting. Osteogenic capacity was evaluated by ALP staining and ARS staining. The expression of osteogenic-related proteins (OPN, Runx2, OCN) were evaluated by Western blotting and changes in mRNA (ALP, BMP-2, COL-1, Osterix) were evaluated by RT-PCR. Consistent improvements in angiogenesis are observed with Engeletin in the presence of erastin. Engeletin significantly alleviated erastin-induced oxidative damage and protected against ferroptosis in BMSCs. Ferroptosis was inhibited by Engeletin, leading to decreasing reducing accumulation of ROS and lipid peroxidation products. Moreover, Engeletin promoted osteogenic differentiation in BMSCs and angiogenesis in human umbilical vein endothelial cells (HUVECs). Taken together, these findings indicate that Engeletin can protect BMSCs from erastin-induced ferroptosis through the Nrf2/Keap1 antioxidant pathway and identify Engeletin as a novel ferroptosis inhibitor, suggesting that Engeletin may promote resistance to ferroptosis and enable osteogenic function of BMSCs.
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ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Lilan Xu,Jiafu Mu,Zhiyuan Ma,Peihua Lin,Fan Xia,Xi Hu,Jiahe Wu,Jian Cao,Shanbiao Liu,Tianchen Huang,Daishun Ling,Jianqing Gao,Fangyuan Li
Mesenchymal stem cell (MSC)-based therapy has emerged as a promising strategy for the treatment of spinal cord injury (SCI). However, the hostile microenvironment of SCI, which can adversely affect the survival and paracrine effect of the implanted MSCs, severely limits the therapeutic efficacy of this approach. Here, we report on a ceria nanozyme-integrated thermoresponsive in situ forming hydrogel (CeNZ-gel) that can enable dual enhancement of MSC viability and paracrine effect, leading to highly efficient spinal cord repair. The sol–gel transition property of the CeNZ-gel at body temperature ensures uniform coverage of the hydrogel in injured spinal cord tissues. Our results demonstrate that the CeNZ-gel significantly increases the viability of transplanted MSCs in the microenvironment by attenuating oxidative stress and, more importantly, promotes the secretion of angiogenic factors from MSCs by inducing autophagy of MSCs. The synergy between the oxidative stress-relieving effect of CeNZs and the paracrine effect of MSCs accelerates angiogenesis, nerve repair, and motor function recovery after SCI, providing an efficient strategy for MSC-based SCI therapy.
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Advanced Biology
·
2023
·
IF 3.7
Xinyue Wang,Liuxu Sun,Xuan Qin,Jiayi You,Jing Zhang,Yang Xia
Cell-free therapy using conditioned medium (CM) from mesenchymal stem cells takes full advantage of the bioactive factors secreted by the cells while avoiding disadvantages such as immune rejection and tumor formation due to cell transplantation. In this study, human periodontal ligament stem cells (PDLSCs) are modified with the superparamagnetic iron oxide nanoparticle (SPION)-based nanodrug ferumoxytol (PDLSC-SPION). Compared with PDLSCs, PDLSC-SPION showed good cell viability and better osteogenic differentiation ability. Cell-free CM is collected and the anti-inflammatory capacity of PDLSC CM and PDLSC-SPION CM is assessed by treatment of lipopolysaccharide-stimulated macrophages and IL-17-stimulated human gingival fibroblasts. Both CMs inhibited the expression of proinflammatory cytokines in cells, and the therapeutic effect is more distinct for PDLSC-SPION CM than PDLSC CM, which may be due to their different proteomic compositions. Therefore, modification of PDLSCs with ferumoxytol enhances the anti-inflammatory capacity of its CM, making it more potentially useful for the treatment of inflammatory diseases such as periodontitis.
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高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2022
·
IF 10.319
Xuewei Zhang,Bixue Wang,Hua Hong,Ying Wang,Jiashang Liu,Changsheng Liu,Xi Chen
Damaged neurons and harsh microenvironments contribute to the injury cascades following traumatic brain injury (TBI). Mesenchymal stem cell (MSC) therapy is considered a viable choice for brain injury treatment; however, its clinical use is hindered by limited engraftment, low survival ratio, and uncontrolled differentiation. Herein, the decellularized brain extracellular matrix (dBECM) was prepared through a new method as a delivery system for MSCs. dBECM-based hydrogel with favorable biochemical and biomechanical features provides a microenvironment for MSCs in nerve repair. The MSCs-encapsulated dBECM-based hydrogel is shown to improve neuron compensation and structural regeneration, alleviate neuroinflammation, and promote M1-to-M2 polarization of microglia. Our results first demonstrate that the combination of dBECM and MSCs is a critical vehicle to promote TBI repair from neurogenesis and immunoregulation, showing promise for the physiological recovery of neurogenic diseases and injuries.
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Advanced Healthcare Materials
·
2022
·Vol. 12
·期 3
·2201925
·
IF 11.092
Xianpeng Huang,Di Chen,Chengzhen Liang,Kesi Shi,Xiaopeng Zhou,Yuang Zhang,Yi Li,Jiangjie Chen,Kaishun Xia,Jiawei Shu,Biao Yang,Jingkai Wang,Haibin Xu,Chao Yu,Feng Cheng,Shaoke Wang,Yongxiang Zhang,Chenggui Wang,Liwei Ying,Hao Li,Meiling Han,Fangcai Li,Yiqing Tao,Qian Zhao,Qixin Chen
Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide- co -acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.
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BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Mohsen Sheykhhasan,Razieh Amini,Sara Soleimani Asl,Massoud Saidijam,Seyed Mahmoud Hashemi,Rezvan Najafi
Alzheimer's disease (AD) is a degenerative disease that causes memory and learning impairments as well as dementia. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with AD. This study investigated the effects of drug delivery of COQ10 by exosomes derived from adipose-derived stem cells (ADSCs-Exo) on cognition, memory, and neuronal proliferation in a rat model of Streptozotocin (STZ)-induced AD. Since the establishment of the AD model, the rats have received intraperitoneal injections of CoQ10, Exo, or CoQ10-loaded ADSCs-Exo (Exo+ CoQ10). The passive avoidance test and the Morris water maze (MWM) were used to assess memory and cognition changes. Cell density was determined using histological methods. The expression of BDNF was measured using an ELISA kit. SOX2 expression was determined using immunohistochemistry. According to the results of the MWM and passive avoidance task, Exo+CoQ10 significantly improved STZ-induced memory impairment compared to CoQ10 and Exo groups alone. Furthermore, BDNF expression increased in the STZ-induced rats after Exo+ CoQ10, when compared to the CoQ10 and Exo groups. In addition, Exo+CoQ10 had the highest cell density and SOX2 gene expression, when compared to the CoQ10 and Exo groups. According to the findings of this study, Exo+ COQ10 enhanced cognition and memory deficiency in Alzheimer's disease by boosting BDNF and SOX2 levels in the hippocampus. Hence, the use of exosomes derived from adipose-derived stem cells as the carrier of CoQ10 may increase the therapeutic effect of CoQ10, which can possibly be due to the regenerative properties of the exosomes.
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Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xiao Shuwei,Wang Pengchao,Zhao Jian,Ling Zhengyun,An Ziyan,Fu Zhouyang,Fu Weijun,Zhou Jin,Zhang Xu
The bladder patch constructed with the bladder acellular matrix (BAM) and adipose-derived stem cells (ASCs) was incubated with the omentum for bladder reconstruction in a rat model of bladder augmentation cystoplasty. A self-designed perfusion system and five different decellularization protocols were used to prepare the BAM. Finally, an optimal protocol (group C) was screened out by comparing the cell nucleus residue, collagen structure preservation and biologically active components retention of the prepared BAM. ASCs-seeded (BAM-ASCs group) and unseeded BAM (BAM group) were incubated with the omentum for 7 days to promote neovascularization and then perform bladder reconstruction. Hematoxylin and eosin and Masson’s trichrome staining indicated that the bladder patches in the BAM-ASCs group could better regenerate the bladder wall structure compared to the BAM group. Moreover, immunofluorescence analyses demonstrated that the ASCs could promote the regeneration of smooth muscle, neurons and blood vessels, and the physiological function (maximal bladder capacity, max pressure prior to voiding and bladder compliance) restoration in the BAM-ASCs group. The results demonstrated that the self-designed perfusion system could quickly and efficiently prepare the whole bladder scaffold and confirmed that the prepared BAM could be used as the scaffold material for functional bladder tissue engineering applications.
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高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Zhou Mengyang,Guo Min,Shi Xincui,Ma Jie,Wang Shutao,Wu Shuo,Yan Weiqun,Wu Feng,Zhang Peibiao
Multifunctionality has becoming essential for bone tissue engineering materials, such as drug release. In this study, icariin (ICA)-incorporated poly(glycolide-co-caprolactone) (PGCL) porous microcarriers were fabricated and then coated with decellularized extracellular matrix (dECM) which was derived from bone marrow mesenchymal stem cells (BMSC). The porous structure was generated due to the soluble gelatin within the microcarriers. The initial released ICA in microcarriers regulated osteogenic ECM production by BMSCs during ECM formation. The dECM could further synergistically enhance the migration and osteogenic differentiation of BMSCs together with ICA as indicated by the transwell migration assay, ALP and ARS staining, as well as gene and protein expression. Furthermore, in vivo results also showed that dECM and ICA exhibited excellent synergistic effects in repairing rat calvarial defects. These findings suggest that the porous microcarriers loaded with ICA and dECM coatings have great potential in the field of bone tissue engineering.
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