Regenerative Biomaterials
·
2025
·
IF 8.1
Liu Jun,Liu Qian,Guo Minmei,Jiang Chengyu,Cheng Jianyang,Wang Ting,Sung Tzu-Cheng,Chou Shih-Jie,Chiou Shih-Hwa,Fan Guoping,Higuchi Akon
A variety of novel peptide-grafted hydrogels, of which peptides were derived from vitronectin (PQVTRGDVFTMP) or the laminin β4 chain (PMQKMRGDVFSP) were prepared in this study. The peptide-grafted hydrogels promoted the adhesion, proliferation, and colony formation of hiPSCs and maintained their pluripotency up to passage 5 under xeno-free conditions. We successfully generated RPE cells from hiPSCs on one of the most suitable xeno-free peptide-grafted hydrogels, KVN2CK (KGCGGKGG-PQVTRGDVFTMP), which derived from vitronectin, and confirmed the effect of these hiPSC-derived RPE cells in a rat retinal degeneration model (Royal College of Surgeons (RCS) rats) via subretinal transplantation, when we investigated functional improvements in vision in RCS rats after the transplantation of hPSC-derived RPE cells. Our novel peptide-grafted hydrogels provided a safe and robust platform for generating single-layer hiPSC-derived RPE cells under xeno-free conditions, which indicates the potential of these hydrogels for stem cell therapy for retinal degenerative diseases in future.
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Duoduo Zhang,Kunying Chen,Yongkang Yu,Ruting Feng,Steve W. Cui,Xingtao Zhou,Shaoping Nie
Metabolites of dietary fibers which consist of non-digestible carbohydrates (usually as plant-based polysaccharides) exert many benefits on gastrointestinal health. Previous studies proved that polysaccharides can change intestinal metabolic pathways, increase metabolite levels and alleviate intestinal inflammation. Our previous studies have shown that polysaccharide from Aloe vera gel (AGP) alleviated intestinal barrier dysfunction. However, whether intestinal protective function of AGP was related to metabolites need further exploration. Therefore, the effects of AGP on intestinal metabolites and the relevant mechanisms for subsequent mitigation of intestinal damage was investigated in this work. Metabolomics analysis results showed that AGP promoted tryptophan metabolism to 5-hydroxytryptamine (5-HT). Intriguingly, antibiotics treatment decreased the expression of tryptophan hydroxylase 1 (TPH1) in the intestinal epithelium of mice, and TPH1 inhibitor (PCPA) down-regulated 5-HT level in colonic contents, proving that AGP up-regulated TPH1 expression in the intestinal epithelium by restoring intestinal microbiota homeostasis, thus promoted the intestinal tryptophan metabolism to 5-HT. Combination of bioinformatics analysis of RNA-sequencing (RNA-Seq) in mice colon and the reported relationship among “5-HT, Htr4 (one of the 5-HT receptors), Kit + goblet cells, canonical Wnt pathway and intestinal stem cells (ISCs)” guided the confirmation of related mechanism in intestinal organoids (IOs) that 5-HT regulated ISCs function and intestinal barrier via Htr4-Kit-Wnt3 axis. Overall, AGP promoted 5-HT production to alleviate intestinal injury. This study revealed the effects of polysaccharides on intestinal health, which was critical and may provide new insights for the reasonable selection of dietary fiber to prevent intestinal inflammation and maintain intestinal function.
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高影响因子
CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Yifei Zhang,Kang Liu,Xuejing Ma,Xiangchen Su,Liang Zhao,Yi Wu,Yijie Shi
Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. The primary objective of this study was to assess the therapeutic potential of puerarin loaded bone marrow mesenchymal stem cell-derived exosomes (Pue@BMSC-Exo), and reveal their inflammatory regulating mechanisms through affecting the nuclear factor kappa-B (NF-κB) signaling pathway. In this study, e xosomes derived from BMSCs were isolated and identified. Cell proliferation and migration were evaluated by CCK-8 and scratch methods. Furthermore, histological and micro-computed tomography analysis were performed to assess alterations of articular cartilage in OA rats. Results showed that BMSC-Exo and Pue@BMSC-Exo conformed with the basic characteristics of exosomes. BMSC-Exo increased the solubility of Pue and enhanced drug uptake by chondrocytes. In addition, Pue@BMSC-Exo stimulated proliferation and migration of chondrocyte, and also promoted cartilage repair by reducing matrix metalloproteinase MMP13 production and increasing type II collagen (Col2) synthesis. Furthermore, Pue@BMSC-Exo, by effectively inhibiting the NF-κB signaling pathway, reduced the production of inflammatory mediators and attenuated the release of the inflammatory marker nitric oxide (NO), ultimately ameliorating the damage of chondrocyte. These findings exhibited the potential therapeutic significance of Pue@BMSC-Exo in OA and warranted further exploration in clinical applications. Graphical
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shun Yu,Ying Luo,Xiaoli Jia,Pan Du,Zili Sun,Yuying Wang,Guozhong Lyu,Chenyang Liu
Our previous research established that treatment with IFN-γ and TNF-α (IT) significantly enhanced the paracrine activity of MSCs, resulting in a more effective wound healing response when applied to the wound surface with supernatant from IT-stimulated MSCs (S-IT MSCs). While S-IT MSCs hold promise for advancing wound healing therapy, challenges remain in developing an approach that enhances therapeutic efficacy and simplifies administration. This study proposed a scaffold composed of sericin, known for its skin regeneration properties, to load S-IT MSCs, designated as Se + S-IT MSCs, for the protection of bioactive factors. Additionally, whether Se + S-IT MSCs exhibit a superior effect on wound healing was investigated using a rat total skin excision model. Results indicated that Se + S-IT MSCs outperformed silk sericin loaded with MSC supernatant (Se + S-MSCs) in promoting migration, proliferation, and activation of HUVECs, HaCaTs, macrophages, and HDFs. Furthermore, Se + S-IT MSCs significantly promoted macrophage polarization toward the M2 phenotype, potentiated vascularization and re-epithelialization, and enhanced collagen deposition. These effects collectively accelerated wound healing in vivo in rats. This study highlights the potential of Se + S-IT MSCs to facilitate rapid and effective wound healing, with silk sericin scaffolds serving as efficient carriers to expedite the process.
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ACS Nano
·
2025
·
IF 16
Fan Chen,Wenzhe Wang,Hengxin Zhao,Zian Zhang,Nanyu Pang,Yijie Tang,Tian Wang,Chang Liu,Zhenchao Huang,Feiyu Mou,Chaoqun Yu,Haining Zhang
Intra-articular drug injection is an effective treatment for osteoarthritis (OA). However, the rapid clearance of drugs from the joint cavity results in low drug utilization and suboptimal therapeutic outcomes. This study describes MXene-based cartilage-adhesive microspheres for photothermal-controlled hydrophobic drug release and bone marrow mesenchymal stem cell (BMSC) delivery. Nano cationic amylose (NCA) was obtained by modifying amylose with glycidyltrimethylammonium chloride (GTAC), and hydrophobic drug Kartogenin (KGN) was encapsulated in the hydrophobic helical cavity of NCA through ultrasonic treatment, resulting in nano cationic amylose@KGN complexes (NCA@KGN). HAMA/MXene-NCA@KGN (H/M-NCA@KGN) microspheres were prepared using a microfluidic device. These microspheres exhibited excellent biocompatibility, effectively adhered to the cartilage surface, and carried BMSCs. H/M-NCA@KGN microspheres demonstrated photothermal-controlled release of the hydrophobic drug KGN. Notably, KGN promoted the differentiation of BMSCs into chondrocytes, thereby improving the loss of extracellular matrix in joint cartilage. Additionally, appropriate thermal stimulation induced the expression of heat shock protein 70 (HSP70) in OA chondrocytes, providing a protective effect and delaying the progression of OA. H/M-NCA@KGN microspheres enable controlled hydrophobic drug release and stem cell delivery for potential OA treatment applications.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2017
·Vol. 27
·期 11
·1604992
·
IF 12.124
Shu-Qi Wu,Cheng-Xiong Yang,Xiu-Ping Yan
Therapeutically engineered mesenchymal stem cells (MSC) have shown promising capability for glioblastoma (GBM) therapy; however, simultaneous tracking of their migration and long-term fate is urgently needed for clinical application. This study shows the design and fabrication of a dual-functional persistent luminescence nanocomposite (LPLNP-PPT/TRAIL) for effective therapeutic engineering and tracking of MSC in the meantime. LPLNP-PPT/TRAIL shows low-toxicity, near-infrared persistent luminescence emitting without in situ excitation, and superior in vivo deep brain tissue imaging, which can efficiently track the tumortropic migration of the therapeutic engineered MSC. Both in vitro and in vivo findings demonstrate the feasibility of LPLNP-PPT/TRAIL engineered MSC for inducing apoptosis of glioblastoma cells. This work first establishes an LPLNP-based dual-functional platform for cell engineering and provides us implications for GBM-related diagnosis and therapy.
研究领域:
生物医学工程
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癌症研究
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纳米技术
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干细胞生物学
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Stem Cells International
·
2023
·
IF 4.3
Ruixi Luo,Yaqiong Wei,Peng Chen,Jing Zhang,La Wang,Wenjia Wang,Ping Wang,Weiyi Tian
Background. Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease, and it carries a poor prognosis due to a lack of efficient diagnosis methods and treatments. Epithelial-mesenchymal transition (EMT) plays a key role in IPF pathogenesis. Endoplasmic reticulum (ER) stress contributes to fibrosis via EMT-mediated pathways. Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for pulmonary fibrosis and ameliorates lung fibrosis in animal models via paracrine effects. However, the specific mechanisms underlying the effect of transplanted MSCs are not known. We previously reported that MSCs attenuate endothelial injury by modulating ER stress and endothelial-to-mesenchymal transition. The present study investigated whether modulation of ER stress- and EMT-related pathways plays essential roles in MSC-mediated alleviation of IPF. Methods and Results. We constructed a A549 cell model of transforming growth factor-β1 (TGF-β1)-induced fibrosis. TGF-β1 was used to induce EMT in A549 cells, and MSC coculture decreased EMT, as indicated by increased E-cadherin levels and decreased vimentin levels. ER stress participated in TGF-β1-induced EMT in A549 cells, and MSCs inhibited the expression of XBP-1s, XBP-1u, and BiP, which was upregulated by TGF-β1. Inhibition of ER stress contributed to MSC-mediated amelioration of EMT in A549 cells, and modulation of the IRE1α-XBP1 branch of the ER stress pathway may have played an important role in this effect. MSC transplantation alleviated bleomycin (BLM)-induced pulmonary fibrosis in mice. MSC treatment decreased the expression of ER stress- and EMT-related genes and proteins, and the most obvious effect of MSC treatment was inhibition of the IRE1α/XBP1 pathway. Conclusions. The present study demonstrated that MSCs decrease EMT by modulating ER stress and that blockade of the IRE1α-XBP1 pathway may play a critical role in this effect. The current study provides novel insight for the application of MSCs for IPF treatment and elucidates the mechanism underlying the preventive effects of MSCs against pulmonary fibrosis.
研究领域:
肺病学
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细胞生物学
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干细胞研究
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分子生物学
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病理生理学
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Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Yujie Zhang,Chuanfeng An,Yang Zhang,Haoyue Zhang,Abdullah Faqeer Mohammad,Qiao Li,Weijian Liu,Fei Shao,Jiayi Sui,Changle Ren,Kai Sun,Fang Cheng,Jia Liu,Huanan Wang
Cell microenvironment is a collection of dynamic biochemical and biophysical cues which functions as the key factor in determining cell behavior. Encapsulating single cell into micrometer-scale hydrogels which mimics the cell microenvironment can be used for single cell analysis, cell therapies, and tissue engineering. Here, we developed a microfluidics-based platform to engineer the niche environment at single cell level using alginate microgels crosslinked by different metal ions to regulate stem cell behavior for bone regeneration. Specifically, we revealed that Ca 2+ in the engineered microenvironment promoted osteogenic differentiation of encapsulated stem cells and substantially accelerated the matrix mineralization compared to Sr 2+ in vitro . However, the superior osteoinductive capacity of Ca 2+ compared with Sr 2+ led to comparable bone healing in a rat bone defect model. This attributed to Sr 2+ in microgels to inhibit the osteoclast activity and bone resorption after implantation. In summary, the present study demonstrates metal ions as a critical factor in the environmental cues to affect cell behavior and influence the efficacy of stem cell-based therapy in tissue regeneration, and provides new insights to engineer an expecting microenvironment for regenerative medicine.
研究领域:
组织工程
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干细胞生物学
·
再生医学
·
生物医学工程
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高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2020
·
IF 2.751
Xia Zhao,Xiang Xu,Xue-gui Wang,Yong Yin,Ming-yang Li,Ya-qiong Wu,Ying-hong Liu,Qing-hua Cheng,Chang-wei Gong,Li-tao Shen
Chilo suppressalis Walker (Lepidoptera: Crambidae) is a widely destructive pest occurring in rice, particularly in the rice-growing regions of Asia. In recent years, C. suppressalis has developed resistance to several insecticides because of the extensive use of insecticides. The resistance levels to four insecticides were determined among populations from different regions of Sichuan Province, China, using a drop-method bioassay. Based on LC 50 values of a laboratory susceptible strain, all field populations showed moderate level of resistance to triazophos (23.9- to 83.5-fold) and were either susceptible or had a low level of resistance to abamectin (2.1- to 5.8-fold). All field-collected populations had a low or moderate level of resistance to chlorpyrifos (1.7- to 47.1-fold) and monosultap (2.7- to 13.5-fold). The synergism experiment indicated that the resistance of the XW19 to triazophos may be associated with cytochrome P450 monooxygenases (P450s), with the highest synergistic ratio (SR) of 3.05-fold and increased ratio (IR) of 2.28-fold for piperonylbutoxide (PBO). The P450 activity of the TJ19 population was the greatest among the six field populations. Moreover, the relative expression levels of four resistance-related P450 genes were detected with qRT-PCR, and the results indicated that CYP324A12 , CYP321F3 and CYP9A68 were overexpressed in the resistant population, especially in the XW19 population (by 1.2-, 3.4 -, and 18.0-fold, respectively). In addition, the relative expression levels of CYP9A68 among the CZ19 and TJ19 populations were also enhanced 10.5- and 24.9-fold, respectively. These results suggested that CYP324A12 , CYP321F3 and CYP9A68 may be related to the resistance development of C. suppressalis to triazophos.
研究领域:
昆虫学
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害虫管理
·
分子生物学
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高影响因子
ACS Nano
·
2020
·
IF 14.588
Yiqi Gong,Zhuoyue Chen,Li Yang,Xuefeng Ai,Bingqian Yan,Huijing Wang,Liya Qiu,Yao Tan,Nevin Witman,Wei Wang,Yuanjin Zhao,Wei Fu
Stem-cell based in vitro differentiation for disease modeling offers great value to explore the molecular and functional underpinnings driving many types of cardiomyopathy and congenital heart diseases. Nevertheless, one major caveat in the application of in vitro differentiation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) involves the immature phenotype of the CMs. Most of the existing methods need complex apparatus and require laborious procedures in order to monitor the cardiac differentiation/maturation process and often result in cell death. Here we developed an intrinsic color sensing system utilizing a microgroove structural color methacrylated gelatin film, which allows us to monitor the cardiac differentiation process of hiPSC-derived cardiac progenitor cells in real time. Subsequently this system can be employed as an assay system to live monitor induced functional changes on hiPSC-CMs stemming from drug treatment, the effects of which are simply revealed through color diversity. Our research shows that early intervention of cardiac differentiation through simple physical cues can enhance cardiac differentiation and maturation to some extent. Our system also simplifies the previous complex experimental processes for evaluating the physiological effects of successful differentiation and drug treatment and lays a solid foundation for future transformational applications.
研究领域:
干细胞生物学
·
心血管研究
·
生物医学工程
·
药物开发
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高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Xiaojing Yuan,Zuoying Yuan,Yuanyuan Wang,Zhuo Wan,Xiaotong Wang,Shi Yu,Jianmin Han,Jianyong Huang,Chunyang Xiong,Lihong Ge,Qing Cai,Yuming Zhao
Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide- co -glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O 1 /W/O 2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.
研究领域:
牙科学
·
组织工程
·
再生医学
·
干细胞生物学
·
材料科学
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高影响因子
Nanoscale
·
2018
·Vol. 10
·期 27
·13106-13121
·
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
·
纳米技术
·
药学
·
癌症生物学
·
神经科学
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高影响因子
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