Stem Cells International
·
2022
·
IF 5.131
Yuan Luo,Xiaodong Cao,Junfeng Chen,Jianwei Gu,Hao Yu,Junying Sun,Jun Zou
Cartilage regeneration is still a challenge for clinicians because of avascularity, denervation, load-bearing, synovial movement, and the paucity of endogenous repair cells. We constructed a multilayered osteochondral bionic scaffold and examined its repair capacity using a rabbit osteochondral defect model. The cartilage phase and interface layer of the scaffold were prepared by freeze-drying, whereas the bone phase of the scaffold was prepared by high-temperature sintering. The three-phase osteochondral bionic scaffold was formed by joining the hydroxyapatite (HAp) and silk fibroin (SF) scaffolds using the repeated freeze-thaw method. Different groups of scaffolds were implanted into the rabbit osteochondral defect model, and their repair capacities were assessed using imaging and histological analyses. The cartilage phase and the interface layer of the scaffold had a pore size of and , respectively. All generated scaffolds exhibited a honeycomb porous structure. The polydopamine- (PDA-) modified scaffold released platelet-derived growth factor (PDGF) for 4 weeks continuously, reaching a cumulative release of . Synovial mesenchymal stem cells (SMSCs) adhered well to all scaffolds, but demonstrated the strongest proliferation ability in the HSPP (HAp-Silk-PDA-PDGF) group. Following scaffold-induced chondrogenic differentiation, SMSCs produced much chondrocyte extracellular matrix (ECM). In in vivo experiments, the HSPP group exhibited a significantly higher gross tissue morphology score and achieved cartilage regeneration at an earlier stage and a significantly better repair process compared with the other groups (). Histological analysis revealed that the new cartilage tissue in the experimental group had a better shape and almost filled the defect area, whereas the scaffold was nearly completely degraded. The new cartilage was effectively fused with the surrounding normal cartilage, and a substantial amount of chondrocyte ECM was formed. The SF/HAp three-layer osteochondral bionic scaffold exhibited favorable pore size, porosity, and drug sustained-release properties. It demonstrated good biocompatibility in vitro and encouraging repair effect at osteochondral defect site in vivo, thereby expected to enabling the repair and regeneration of osteochondral damage.
研究领域:
再生医学
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组织工程
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生物材料学
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DOI
PubMed
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
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干细胞生物学
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毒理学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
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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
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细胞生物学
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分子生物学
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干细胞研究
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药理学
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2023
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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
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
Stem Cells International
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2020
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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
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再生医学
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细胞生物学
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DOI
PubMed
高影响因子
Stem Cells International
·
2019
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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
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牙科材料
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干细胞生物学
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组织工程
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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
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分子生物学
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骨骼生物学
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再生医学
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DOI
PubMed
高影响因子
eLife
·
2019
·
IF 7.551
Xuefei Yan,Beibei Tang,Biao Chen,Yongli Shan,Huajun Yang,Reproducibility Project: Cancer Biology,Elizabeth Iorns,Rachel Tsui,Alexandria Denis,Nicole Perfito,Timothy M Errington
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Haopeng Lin,Xin Liu,Feng Zhang,Deqi Chen,Xiaoxiao Xie,Qifei Dong,Jiawei Yan,Jiaxiang Yin,Zirong Bi,Zhihua Dou,Yingling Jiang,Kuo Jiang,Tongran Zhang,Peng Xue,Wei Peng,Lihua Chen,Tao Xu,Zonghong Li,Yanying Guo,Huisheng Liu
Human stem cell-derived β (SC-β) cells still exhibit limited glucose response required for insulin secretion due to glycolytic bottlenecks, yet how these metabolic abnormalities impact glucose response and functional maturation of SC-β cells remains unclear. In this study, we identify a metabolic checkpoint located at PEP accumulation that impedes the functional maturation, which is rescued by restoration of pyruvate kinase M1 ( PKM1 ). Glucose-tracing metabolomics in human stem cell-derived islets reveal abnormal glycolytic PEP accumulation at resting condition, associated with impaired calcium response and insulin secretion upon high glucose or glycolytic metabolite stimulation. Mechanistically, elevated PEP significantly raises intracellular basal calcium levels and downregulates expression of genes involved in TCA cycle as elucidated by single cell transcriptomics. Furthermore, the activity of pyruvate kinase, which metabolizes PEP, is notably reduced due to low PKM1 expression. Overexpression of PKM1 alleviates PEP accumulation, restores TCA-related gene expression, and enhances glucose-stimulated calcium responses and insulin secretion. Together, our findings reveal a critical role of PKM1-regulated PEP metabolism in SC-β cell functional maturation and highlight the importance of metabolic reprogramming for advancing stem cell-based therapies for diabetes. Human stem cell–derived β cells accumulate high basal PEP, which disrupts glucose-stimulated insulin release. Restoring PKM1 lowers basal PEP and improves glucose responses, advancing the maturation of stem cell–derived islets for diabetes therapy.
研究领域:
糖尿病研究
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干细胞生物学
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代谢学
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再生医学
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细胞生理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Yaqing Liu,Duo Xu,Ying Dong,Canghai An,Zikun Jia,Tianci Wang,Ling Su
The stem of Tremella fuciformis , an abundant byproduct of edible mushroom processing, is typically discarded despite containing higher levels of crude polysaccharide than the fruiting body. To valorize this agricultural residue, a series of polysaccharide-based hydrogels was fabricated via Schiff base crosslinking between carboxymethyl chitosan (CMCS) and oxidized T. fuciformis stem polysaccharide (OTP) with tunable aldehyde contents. The oxidation degree of OTP critically influenced the crosslinking density, thereby modulating the gelation kinetics, microstructure, rheological properties, and swelling behavior. Specifically, increasing the polysaccharide oxidation degree from 17.30 ± 1.66% to 32.85 ± 1.47% and subsequently to 40.75 ± 1.96% progressively shortened the gelation time from 12 min to 3 min and decreased the pore size from 219.2 ± 12.50 μm to 93.16 ± 16.60 μm. Concurrently, the storage modulus increased from 49 Pa to 388 Pa, and the CMOT3 hydrogel achieved the highest equilibrium swelling rate of 99.6%. All hydrogel formulations exhibited excellent cytocompatibility. In a full-thickness skin defect model, the optimally crosslinked CMOT3 hydrogel significantly accelerated wound closure, which was associated with reduced pro-inflammatory cytokine levels, elevated VEGF expression, and improved collagen organization. These findings suggest that the T. fuciformis stem polysaccharide-based hydrogel effectively promotes skin tissue repair, highlighting its potential as a sustainable functional biomaterial derived from agricultural byproducts.
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产品关联
DOI
高影响因子
Frontiers in Bioscience-Landmark
·
2026
·Vol. 31
·期 8
·
IF 4.1
Yulian Shi,Tingyu Fan,Rongmei Qu,Guosheng Wu,Xiangtian Li,Jiaxuan Liu,Ziyi Feng,Haopeng Wu,Jun Ouyang,Jingxing Dai
Background:
Bone tissue possesses strong regenerative potential, but large segmental bone defects often exceed its intrinsic capacity for self-healing. Human adipose-derived stem cells (hASCs) offer a promising cellular basis for bone regeneration owing to their robust osteogenic differentiation potential. However, the role of PDZ and LIM domain 2 (PDLIM2) play in hASC osteogenesis and its relationship with the Wnt/β-catenin signaling pathway remain poorly understood.
Methods:
Western blotting, immunofluorescence staining, Alizarin Red S staining, alkaline phosphatase activity assays, wound healing assays, and Transwell assays were employed to assess osteogenic differentiation, osteogenic capacity, and cellular migration. Lentivirus-mediated PDLIM2 knockdown, cytochalasin D (CytoD) intervention, microfilament stabilizer treatment, and β-catenin activator treatment were used as a means of validating the regulatory mechanism.
Results:
hASCs exhibited the ability to undergo osteogenic differentiation. During this osteogenic process, significant increases in PDLIM2, β-actin, and β-catenin expression were observed, with PDLIM2 expression reaching 2–3 times that of the control group on day 14, whereas β-actin and β-catenin levels peaked on day 7 (1.5–2 times those in the control group). Lentivirus-mediated PDLIM2 knockdown reduced β-actin expression by approximately 5-fold and β-catenin expression by approximately 1.7-fold, accompanied by cytoskeletal disorganization and impaired osteogenic differentiation. Actin microfilament integrity was found to regulate osteogenic marker expression and alkaline phosphatase activity, while CytoD treatment suppressed β-actin and β-catenin expression to approximately 50% of control levels and inhibited osteogenic differentiation. Knocking down PDLIM2 attenuated the responsiveness of hASCs to microfilament stabilizers and β-catenin activators.
Conclusions:
This study demonstrates that PDLIM2 may be functionally associated with β-catenin nuclear translocation, potentially through the remodeling of the actin cytoskeleton. These findings provide preliminary mechanistic insight and warrant further validation.
Keywords
PDLIM2human adipose-derived stem cells (hASCs)osteogenesiscytoskeletonβ-catenin
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产品关联
DOI
高影响因子
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