INFECTION AND IMMUNITY
·
2018
·Vol. 86
·期 6
·
IF 3.256
Zhemin Wang,Xiaomin Wang,Ping Lu,Chunshan Ni,Yuezhou Li,Stijn van der Veen
Mechanosensitive channels are ubiquitous in bacteria and provide an essential mechanism to survive sudden exposure to a hypo-osmotic environment by the sensing and release of increased turgor pressure. No mechanosensitive channels have thus far been identified and characterized for the human-specific bacterial pathogen Neisseria gonorrhoeae. In this study, we identified and characterized the N. gonorrhoeae MscS-like mechanosensitive channel (Ng-MscS). Electrophysiological analyses by the patch clamp method showed that Ng-MscS is stretch activated and contains pressure-dependent gating properties. Further mutagenesis studies of critical residues forming the hydrophobic vapor lock showed that gain-of-function mutations in Ng-MscS inhibited bacterial growth. Subsequent analysis of the function of Ng-MscS in N. gonorrhoeae by osmotic down-shock assays revealed that the survival of Ng-mscS deletion mutants was significantly reduced compared with that of wild-type strains, while down-shock survival was restored upon the ectopic complementation of mscS. Finally, to investigate whether Ng-MscS is important for N. gonorrhoeae during infections, competition assays were performed by using a murine vaginal tract infection model. Ng-mscS deletion mutants were outcompeted by N. gonorrhoeae wild-type strains for colonization and survival in this infection model, highlighting that Ng-MscS contributes to in vivo colonization and survival. Therefore, Ng-MscS might be a promising target for the future development of novel antimicrobials.
研究领域:
微生物学
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细菌生理学
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传染病学
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离子通道生物学
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DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Zetao Wang,Ruiming Liang,Xianfang Jiang,Jiali Xie,Peian Cai,Haimin Chen,Xintang Zhan,Danqing Lei,Jinmin Zhao,Li Zheng
Nanofibers as niche-biomimetic scaffolds hold promise in guided bone regeneration (GBR). Here we fabricated poly (lactic- co -glycolic acid) (PLGA)/poly(caprolactone) (PCL)-doped octacalcium phosphate (OCP) nanofiber membranes via electrospinning and investigated the osteogenic behavior of marrow mesenchymal stem cells (MSCs) on the membranes. By adjusting different ratio of OCP to PLGA/PCL, three hybrid stents including PLGA/PCL, PLGA/PCL/2 wt%OCP, PLGA/PCL/4wt%OCP were successfully prepared. The PLGA/PCL/OCP membranes showed a decrease in fiber diameter compared with PLGA/PCL, leading to enhanced mechanical strength. In-vitro studies showed that PLGA/PCL/OCP membranes better supported cell adhesion, spreading and proliferation than PLGA/PCL. The incorporation of OCP via electrospinning also endowed the membranes with osteoinductive capacity, as evidenced by activation of ALP activity, increased gene expression of bone specific markers (such as Runx2 , ALP , Col 1a1 , OPN , OCN , BMP2 ), and mineral nodules formation compared to PLGA/PCL. Comparatively, PLGA/PCL/4wt%OCP showed better mechanical and biological performance than PLGA/PCL/2 wt%OCP, demonstrating the role of OCP in nanofiber membranes. Thus, the electrospun PLGA/PCL/OCP nanofiber membranes can be potentially developed as a promising hybrid stent for GBR.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
生物医学工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 34
·7713-7722
·
IF 5.344
Long Gao,Min Yi,Min Xing,Hekai Li,Yanling Zhou,Qing Xu,Zhaowenbin Zhang,Zhanpeng Wen,Jiang Chang
Stem-cell therapy has been proved as a promising strategy for myocardial infarction (MI) treatment. However, the therapeutic efficacy is mainly limited by the cellular activity of transplanted mesenchymal stem cells (MSCs). In this study, a novel bioglass (BG)/γ-polyglutamic acid (γ-PGA)/chitosan (CS) hydrogel was obtained by in situ adding BG to stimulate the imine bond formation. And the effect of the composite hydrogel on MI therapeutic efficacy was evaluated in a rat acute myocardial infarction (AMI) model in vivo and the possible mechanism of the BG/γ-PGA/CS hydrogel for the stimulation of the intercellular interaction between MSCs and cardiomyocytes (CMs) was explored by a MSC and CM co-culture experiment in vitro. The implantation of the MSC loaded BG/γ-PGA/CS composite hydrogel in the mice AMI model showed a significant improvement in the therapeutic efficacy with improved cardiac function, attenuation of heart remodeling, reduced cardiomyocyte apoptosis and accelerated vascularization. The in vitro cell experiments demonstrated that the BG/γ-PGA/CS hydrogel activated the intercellular interaction between MSCs and CMs, which resulted in reduced cell apoptosis and enhanced angiogenesis. Silicate based bioactive hydrogels activated MSCs and cell–cell interactions in cardiac tissue after AMI and significantly enhanced the efficacy, which suggests that this bioactive hydrogel based approach is an effective way to enhance stem-cell therapy.
研究领域:
生物医学工程
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组织工程
·
干细胞治疗
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心脏病学
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DOI
PubMed
高影响因子
Science Bulletin
·
2025
·
IF 21.1
Min Nie,Danqing Huang,Dandan Wang,Yuanjin Zhao,Lingyun Sun
Refractory wounds (RWs) are a common and severe complication of many diseases; however, the existing therapeutic methods are unsatisfactory in clinical practice. Here, we observed significant downregulation of the hepatocyte growth factor (HGF) in plasma samples from patients with autoimmune diseases. We used electroporation to deliver a plasmid containing HGF to induce its overexpression on mesenchymal stromal cells (MSC HGF ) and loaded them into an injectable hydrogel to treat RWs in patients with clinical autoimmunity. The MSC HGF exhibited stable HGF expression and secretion. In addition, they displayed a self-reinforcing loop, enhanced migration, and improved anti-apoptosis capacity via the autocrine activation of the c-Met-mediated phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Furthermore, the HGF (as well as other bioactive factors) secreted from the MSC HGF significantly augmented the migration and angiopoiesis of vascular endothelial cells, decreased the cellular inflammation of macrophages, and improved extracellular matrix remodeling in fibroblasts. According to these features, we demonstrated that the MSC HGF -loaded injectable hydrogel boosted cellular functions and afforded a long-acting healing efficacy in the treatment of clinical autoimmune patients with RWs. Therefore, the genetically engineered MSC HGF and their dispersed hydrogel system will have clinical significance for wound therapy.
研究领域:
再生医学
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基因治疗
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伤口愈合
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干细胞治疗
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Xinkun Shen,Yonglin Yu,Pingping Ma,Zhong Luo,Yan Hu,Menghuan Li,Ye He,Yangyang Zhang,Zhihong Peng,Guanbin Song,Kaiyong Cai
Before mesenchymal stem cells (MSCs) adhere to the surface of an implant and differentiate into osteoblasts, monocytes (especially macrophages) arrive at the bone injury site and interact with the implant and subsequent MSCs. In our previous study, large titania nanotubes (TNT 110 ) had been verified to endow superior oxidation resistance to osteoblasts. The early regulation between macrophages and MSCs by surface nanotubes under oxidative stress (OS) was evaluated further in this study. Cellular and molecular results show that TNT 110 greatly increased early inflammation of macrophages by activating integrin/FAK-mediated MAPK and NFκB signals and simultaneously promoted their gene expression of SDF1, IL-8, and CCL2 (chemokines) compared with 30 nm nanotubes and titanium substrates. Co-culture results show that more MSCs were recruited by those chemokines and may promote osteogenic self-differentiation, reducing early inflammation of macrophages by accelerating their M1-to-M2 transition in the TNT 110 group. All findings reveal that the early cellular behavior of macrophages and MSCs was effectively regulated by TNT 110 , indicating large nanotubes would be more suitable to prevent oxidative damages.
研究领域:
生物材料
·
细胞生物学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Zhenguang Li,Li Peng,Laiya Lu,Yingying Wang,Xiaolei Chen,Feng Yin,Cuijun Deng,Yu Cheng
Mechanical signals play a fundamental role in regulating stem cell fate. However, due to the lack of spatiotemporal mechanical tools, directing the in situ chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) remains a formidable challenge in articular cartilage repair. Here, we develop a magneto-mechanical stimulation platform with unique 3D actuation to orchestrate chondrogenic commitment of endogenous BMSCs. The BMSC-targeted antioxidative magnetic nanomotors are designed to perform trans-planar rotational-bouncing motions in lysosomes under a self-developed 3D rotating fluctuating magnetic field, generating amplified dynamic mechanical stimulation. They potentiate chondrogenic differentiation of BMSCs by lysosomal mechanically-gated actin cytoskeletal remodeling. After intra-articular delivery of nanomotors via an injectable hydrogel, they can target endogenous BMSCs and be wirelessly controlled to apply the dynamic mechanical stimulation in vivo for hyaline cartilage regeneration. Beyond cartilage repair, this platform offers a generalized methodology to remotely regulate the mechanical signals of cell fate for regenerative medicine.
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Yi Wu,Xuan Li,Shaopeng Liu,Ruichen Ma,Peng Liu,Kaiyong Cai
Bone repair in elderly patients is significantly weaker compared to normal bone repair, and one of the main reasons for this is the senescence of bone marrow mesenchymal stem cells (MSCs), which play a key role in the bone repair process. Therefore, we considered the corresponding surface modification of orthopedic implants to cope with the practical problem of bone defects in elderly patients. In this thesis, we prepared TiO 2 nanotubes loaded with metformin (Glucophage) on Ti substrates, followed by self-assembly layer by layer using chitosan-catechol and gelatin on the surface, to delay MSCs senescence by eliminating excessive reactive oxygen species (ROS) and reconstructing extracellular matrix (ECM), thereby achieving osteogenesis. The results showed a significant reduction in senescence-associated secretory phenotype (SASP) generation, an enhancement of PINK1/Parkin-mediated mitochondrial autophagy, and a decrease in intracellular and extracellular ROS levels in MSCs under the dual effects of antioxidants and ECM reconstruction, suggesting that the degree of senescence in MSCs was significantly reduced. Osteogenesis was also demonstrated by expression of osteogenesis-related genes and staining of animal sections. In conclusion, our material can indeed promote the proliferation and osteogenic differentiation of MSCs by delaying cellular senescence, which is expected to provide a novel approach for clinical solutions to tissue repair problems in elderly patients with bone defects.
研究领域:
骨科
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生物材料
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组织工程
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干细胞生物学
·
老年医学
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DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Yu Ren,Aili Aierken,Li Zhao,Zhuangsheng Lin,Jingjing Jiang,Balun Li,Jinyi Wang,Jinlian Hua,Qin Tu
In this study, we used the polysaccharide ulvan from the green macroalgae Ulva fenestrata to prepare the hydrogel for chronic diabetic wound healing. A natural polysaccharide-based hydrogel matrix (UC-DPA-Ag hydrogel) was prepared using ulvan dialdehyde, chitosan, dopamine (DPA) and silver nanoparticles (Ag NPs). Human umbilical cord mesenchymal stem cell lyophilized powder (hUC-MSCs) was loaded into the hydrogel to develop a novel chronic diabetic wound healing material ( [email protected] ). The resulting hydrogel features adequate mechanical properties, swelling capability, adhesiveness, antioxidant , antibacterial ability, and promoting cell proliferation and migration. In vivo wound healing in type II diabetic mellitus mouse wound model showed that hUC-MSCs loaded UC-DPA-Ag hydrogel could accelerate wound healing effectively. This advanced hydrogel provides a facile and effective way for diabetic chronic wound management. Furthermore, it offers a new route for the utilizing Ulva as a valuable biomaterial for the global and large-scale production of valued added biomaterials.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-13
·
IF 10.435
Yin Yipengchen,Li Yongjing,Wang Sheng,Dong Ziliang,Liang Chao,Sun Jiaxin,Wang Changchun,Chai Rong,Fei Weiwei,Zhang Jianping,Qi Ming,Feng Liangzhu,Zhang Qin
Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T 1 -weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.
研究领域:
纳米技术
·
生物医学工程
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 12.9
Aohua Li,Yi Zhu,Saidur Rahaman,Ailing Hao,Yannian Gou,Xiangyu Dong,Han Xiang,Jiajia Li,Yiheng Qiu,Caiyun Zhang,Senjie Xu,Jiaming Zhong,Xingye Wu,Yi Shu,Chao Yu,Yan Peng,Yuting Liang,Sarina Zhao,Michelle Xiang,Wonyong Lee,Sofia Bougioukli,Gregory Schimizzi,Russell R. Reid,Xiaosong Li,Tong-Chuan He,Jiaming Fan
Effectively healing of large bone defects is a clinical challenge. Extracellular vesicle (EV)-mediated cell-free therapy has great potential in bone defect repair; however, unmodified EVs generally exhibit limited osteogenic potential. Bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic cytokines reported to date. Here, we modified the EVs from BMP9-stimulated adipose-derived mesenchymal stem cells (iMAD), designated as B9-EVs. Subcutaneous injections of B9-EVs in immune-competent mice elicited no detectable host immune response. B9-EVs effectively induced in vitro osteogenic markers and promoted subcutaneous bone formation and cranial defect repair in vivo , similar to the direct use of recombinant adenovirus-mediated BMP9 over expressing (AdR-B9) transduced iMAD cells. The miRNA-seq analysis of B9-EVs identified a distinct set of osteogenesis-related miRNAs. RNA-seq analysis revealed that osteogenesis-associated transcripts regulated in B9-EVs-stimulated MSCs were overlapping with but also distinct from those in AdR-B9-stimulated MSCs. Further bioinformatic analysis established a miRNA-mRNA network and revealed that the functionalized B9-EVs may regulate 10 miRNAs and 11 mRNA transcripts to induce osteogenesis through mechanisms that are unique and distinct from those associated with direct BMP9 stimulation. Collectively, given the cell-free and non-immunogenic nature, the functionalized osteogenic B9-EVs hold great potential for bone tissue engineering by providing effective osteogenic factors through EV-mediated paracrine signaling mechanism.
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Wang Zixian,Zhang Xiuxiu,Xue Limin,Wang Gangwei,Li Xinda,Chen Jianwei,Xu Ruxiang,Xu Tao
Biopolymer microbeads present substantial benefits for cell expansion, tissue engineering, and drug release applications. However, a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation, passaging, harvesting and downstream application is limited. Therefore, we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers (GMs) for mesenchymal stromal cells (MSCs) expansion and tissue engineering. Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment, expansion and harvest, and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency. Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase, respectively. Furthermore, we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds. These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture, expansion and tissue engineering.
研究领域:
生物技术
·
组织工程
·
细胞生物学
·
材料科学
·
微流控
✓ 已验证
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Kai Yang,Ying-yi Luan,Shan Wang,You-sheng Yan,Yi-peng Wang,Jue Wu,Yong-qing Sun,Jing Zhang,Wen-qi Chen,Yu-lan Xiang,Ze-lu Li,Dong-liang Zhang,Cheng-hong Yin
Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo . In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.
研究领域:
细胞生物学
·
骨再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）