Small
·
2024
·
IF 13
Zhen Zhan,Yuting Wang,Hanhan Xie,Ming Yang,Muyang Ruan,Xuefei Liu,Jialing Liu,Zeyang Liu,Feiqiu Wen,Xin Hong,Chengzhi Hu
Chronic wound poses a serious risk to diabetic patients, primarily due to damaged skin microvasculature and prolonged inflammation at the wound site. Mesenchymal stem cell (MSC) therapy utilizing microgels as a cell delivery system has shown promise in promoting wound healing by enhancing cell viability and the secretion of bioactive factors. Retaining sufficient MSCs at injury sites is crucial for optimal therapeutic outcomes. However, inadequate hierarchical structure and limited use of the microgel's interior space significantly reduce cell proliferation and infiltration efficiency, thereby compromising the therapeutic effect. To address this, a microfluidic approach is developed for fabricating porous hierarchical interconnected microgels with interior spiral canals (PHIGels) by employing a fluidic “viscous instability” effect and gas formation reaction during the microfluidic synthesis. These MSC-laden PHIGel scaffolds facilitate rapid proliferation and infiltration into the interior spiral canals through a hierarchical pore network, significantly increasing the number of viable cells that can be carried by the microgels. It is proved that these microgel-based deliveries of MSCs promote re-epithelialization, collagen synthesis, angiogenesis, and reduction in inflammation, thus enhancing cutaneous wound repair in a rat model of type I diabetes. The microporosity and hierarchical design of these microgels offer novel routes for tissue regeneration and repair.
研究领域:
生物医学工程
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组织工程
·
干细胞疗法
·
伤口愈合
·
糖尿病研究
·
微流控技术
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DOI
PubMed
高影响因子
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
·
2014
·Vol. 61
·期 10
·1161-1167
·
IF 0.856
Lu Han,Chengjie Sun,Jian Lin,Fei Li,Xican Li,Zisheng Wu,Chengping Liu,Ye Bai,Wenqiong Mai,Dongfeng Chen
Herba Ecliptae (HE) is a typical Chinese herbal medicine used in China for 1500 years. In the study, HE was extracted by various solvents to prepare five HE extracts. They were observed to possess a protective effect against ×OH-induced DNA damage, and scavenging effects on ×OH radical, ×O 2 − radical, DPPH×(1,1-diphenyl-2-picrylhydrazyl) radical, and ABTS× + (2,2′-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) radical, and reduce Cu 2+ ion. The contents of total phenolics and wedelolactone in five extracts were determined respectively using Folin-Ciocalteu method and HPLC method. To identify which chemical component can be responsible for its effects, the correlation graphs between chemical contents and antioxidant abilities (1/IC 50 values) were plotted to calculate correlation coefficients (R values). Finally, MTT assay revealed that two HE extracts could effectively protect mesenchymal stem cells (MSCs) against ×OH-induced damage at 3-30 μg/mL. On the basis of mechanistic analysis, we concluded that: ( i ) HE can effectively protect against ×OH-induced damages to DNA and MSCs, thereby HE may have a therapeutic potential in MSCs transplantation or prevention of many diseases; ( ii ) the effects can be mainly attributed to total phenolics (R = 0.678) especially wedelolactone (R = 0.618); ( iii ) they exert antioxidant action via hydrogen atom transfer (HAT) and sequential electron proton transfer (SEPT) mechanisms.
研究领域:
药理学
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生物化学
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细胞生物学
·
中药学
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DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 12
·3286-3300
·
IF 6.183
Dong Xu,Yuxin Wan,Zhihao Li,Chunbao Wang,Qingxia Zou,Chang Du,Yingjun Wang
Hydroxyapatite (HA) micro/nano particles show great promise as artificial bone and dental substitutes, or drug carrier systems. However, the precise regulation of hydroxyapatite micro/nano particles with controllable physicochemical properties (such as hierarchical structure, particle size, potential and crystallinity) is still a challenge. Furthermore, the effects of different hierarchical structures on biological responses have been rarely reported. Herein, the HA particles with a precisely tailored micro/nano hierarchical structure have been developed using an elaborate biomimetic synthesis technology. Three representative particles, namely, micro/nano needle-like HA particles, micro/nano rod-like HA particles, and micro/nano flake-like HA particles, were featured to evaluate their biological responses to stem cells. The pore structure facilitated the adsorption of serum adhesive proteins, which together with the unique hierarchical architecture of micro/nano flake-like HA particles remarkably promoted the endocytosis efficiency in a concentration-dependent manner. The qRT-PCR together with RNA-seq and western blot analyses showed that micro/nano flake-like HA particles more significantly up-regulated the expression of genes and production of proteins related to osteogenic differentiation among the three particles through the activated ERK/MAPK signalling pathway. RNA-seq further revealed a complex mechanism of cell interface events, suggesting that the hierarchical architecture of HA particles is of crucial importance for the regulation of actin cytoskeleton involved in the modulation of cell adhesion which positively stimulated osteogenic differentiation of stem cells. Moreover, the endocytosis of particles into lysosomes resulted in an increase in the intracellular Ca2+ levels, which activated possible intracellular Ca2+-mediated signaling cascades (Ras/cAMP/Rap1/MAPK signaling pathways) related to osteogenic differentiation of stem cells. Our findings shed light on the effects of different hierarchical structures of HA particles on stem cell differentiation and contribute to the optimal design of implant materials.
研究领域:
生物材料
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干细胞生物学
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组织工程
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材料科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Jing Zhang,Juan Gao,Xianlong Li,Dengna Lin,Zhihui Li,Jialei Wang,Junfeng Chen,Zhiliang Gao,Bingliang Lin
Balancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed to investigate the efficacy of human bone marrow MSC-derived sEVs (BMSC-sEVs) in treating mice with ALF and the molecular mechanisms involved in regulating hepatocyte proliferation and apoptosis. Small EVs and sEV-free BMSC concentrated medium were injected into mice with LPS/D-GalN-induced ALF to assess survival, changes in serology, liver pathology, and apoptosis and proliferation in different phases. The results were further verified in vitro in L-02 cells with hydrogen peroxide injury. BMSC-sEV-treated mice with ALF had higher 24 h survival rates and more significant reductions in liver injury than mice treated with sEV-free concentrated medium. BMSC-sEVs reduced hepatocyte apoptosis and promoted cell proliferation by upregulating miR-20a-5p, which targeted the PTEN/AKT signaling pathway. Additionally, BMSC-sEVs upregulated the mir-20a precursor in hepatocytes. The application of BMSC-sEVs showed a positive impact by preventing the development of ALF, and may serve as a promising strategy for promoting ALF liver regeneration. miR-20a-5p plays an important role in liver protection from ALF by BMSC-sEVs.
研究领域:
干细胞生物学
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分子生物学
·
肝病学
·
再生医学
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DOI
PubMed
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Mengjiao Ma,Guodong Liu,Haoye Meng,Yudong Zheng,Jiang Peng,Yajie Xie,Yansen Wang,Wei He,Shuai Wei
In regenerating and repairing the nerve injured by the congenital malformation or trauma, the conundrum of electrical signal transmission between the nerve cells in damaged nerve tissue remains an uncrossable barrier, owing to potential limitations of the tissue in repair. Filling conductive guiding cues into nerve conduits has been effective in stimulating functional nerve recovery. The present study presents a novel porous conductive chitosan/polydopamine (CS/PDA) microcarriers for nerve defect repair were prepared by the self-polymerization properties of mussel-like macromolecule dopamine. The porosity is more than 90%, and the electrical conductivity reaches 7 × 10 −4 S/cm. The electrical signal was simulated by electrical stimulation in vitro . Compared with non-conductive microcarriers, conductive ones can effectively promote cell adhesion and proliferation. The conductive microcarriers loaded rat adipose-derived stem cells (rADSCs) were injected into nerve conduits and then transplanted into SD rats, with the autologous and the hollow groups as controls. The results of histology, immunohistochemical staining and gait analysis showed that CS/PDA had a promising ability to repair nerve defects in vivo .
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DOI
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Dongfang Hu,Bin Zhang,Yu Suo,Zhiyue Li,Zhishuai Wan,Weihua Zhao,Lingli Chen,Zhihong Yin,Hongmei Ning,Yaming Ge,Weiguo Li
Florfenicol (FLO), which is widely used in veterinary clinics and aquaculture, can disrupt the protein synthesis of bacteria and mitochondria and, thus, lead to antibacterial and toxic effects in plants, insects, and mammals. FLO was found to repress chicken embryonic development and induce early embryonic death previously, but the underlying mechanism is not fully understood. Clarifying the mechanism of FLO-induced embryonic toxicity is important to the research and development of new drugs and the rational use of FLO to ensure human and animal health and ecological safety. In this study, the effects of FLO on pluripotency, proliferation, and differentiation were investigated in P19 stem cells (P19SCs). We also identified differentially expressed genes and performed bioinformatics analysis to obtain hub genes and conducted some functional analysis. FLO inhibited the proliferation and pluripotency of P19SCs and repressed the formation of embryoid bodies derived from P19SCs. A total of 2,396 DEGs were identified using RNA-Seq in FLO-treated P19SCs, and these genes were significantly enriched in biological processes, such as angiogenesis, embryonic organ development, and morphogenesis of organs. Kyoto encyclopedia of genes and genome-based pathway analysis also showed that five relevant pathways, especially the canonical Wnt pathway, were engaged in FLO-induced toxicity of pluripotent stem cells. We further analyzed modules and hub genes and found the involvement of ubiquitin-mediated proteolysis, DNA replication, and cell cycle machinery in regulating the pluripotency and proliferation of FLO-treated P19SCs. In summary, our data suggest that FLO disrupts the signaling transduction of pathways, especially the canonical Wnt pathway, and further inhibits the expression of target genes involved in regulating DNA replication, cell cycle, and pluripotency. This phenomenon leads to the inhibition of proliferation and differentiation in FLO-treated P19SCs. However, further experiments are required to validate our findings and elucidate the potential mechanisms underlying FLO-induced embryonic toxicity.
研究领域:
药理学
·
干细胞生物学
·
毒理学
·
分子生物学
·
生物信息学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Xupeng Mu,Jing Li,Shaohua Yan,Hongmei Zhang,Wenjing Zhang,Fuqiang Zhang,Jinlan Jiang
Biomimetic cell membrane coated nanoparticles (NPs) with desirable features have been extensively applied for various personalized biomedicine. However, there have not been relative explorations by employing the membrane nanocomplexes for small interfering RNA (siRNA) delivery. Herein, Fe3O4@PDA NPs with good photothermal capability were applied for efficient siRNA loading and delivery, which were then coated by mesenchymal stem cells (MSCs) to form a membrane. The data showed that MSCs membrane coated Fe3O4@PDA–siRNA NPs (Fe3O4@PDA–siRNA@MSCs) maintained the photothermal functionality and the capability of magnetic resonance imaging inherited from Fe3O4@PDA. The synthesized nanocomplexes exhibited excellent abilities in the delivery of siRNA into DU145 cells. Furthermore, Fe3O4@PDA–siRNA@MSCs NPs delivering siRNA against Plk1 gene could inhibit the expression of endogenous Plk1 gene and cause obvious apoptosis in DU145 cells. The synergistic combination of photothermal treatment and gene silencing showed obvious antitumor efficacy in a DU145 xenograft mice model. On the basis of preliminary in vitro and in vivo studies, Fe3O4@PDA–siRNA@MSCs NPs hold considerable promise as a carrier for gene and photothermal therapy.
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Chen Anbin,Kristiansen Cecilie Katrin,Hong Yu,Kianian Atefeh,Fang Evandro Fei,Sullivan Gareth John,Wang Jian,Li Xingang,Bindoff Laurence A.,Liang Kristina Xiao
Mitophagy specifically recognizes and removes damaged or superfluous mitochondria to maintain mitochondrial homeostasis and proper neuronal function. Defective mitophagy and the resulting accumulation of damaged mitochondria occur in several neurodegenerative diseases. Previously, we showed mitochondrial dysfunction in astrocytes with POLG mutations, and here, we examined how POLG mutations affect mitophagy in astrocytes and how this can be ameliorated pharmacologically. Using induced pluripotent stem cell (iPSC)-derived astrocytes carrying POLG mutations, we found downregulation of mitophagy/autophagy-related genes using RNA sequencing-based KEGG metabolic pathway analysis. We confirmed a deficit in mitochondrial autophagosome formation under exogenous stress conditions and downregulation of the mitophagy receptor p62, reduced lipidation of LC3B-II, and decreased expression of lysosome protein lysosomal-associated membrane protein 2A (LAMP2A). These changes were regulated by the PINK1/Parkin pathway and AKT/mTOR/AMPK/ULK1 signaling pathways. Importantly, we found that double treatment with nicotinamide riboside (NR) and metformin rescued mitophagy defects and mitochondrial dysfunction in POLG-mutant astrocytes. Our findings reveal that impaired mitophagy is involved in the observed mitochondrial dysfunction caused by POLG mutations in astrocytes, potentially contributing to the phenotype in POLG-related diseases. This study also demonstrates the therapeutic potential of NR and metformin in these incurable mitochondrial diseases.
研究领域:
神经科学
·
细胞生物学
·
分子生物学
·
干细胞研究
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2023
·
IF 4.8
Liqun Chen,Wei Fang,Weizhi Chen,Yiliu Wei,Jinwang Ding,Jiafeng Li,Jun Lin,Qiaoyi Wu
Glioma stem cells (GSCs) are thought to be responsible for the initiation and progression of glioblastoma (GBM). GBM presents highly invasive growth with a very high recurrence rate, so it has become a clinical problem to be solved urgently. RNAseq demonstrates that thrombospondin 1 (THBS1) acts not only in the angiogenic core of glioma but also with a high degree of invasiveness and infiltration. Nevertheless, defects in the signaling pathway research lead to a poor prognosis in glioma patients. To investigate the relevant molecular mechanism and signal pathway of glioma stem cell behavior mediated by THBS1 , U251 astroglioma cells and GSCs were taken as model cells for in vitro experiments. The biological effects of THBS1 on glioma proliferation, migration, and adhesion were evaluated using Cell Counting Kit-8(CCK8) assays, EdU incorporation assays, migration assays, Transwell assays, Western blotting , and RNAseq. We found that the knockout of the THBS1 gene by CRISPR/Cas9 promoted proliferation and migration in U251 cells and GSCs, as well as influencing cell cycle progression by regulating the TNF/MAPK/NF-κB and TGF-β/Smad signaling pathways. Moreover, U251 cells and GSCs showed different responses to THBS1 knockout, suggesting specific and potential targets for GSCs in signaling pathways mediated by THBS1 .
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
癌症研究
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DOI
PubMed
高影响因子
Stem Cells International
·
2020
·
IF 3.869
Kang Lu,Xiaodie Chen,Hong Tang,Mei Zhou,Gang He,Zhisong Lu,Kanglai Tang
Background. Tendon injuries are common musculoskeletal disorders in clinic. Due to the limited regeneration ability of tendons, tissue engineering technology is often used as an effective approach to treat tendon injuries. Silk fibroin (SF) films have excellent biological activities and physical properties, which is suitable for tendon regeneration. The present study is aimed at preparing a SF film with a bionic microstructure and investigating its biological effects. Methods. A SF film with a smooth surface or bionic microstructure was prepared. After seeding tendon stem/progenitor cells (TSPCs) on the surface, the cell morphology, the expression level of tenogenic genes and proteins, and the focal adhesion kinase (FAK) activation were measured to evaluate the biological effect of SF films. Results. The TSPCs on SF films with a bionic microstructure exhibited a slender cell morphology, promoted the expression of tenogenic genes and proteins, such as SCX, TNC, TNMD, and COLIA1, and activated FAK. FAK inhibitors blocked the enhanced expression of tenogenic genes and proteins. Conclusion. SF films with a bionic microstructure may serve as a scaffold, provide biophysical cues to alter the cellular adherence arrangement and cell morphology, and enhance the tenogenic gene and protein expression in TSPCs. FAK activation plays a key role during this biological response process.
研究领域:
生物医学工程
·
再生医学
·
细胞生物学
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DOI
PubMed
高影响因子
Stem Cells International
·
2019
·
IF 3.902
Si Wu,Yachuan Zhou,Yi Yu,Xin Zhou,Wei Du,Mian Wan,Yi Fan,Xuedong Zhou,Xin Xu,Liwei Zheng
The pulpotomy with pulp capping is aimed at retaining vital pulp with reparative dentin formation. Vascular endothelial growth factor (VEGF) plays a crucial role in dentin regeneration; however, its constant administrations in the human body is still problematic. Chitosan was widely studied as an effective carrier to deliver bioactive molecules in regenerative medicine. In this study, we conducted a chitosan/β-glycerophosphate (CS/β-GP) hydrogel as a VEGF-sustained release system and explored its effects on dental pulp stem cells (DPSCs). CS/β-GP hydrogel was manufactured using a sol-gel method. SEM assay showed the spongy and porous microstructure of the lyophilized hydrogels. DPSCs cultured in the CS/β-GP hydrogel kept adhesion and vitality. CCK-8 assay tested the promoted proliferation activity of DPSCs on the hydrogel. Besides, the added VEGF protein could continually release from VEGF/CS/β-GP hydrogel. The VEGF/CS/β-GP hydrogel could promote the odontogenic differentiation of DPSCs better than VEGF treatment without hydrogel. Our results suggested that CS/β-GP hydrogel could continually release VEGF and contribute to odontogenic differentiation of DPSCs, thus may become a potential carrier of bioactive molecules in pulp capping therapy.
研究领域:
再生医学
·
牙科材料
·
干细胞生物学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2023
·Vol. 18
·期 1
·1-12
·
IF 2.6
Su Hairong,Yang Yulan,Lv Wanchun,Li Xiaoli,Zhao Binxiu
Background Osteoporosis (OP) is a systemic skeletal disorder with increased bone fragility. Human bone marrow mesenchymal stem cells (hBMSCs) have multi-lineage differentiation ability, which may play important roles in osteoporosis. In this study, we aim to investigate the role of hBMSC-derived miR-382 in osteogenic differentiation.Methods The miRNA and mRNA expressions in peripheral blood monocytes between persons with high or low bone mineral density (BMD) were compared. Then we collected the hBMSC-secreted sEV and examined the dominant components. The over-expression of the miR-382 in MG63 cell and its progression of osteogenic differentiation were investigated by qRT-PCR, western blot and alizarin red staining. The interaction between miR-382 and SLIT2 was confirmed by dual-luciferase assay. The role of SLIT2 was also confirmed through up-regulation in MG63 cell, and the osteogenic differentiation-associated gene and protein were tested.Results According to bioinformatic analysis, a series of differential expressed genes between persons with high or low BMD were compared. After internalization of hBMSC-sEV in MG63 cells, we observed that the ability of osteogenic differentiation was significantly enhanced. Similarly, after up-regulation of miR-382 in MG63 cells, osteogenic differentiation was also promoted. According to the dual-luciferase assay, the targeting function of miR-382 in SLIT2 was demonstrated. Moreover, the benefits of hBMSC-sEV in osteogenesis were abrogated through up-regulation of SLIT2.Conclusion Our study provided evidence that miR-382-contained hBMSC-sEV held great promise in osteogenic differentiation in MG63 cells after internalization by targeting SLIT2, which can be served as molecular targets to develop effective therapy.
研究领域:
干细胞生物学
·
分子生物学
·
骨骼生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
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