Nanoscale
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2018
·Vol. 10
·期 27
·13106-13121
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IF 7.233
Zhaojie Wang,Peng Liang,Xiaolie He,Bin Wu,Qiang Liu,Ziping Xu,Huijun Wu,Zhongmin Liu,Yechang Qian,Shilong Wang,Rongrong Zhu
Glioblastoma (GBM) is the most malignant and lethal glioma in human brain tumors and contains self-renewing, tumorigenic glioma stem cells (GSCs) that contribute to tumor initiation, therapeutic resistance and further recurrence. In this study, we combined in vitro cellular efficacy with in vivo antitumor performance to evaluate the outcome of an etoposide (VP16) loaded layered double hydroxide (LDH) nanocomposite (L-V) on human GSCs. The effects on GSC proliferation and apoptosis showed that loading with LDH could significantly sensitize GSCs to VP16 and enhance the GSC elimination. Further qPCR and western blot assays demonstrated that L-V could effectively attenuate GSC related pluripotency gene expression and reduce the cancer stemness. An in vivo GSC xenograft mice model showed that L-V can overcome drug resistance, eradicate GSCs, sharply decrease the stemness and reverse the epithelial–mesenchymal transition (EMT). RNA-seq analysis elucidated that L-V plays a vital role by down-regulating the PI3K/AKt/mTOR expression and activating the Wnt/GSK3β/β-catenin signaling pathway, hence leading to GSC stemness loss and greatly enhancing the GSC targeting effect. Taken together, this study demonstrated the outstanding performance of L-V reversing the drug resistance of GSCs, thus providing a novel strategy for clinical translation application of nanomedicine in malignant glioma chemotherapy.
研究领域:
肿瘤学
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纳米技术
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药学
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癌症生物学
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神经科学
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高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 13
·2673-2688
·
IF 5.344
Huanhuan Yan,Yu Wang,Linlong Li,Xiaosong Zhou,Xincui Shi,Yen Wei,Peibiao Zhang
An effective treatment for spinal cord injury (SCI) remains a severe clinical challenge due to the intrinsically limited regenerative capacity and complex anatomical structure of the spinal cord. The combination of biomaterials, which serve as scaffolds for axonal growth, cells and neurotrophic factors, is an excellent candidate for spinal cord regeneration. Herein, a new micropatterned conductive electrospun nanofiber mesh was constructed with poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]}/PCL (PCAT) using a rotation electrospinning technology. The aim was to study the synergistic effects of electrical stimulation (ES) and a micropatterned conductive electrospun nanofiber mesh incorporated with nerve growth factor (NGF) on the differentiation of rat nerve stem cells (NSCs). The hydrophilicity of the conductive nanofiber mesh could be tailored by changing the dopamine (DA) and aniline tetramer (AT) content from 19° to 79°. A favorable electroactivity and conductivity was achieved by the AT segment of PCAT. The as-fabricated micropatterned electrospun nanofiber mesh possessed a regularly aligned valley and ridge structure, and the diameter of the nanofiber was 312 ± 58 nm, while the width of the valley and ridge was measured to be 210 ± 17 μm and 200 ± 16 μm, respectively. The growth and neurite outgrowth of differentiated NSCs were observed along the valley of the micropatterned nanofiber mesh. In addition, the NGF loaded micropatterned conductive electrospun nanofiber mesh combined with ES exhibited the highest cell viability, and effectively facilitated the differentiation of NSCs into neurons and suppressed the formation of astrocytes, thus exhibiting a great application potential for nerve tissue engineering.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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Applied Materials Today
·
2021
·
IF 10.041
Zhijun Lin,Bolong Liu,Haixia Wang,Hailun Zhan,Yong Huang,Jianxi Lu,Yu Tao,Mingqiang Li,Xiangfu Zhou
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a critical disease characterized by debilitating pelvic pain associated with lower urinary tract symptoms. Effective therapeutic strategies remain challenging due to their elusive pathogenesis. Mesenchymal stem cell (MSC) therapy offers a promising therapeutic approach for IC/BPS treatment. Yet, the ethical arguments and tumorigenic risks from cell therapy by stem cells restrict the clinical application. Herein, we developed a nanoparticle that encapsulates the conditioned medium (CM) from stem cells and coated with cationic N-trimethyl chitosan chloride (TMC) on the surface to improve the penetration of epithelial barrier in intravesical therapy for IC/BPS. The TMC coating enhanced the accumulation of CM-loaded nanoparticles in the urothelium and subsequently improved the therapeutic efficacy on the mechanical threshold and micturition function through facilitating the effect of anti-inflammation and BDNF/TrkB signaling, which provides a great potential application on the transmucosal delivery platform for intravesical therapy of IC/BPS.
研究领域:
药学
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干细胞生物学
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泌尿学
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DOI
高影响因子
Materials Today Communications
·
2026
·
IF 4.9
Jia Ning,Zhen Wang,Xin Zhang,Changyi Li,Zhimin Zhou
Periodontitis is a chronic inflammatory disease that progressively destroys periodontal tissues and alveolar bone, posing a significant challenge for clinical regeneration. Tissue engineering strategies integrating stem cells, biomaterials, and bioactive agents hold promise for overcoming the limitations of current periodontal regenerative approaches. In this study, we developed an injectable PLGA composite microscaffold-based co-delivery system with a porous architecture for the combined delivery of icariin (ICA) and bone marrow-derived mesenchymal stem cells (BMSCs). ICA-loaded PLGA composite microscaffolds (ICA-PLGA) were fabricated by a double emulsion–solvent evaporation method, followed by fibrinogen (Fg) surface modification via electrostatic layer-by-layer assembly to generate ICA-PLGA-Fg microscaffolds with improved cell-adhesive properties. These porous microscaffolds exhibited sustained ICA release for up to 28 days and enhanced BMSC adhesion and spreading. In vitro, ICA-PLGA-Fg supported favorable cytocompatibility and enhanced osteogenic differentiation of BMSCs under inflammatory conditions. In vivo, BMSC-seeded ICA-PLGA-Fg constructs implanted into rat periodontitis-related alveolar bone defects achieved markedly greater bone regeneration compared with both periodontitis and PLGA-only controls. Collectively, this co-delivery platform integrates sustained ICA release with a bioactive, cell-supportive microscaffold interface, promotes osteogenic responses in vitro, and shows therapeutic promise for enhancing periodontal bone repair in vivo.
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高影响因子
Stem Cell Research & Therapy
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2026
·Vol. 17
·期 1
·200
·
IF 7.8
Chen Qi,Chen Xiaolong,Yang Qu,Miao Xinxin,Yuan Jinghong,Ding Shuihua,Ding Rui,Cai Shenghao,Li Bin,Cheng Xigao
Background Intervertebral disc degeneration (IVDD) is characterized by progressive nucleus pulposus cell loss and extracellular matrix degradation, in which persistent oxidative stress plays a critical pathogenic role. Transplantation of nucleus pulposus–derived stem cells (NPSCs) is a promising therapeutic strategy, yet the hostile oxidative microenvironment severely compromises cell survival. Although cellular quiescence has been suggested to enhance stress tolerance, its regulatory mechanisms and relevance in NPSCs remain largely unexplored. Methods Oxidative stress was evaluated in human degenerated disc tissues, a rat needle-puncture degeneration model, and tert-butyl hydroperoxide–treated NPSCs in vitro. Proliferating and quiescent NPSCs were compared for reactive oxygen species (ROS) levels, apoptosis, viability, and transcriptomic profiles. Pathway enrichment analyses were performed to identify critical signaling mechanisms. Recombinant transforming growth factor-beta 3 (rhTGF-β3) was used to activate the pathway, while small interfering RNA targeting the transforming growth factor-beta receptor type 2 ( Tgfbr2 ) and the pharmacological inhibitor SB431542 were applied for pathway suppression. Functional assays, organ culture, and in vivo transplantation were conducted to assess cell survival and regenerative effects. Results Elevated oxidative stress was consistently observed across clinical, animal, and cellular models of disc degeneration. Quiescent NPSCs demonstrated enhanced resistance to oxidative injury, with reduced ROS accumulation, decreased apoptosis, and improved survival. Transcriptomic analyses revealed suppression of metabolic and P53-mediated apoptotic pathways, alongside marked activation of TGF-β/SMAD signaling. Activation of this pathway induced quiescence, reduced ROS levels, inhibited mitochondrial apoptotic signaling, and protected NPSCs from oxidative injury, whereas pathway inhibition abolished these protective effects. In both organ culture and in vivo transplantation models, quiescent and TGF-β–activated NPSCs exhibited superior survival and significantly improved disc structural preservation compared with proliferating or pathway-blocked cells. Conclusion Activation of the TGF-β/SMAD pathway induces NPSC quiescence and enhances oxidative stress tolerance by suppressing P53-dependent mitochondrial apoptosis. Pharmacological induction of quiescence represents a potential strategy to improve stem cell–based therapies for intervertebral disc degeneration.
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Pharmaceutics
·
2026
·Vol. 18
·期 3
·363
·
IF 6.9
Meitong Liu,Kai Wang,Can Zeng,Yijiang Jia,Jiaqi Wang,Ayijiang Taledaohan,Yuji Wang,Xiaobing Guan
Purpose:Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic evaluation of its therapeutic efficacy and underlying molecular mechanisms.Materials and Methods:The gelatin/lignin hydrogel was prepared and subsequently loaded with miR-185 EV. The physicochemical properties of the hydrogel, including microstructure, swelling behavior, chemical composition, and rheological characteristics, were systematically evaluated. Next, the stability, viscosity, biocompatibility, and exosome release kinetics of the hydrogel were further assessed. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse tongue carcinogenesis model was established to assess the in vivo antitumor activity of the hydrogel via intraoral administration. Moreover, a proteomic analysis was conducted to investigate the molecular mechanisms of miR-185 EV on OSCC.Results:The miR-185 EV-loaded gelatin/lignin hydrogel exhibited favorable physicochemical properties, stability, and biocompatibility while prolonging the tissue retention time of miR-185 EV. In vivo antitumor efficacy experiments showed that the miR-185 EV-loaded hydrogel significantly inhibited tumor occurrence and alleviated epithelial dysplasia. Immunohistochemical analyses revealed significant suppression of tumor proliferation and epithelial–mesenchymal transition (EMT) of the hydrogel. Proteomic analysis indicated that miR-185 EV suppressed OSCC progression by downregulating interleukin-1β (IL-1β), consequently inhibiting the NF-κB signaling pathway.Conclusion:The findings demonstrate the successful development of the miR-185 EV-loaded gelatin/lignin hydrogel that represents an effective nanomedicine platform for intraoral drug delivery, providing a promising strategy for the clinical treatment of OSCC.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
·
IF 5.9
Liping Zhang,Yanyan Wang,Wenxin Qiu,Shuangling Liu,Shengxuan Xu,Hongwei Wang,Lin Yuan
Neural differentiation of embryonic stem cells (ESCs) holds significant therapeutic potential for the treatment of neurodegenerative diseases. A cell conversion strategy was developed to induce neural differentiation of ESCs by utilizing exosomes (Exo) derived from mesenchymal stem cells (MSCs) as efficient delivery vehicles for retinoic acid (RA) and fibroblast growth factor 2 (FGF2). The abundant surface proteins and phospholipid bilayer of Exo provided protective effects for FGF2 and RA, 88 % of RA remained within the Exo, and the residual amount of exosome-bound FGF2 was nearly 5-fold higher than that of free FGF2, after storage at 4 °C for 5 days. Exo co-loaded with RA and FGF2 exhibited excellent biocompatibility and promoted cell proliferation, resulting in a 3.3-fold higher proliferation over the free RA+FGF2 within 3 days. Neural differentiation was enhanced through dual signaling pathways mediated by RA and FGF2, leading to a nearly 3-fold increase in the relative expression of neuronal marker genes and 8.3-fold increase in the number of differentiated neural cells, compared to the RA+FGF2 group by day 7. This approach significantly enhanced both the efficiency and yield of neural differentiation, presenting a promising nanomedicine strategy by applying engineered Exo to guide the neural lineage commitment of ESCs.
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PubMed
高影响因子
Neural Regeneration Research
·
2023
·Vol. 18
·期 10
·2291
·
IF 6.1
Zhang Zhong-Xia,Zhou Yong-Jie,Gu Ping,Zhao Wei,Chen Hong-Xu,Wu Ruo-Yu,Zhou Lu-Yang,Cui Qing-Zhuo,Sun Shao-Kang,Zhang Lin-Qi,Zhang Ke,Xu Hong-Jun,Chai Xi-Qing,An Sheng-Jun
Microglia -mediated inflammatory responses have been shown to play a crucial role in Parkinson’s disease . In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson’s disease by inhibiting microglia -mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine -induced rat model of Parkinson’s disease . We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1β and interleukin-18 secretion, prevented the adoption of pyroptosis -associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson’s disease , and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.
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BIOMACROMOLECULES
·
2022
·
IF 6.978
Hou Liu,Yubin Feng,Songtian Che,Lin Guan,Xinting Yang,Yue Zhao,Linan Fang,Andrei V. Zvyagin,Quan Lin
Spinal cord injury (SCI) generally leads to long-term functional deficits and is difficult to repair spontaneously. Many biological scaffold materials and stem cell treatment strategies have been explored, but very little research focused on the method of combining exogenous neural stem cells (NSCs) with a biodegradable conductive hydrogel scaffold. Here, a NSC loaded conductive hydrogel scaffold (named ICH/NSCs) was assembled by amino-modified gelatin (NH2-Gelatin) and aniline tetramer grafted oxidized hyaluronic acid (AT-OHA). Desirably, the well-conducting ICH/NSCs can be simply injected into the target site of SCI for establishing a good electrical signal pathway of cells, and the proper degradation cycle facilitates new nerve growth. In vitro experiments indicated that the inherent electroactive microenvironment of the hydrogel could better manipulate the differentiation of NSCs into neurons and inhibit the formation of glial cells and scars. Collectively, the ICH/NSC scaffold has successfully stimulated the recovery of SCI and may provide a promising treatment strategy for SCI repair.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 4
·3850
·
IF 5.6
Chang-Sheng Yang,Xiao-Shuang Guo,Ying-Ying Yue,Yu Wang,Xiao-Lei Jin
The survival of free fat grafts is dependent primarily on adipose-derived stem cells (ADSCs); however, ADSCs are susceptible to oxidative stress in the recipient area. Astaxanthin (Axt) is a natural xanthophyll carotenoid with potent antioxidant properties and numerous clinical applications. To date, the therapeutic potential of Axt in fat grafting has not been explored. The purpose of this study is to investigate the effects of Axt on oxidatively stressed ADSCs. An oxidative model of ADSCs was developed to simulate the host’s microenvironment. Oxidative insult decreased the protein levels of Cyclin D1, type I collagen alpha 1 (COL1A1), and type II collagen alpha 1 (COL2A1), while increasing the expression of cleaved Caspase 3 and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ADSCs. Axt pre-treatment significantly reduced oxidative stress, increased the synthesis of an adipose extracellular matrix, alleviated inflammation, and restored the impaired adipogenic potential in the present model. Furthermore, Axt immensely activated the NF-E2-related factor 2 (Nrf2) pathway, and ML385, an inhibitor of Nrf2, could negate Axt’s protective effects. Additionally, Axt alleviated apoptosis by inhibiting bcl-2-associated X protein (BAX)/Caspase 3 signaling and improving the mitochondrial membrane potential (MMP), which could also be abolished by ML385. Our results suggest that Axt may exert its cytoprotective effect on ADSCs through the Nrf2 signaling pathway and could be therapeutic in fat grafting.Keywords:fat grafting;mesenchymal stem cell;oxidative stress;astaxanthin;Nrf2 signaling pathway;apoptosis
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高影响因子
JOURNAL OF FLUORESCENCE
·
2022
·Vol. 33
·期 2
·739-750
·
IF 2.525
Wang Wenxian,Yang Dan,Zhou Yufei,Zhang Yuding,Guan Lijiao,Zhang Xianfen,Xue Weiming,Huang Saipeng
Tyrosinase (TYR), an important biomarker for melanoma, offered significant information early detection of melanoma and may decrease the likelihood of mortality. Therefore, this article constructed a highly sensitive and selective green fluorescent functionalized carbon quantum dots (TYR-CQDs) for tyrosinase (TYR) activity detection by one-step hydrothermal protocol utilizing catechol, citric acid and urea as precursors. The prepared TYR-CQDs illustrated excellent linear relationship and broad linear range with a low detection limit, which exhibited high accuracy and recovery in quantitative determination of TYR in human serum samples. Furthermore, the TYR-CQDs had successfully realized intracellular TYR detection owing to excellent biocompatibility, high anti-interference ability and good cellular imaging capability, suggesting the potential biomedical applications in early diagnosis of melanoma and other tyrosinase-related diseases. Graphical Abstract
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ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Zhangning Fu,Yanji Chu,Xiaodong Geng,Yingchao Ma,Kun Chi,Chengcheng Song,Shenglong Liao,Quan Hong,Di Wu,Yapei Wang
Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.
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