Oxidative Medicine and Cellular Longevity
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2022
·
IF 7.31
Yang Yang,Bo Zhang,Yufan Yang,Bibo Peng,Rui Ye
Calcitonin gene-related peptide (CGRP) is an important neuropeptide expressed in the nerve fibers during bone repair. Here, we aimed to pinpoint the role of CGRP in the osteogenic differentiation property of human periodontal ligament stem cells (hPDLSCs) and the resultant repair of alveolar bone defect. The key factor related to the osteogenic differentiation of hPDLSCs was retrieved from the GEO database. After extraction from hADSCs (hADSC-EVs) and identification, EVs were subjected to coculture with hPDLSCs, in which the expression patterns of CGRP and osteogenic differentiation marker proteins (ALP, RUNX2, and OCN), as well as ALP activity, were detected. A novel cell-free tissue-engineered bone (TEB) comprised of PLGA/pDA and hADSC-EVs was implanted into the rats with alveolar bone defects to evaluate the repair of alveolar bone defects. CGRP was enriched in hADSC-EVs. hADSCs delivered CGRP to hPDLSCs through EVs, thereby promoting the osteogenic differentiation potential of hPDLSCs. The PLGA/pDA-EV scaffold released EVs slowly, and its implantation into the rat alveolar bone defect area significantly induced bone defect repair, which was reversed by further knockdown of CGRP. In conclusion, our newly discovered cell-free system consisted of hADSC-EVs, and PLGA/pDA scaffold shows promising function in repairing alveolar bone defects.
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高影响因子
Frontiers in Cell and Developmental Biology
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2021
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IF 6.684
Wang Yichao,Wang Pan,Zhao Lei,Chen Xiaoying,Lin Zhu,Zhang Ling,Li Zhaoyun
Objective: In this study, we focused on the potential mechanism of miRNAs carried by human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-exo) in breast cancer (BC).Methods: RT-qPCR was conducted for the expression of miR-224-5p and HOXA5 in tissues and cells. After co-culture of exosomes and MCF-7 or MDA-MB-231 cells, the cell proliferation was observed by MTT and cell colony formation assay, while apoptosis was measured by flow cytometry. In addition, the expression of HOXA5 and autophagy pathway-related proteins LC3-II, Beclin-1 and P62 was detected by western blotting. And immunofluorescence was applied for detection of LC3 spots. The binding of miR-224-5p to HOXA5 was verified by the luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. Finally, in vivo experiment was performed to investigate the effect of miR-224-5p on BC growth.Results: MiR-224-5p was up-regulated and HOXA5 was down-regulated in BC tissues and cells. HOXA5 was confirmed to be the target gene of miR-224-5p. MiR-224-5p carried by hUCMSCs-exo was able to promote the proliferation and autophagy of BC cells, while inhibited apoptosis. Bases on xenograft models in nude mice, it was also revealed that miR-224-5p carried by hUCMSCs-exo could regulate autophagy and contribute to the occurrence and development of BC in vivo.Conclusion: MiR-224-5p carried by hUCMSCs-exo can regulate autophagy via inhibition of HOXA5, thus affecting the proliferation and apoptosis of BC cells.
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高影响因子
EXPERIMENTAL CELL RESEARCH
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2021
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IF 3.905
Yiming Li,Yi He,Guanhui Chen,Ziqing Huang,Chen Yi,Xiliu Zhang,Feilong Deng,Dongsheng Yu
abstract Dental implant surgery is currently a routine therapy for the repair of missing dentition or dentition defects. Both clinical and basic research have elucidated that oxidative stress caused by the accumulation of reactive oxygen species (ROS) for various reasons impairs the process of osteointegration after dental implantation. Therefore, the osteogenic micro-environment must be ameliorated to decrease the damage caused by oxidative stress. Selenomethionine (SEMET) has been reported to play an important role in alleviating oxidative stress and accelerating cell viability and growth. However, it remains unclear whether it exerts protective effects on bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. In this study, we explored the influence of selenomethionine on the viability and osteogenic differentiation of BMSCs under oxidative stress and the underlying mechanisms. Results showed that 1 μM selenomethionine was the optimum concentration for BMSCs under H 2 O 2 stimulation. H 2 O 2 -induced oxidative stress suppressed the viability and osteogenic differentiation of BMSCs, manifested by the increases in ROS production and cell apoptosis rates , and by the decrease of osteogenic differentiation-related markers. Notably, the aforementioned oxidative damage and osteogenic dysfunction induced by H 2 O 2 were rescued by selenomethionine. Furthermore, we found that the PTEN expression level was suppressed and its downstream PI3K/AKT pathway was activated by selenomethionine. However, when PTEN was stimulated, the PI3K/AKT pathway was down-regulated, and the protective effects of selenomethionine on BMSC osteogenic differentiation diminished, while the inhibition of PTEN up-regulated the protective effects of selenomethionine. Together, these results revealed that selenomethionine could attenuate H 2 O 2 -induced BMSC dysfunction through an antioxidant effect, modulated via the PTEN/PI3K/AKT pathway, suggesting that selenomethionine is a promising antioxidant candidate for reducing oxidative stress during the process of dental implant osteointegration.
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高影响因子
Advanced Healthcare Materials
·
2020
·Vol. 9
·期 11
·1901570
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IF 7.367
Xiaofang Hu,Xianghai Wang,Yizhou Xu,Lixia Li,Jingmin Liu,Yutong He,Ying Zou,Lei Yu,Xiaozhong Qiu,Jiasong Guo
Schwann cells (SCs) are the most promising seed cells for peripheral nerve tissue engineering, but clinical applications are limited by the lack of cell sources. Existing data demonstrate that bone marrow mesenchymal stem cells (BMSCs) can be induced to differentiate into Schwann-like cells and aligned nanofibers can enhance the differentiation. Considering that SCs are living along with the electrical conductive axons, it is hypothesized that conductivity properties may play roles in SCs differentiation and then facilitate nerve regeneration. To verify this hypothesis, amine functionalized multi-walled carbon nanotubes (MWCNTs) are incorporated with polycaprolactone and gelatin to fabricate aligned or random conductive nanofibers by electrospinning. Current data demonstrate that MWCNTs can dramatically increase the electrical conductive properties but do not alter the biocompatibility of the nanofibers. It is found that endowing conductive properties into the aligned nanofibers can significantly enhance their capability to promote the SCs differentiation. Furthermore, the aligned and conductive nanofibers with induced BMSCs can dramatically promote peripheral axonal regeneration. Collectively, the present study demonstrates that the conductive properties in the aligned nanofiber plays significant roles in SCs differentiation and the aligned and conductive nanofibers can be used as a promising scaffold for SCs differentiation and peripheral nerve tissue engineering.
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高影响因子
Acta Biomaterialia
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2013
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IF 5.093
Y. Deng,X. Zhang,X. Zhao,Q. Li,Z. Ye,Z. Li,Y. Liu,Y. Zhou,H. Ma,G. Pan,D. Pei,J. Fang,S. Wei
Realization of the full potential of human induced pluripotent stem cells (hiPSC) in clinical applications requires the development of well-defined culture conditions for their long-term growth and directed differentiation. This paper describes a novel fully defined synthetic peptide-decorated substrate that supports self-renewal of hiPSC in commercially available xeno-free, chemically defined medium. The Au surface was deposited by a poly(OEGMA- co -HEMA) film, using the surface-initiated polymerization method (SIP) with the further step of carboxylation . The hiPSC generated from umbilical cord mesenchymal cells were successfully cultured for 10 passages on the peptide-tethered poly(OEGMA- co -HEMA) brushes for the first time. Cells maintained their characteristic morphology, proliferation and expressed high levels of markers of pluripotency, similar to the cells cultured on Matrigel™. Moreover, the cell adhesion could be tuned by the pattern and peptide concentration on the substrate. This well-defined, xeno-free and safe substrate, which supports long-term proliferation and self-renewal of hiPSC, will not only help to accelerate the translational perspectives of hiPSC, but also provide a platform to elucidate the underlying molecular mechanisms that regulate stem cell proliferation and differentiation via SIP technology.
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高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Jinze Li,Jiali Zhang,Hao Ye,Qixuan Wang,Yanran Ouyang,Yuxi Luo,Yihong Gong
Introduction: Mesenchymal stem cells (MSCs) possess a high degree of self-renewal capacity and in vitro multi-lineage differentiation potential. Decellularized materials have garnered considerable attention due to their elevated biocompatibility, reduced immunogenicity, excellent biodegradability, and the ability to partially mimic the in vivo microenvironment conducive to cell growth. To address the issue of mesenchymal stem cells losing their stem cell characteristics during two-dimensional (2D) cultivation, this study established three-dimensional cell carriers modified with lung decellularized extracellular matrix and assessed its impact on the life activities of mesenchymal stem cells. Methods: This study employed PET as a substrate material, grafting with polydopamine (PDA), and constructing a decellularized extracellular matrix (dECM) coating on its surface, thus creating the PET/PDA/dECM three-dimensional (3D) composite carrier. Subsequently, material characterization of the cellular carriers was conducted, followed by co-culturing with human umbilical cord mesenchymal stem cells in vitro , aiming to investigate the material’s impact on the proliferation and paracrine activity of mesenchymal stem cells. Results and Discussion: Material characterization demonstrated successful grafting of PDA and dECM materials, and it had complete hydrophilicity, high porosity, and excellent mechanical properties. The material was rich in various ECM proteins (collagen I, collagen IV , laminin, fibronectin, elastin), indicating good biocompatibility. In long-term in vitro cultivation (14 days) experiments, the PET/PDA/dECM three-dimensional composite carrier significantly enhanced adhesion and proliferation of human umbilical cord-derived mesenchymal stem cells (HUCMSCs), with a proliferation rate 1.9 times higher than that of cells cultured on tissue culture polystyrene (TCPS) at day 14. Furthermore, it effectively maintained the stem cell characteristics, expressing specific antigens for HUCMSCs. Through qPCR, Western blot, and ELISA experiments, the composite carrier markedly promoted the expression and secretion of key cell factors in HUCMSCs. These results demonstrate that the PET/PDA/dECM composite carrier holds great potential for scaling up MSCs’ long-term in vitro cultivation and the production of paracrine factors.
研究领域:
组织工程
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干细胞生物学
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生物材料
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细胞治疗
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高影响因子
Cell Regeneration
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2020
·Vol. 9
·期 1
·1-16
·
IF 0
Guo Anqi,Wang Bingjie,Lyu Cheng,Li Wenjing,Wu Yaozu,Zhu Lu,Bi Ran,Huang Chenyu,Li Jiao Jiao,Du Yanan
Apparent Young’s modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established.Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types. Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics. On substrates that were too rigid or too soft, fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity. On a substrate with ‘optimal’ stiffness (i.e., 3.5 kPa), the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity. The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP.In summary, this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.
研究领域:
干细胞生物学
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生物物理学
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再生医学
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DOI
PubMed
Molecular Therapy-Methods & Clinical Development
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2023
·
IF 4.7
Jiaqi Zeng,Jianing Liu,Haiya Ni,Ling Zhang,Jun Wang,Yazhou Li,Wentao Jiang,Ziyu Wu,Min Zhou
Recent studies have shown that mitochondrial transplantation can repair lower limb IRI, but the underlying mechanism of the repair effect remains unclear. In this study, we found that in addition to being taken up by skeletal muscle cells, human umbilical cord mesenchymal stem cells (hMSCs)-derived mitochondria were also taken up by adipocytes, which was accompanied by an increase in optic atrophy 1 (OPA1) and uncoupling protein 1. Transplantation of hMSCs-derived mitochondria could not only supplement the original damaged mitochondrial function of skeletal muscle, but also promote adipocyte browning by increasing the expression of OPA1. In this process, mitochondrial transplantation can reduce cell apoptosis and repair muscle tissue, which promotes the recovery of motor function in vivo . To the best of our knowledge, there is no study on the therapeutic mechanism of mitochondrial transplantation from this perspective, which could provide a theoretical basis.
研究领域:
医学
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细胞生物学
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Tissue Engineering and Regenerative Medicine
·
2026
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IF 5.1
Ma Shengqin,Qin Liying,Wang Shaodong,Meng Ting,Zhao Zhengyan,Liu Maoying,Zhang Chuan,Wu Fang,Zhou Ping
BACKGROUND : Human pluripotent stem cells (hPSCs) offer vast potential for cellular therapies due to their unique abilities in self-renewal and differentiation. However, the reliance on animal-derived Matrigel in conventional cell culture limits clinical translation, and developing chemically defined synthetic surfaces remains a key technical challenge.
METHODS : Based on our previously established synthetic polydopamine-based peptide-displaying surfaces, this study systematically optimized each fabrication step, including substrate selection, raw material screening (dopamine, carboxymethyl chitosan), reaction conditions, post-conjugation medium blocking, and peptide-dissolving buffer systems. Molecular docking was performed to analyze peptide-integrin αVβ5 interactions, and findings were verified using alginate-gelatin hydrogel and Maleylated-BSA coatings.
RESULTS:
Compared with commercial plates, pure polystyrene plates showed better abilities in sustaining cell culture, and the optimal raw materials for dopamine and carboxymethyl chitosan as well as their ideal reaction conditions were identified. Interestingly, not only does medium blocking after peptide conjugation play a crucial role, but the use of alkaline peptide-dissolving buffers also provides a significant advantage in supporting hPSCs adhesion and self-renewal. Molecular docking revealed enhanced peptide-integrin αVβ5 binding energetics under alkaline conditions. The optimized peptide-displaying surface demonstrated superior performance in supporting hPSCs culture and differentiation.
CONCLUSION:
Our study reveals several previously unknown critical factors in the preparation of synthetic peptide-displaying surfaces. The optimized protocol improves hPSC culture performance and provides a reliable foundation for advancing chemically defined, animal component-free coatings toward commercial and clinical applications.
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高影响因子
Scientific Reports
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2026
·
IF 4.9
Shi Minke,Wang Jiarui,Guo Qihan,Wang Jiayu,Sarengaowa,Ji Yaru,Xiao Ying,Feng Ke
Stem lettuce is a nutritious vegetable rich in dietary fiber, vitamins, and bioactive compounds, but fresh-cut processing accelerates browning, oxidative stress, and quality deterioration during storage. This study investigated the effects of ethanol vapor on browning inhibition, antioxidant capacity, and reactive oxygen species (ROS) metabolism in fresh-cut stem lettuce. Samples were treated with ethanol vapor at 0, 0.5, 1.0, and 2.0 mL/L and stored for 12 days. Among the treatments, 0.5 mL/L ethanol vapor most effectively delayed browning by suppressing the activities of peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase, while reducing the accumulation of superoxide anion radicals and hydrogen peroxide. This treatment also enhanced antioxidant defense systems by increasing the activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, as well as non-enzymatic antioxidant capacity, as indicated by elevated FRAP, DPPH, and ABTS scavenging activities. By the end of storage, FRAP and DPPH values in the 0.5 mL/L group were approximately 1.8 and 2-fold higher than those of the control. Overall, ethanol vapor at 0.5 mL/L effectively alleviated oxidative stress, maintained ROS homeostasis, and delayed enzymatic browning, demonstrating its potential as a practical preservation strategy to improve postharvest quality and extend the shelf life of fresh-cut stem lettuce during cold storage.
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高影响因子
American Journal of Translational Research
·
2023
·
IF 2.2
Ying Li,Lu Cheng,Qian Xia,Maohua Meng,Qinying Wang,Xiao Zeng,Yuanyuan Jia,Chunying Liu,Lei Wu,Helin Chen,Qiang Dong
Objective: To explore the potential osteogenic induction mechanism of enamel matrix derivatives (EMDs) on bone marrow mesenchymal stem cell (BMSC) sheets with different titanium surface morphologies. Methods: The BMSCs were inoculated on the surfaces of titanium alloys with different morphologies: anodic oxidation (AO), sand-blasted, large grit and acid-etched, and no treatment (control). The proliferation and osteogenic differentiation of BMSCs on the different surface morphologies were observed with the same concentration of EMDs. To further understand the osteogenic mechanism of EMDs on BMSC sheets with different morphologies, a real-time RT-PCR and a western blot were used to detect the overall levels of osteogenic genes and osteogenic proteins. Finally, to verify the osteogenic effect of BMSC sheets stimulated by EMDs in vivo, BMSC sheets with different morphologies were implanted into the subcutaneous tissue of the back of nude mice, and the bone formation was detected by HE staining. Results: The EMDs and surface morphology in the AO group synergically increased the expression levels of osteogenic active factors (RUNX2, OSX and OCN) and enhanced the osteogenic differentiation effect of BMSCs. The in vivo experiments showed that the BMSC sheets in the AO group were rich in osteogenic active factors, and promoted the formation of ectopic bone tissue after implantation into the subcutaneous tissue of the back of nude mice. Conclusion: EMDs and AO morphology synergically enhance the secretion of bone osteogenic active factors of BMSCs and promote the formation of heterotopic bone.
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PubMed
高影响因子
Journal of Future Foods
·
2025
·
IF 7.2
Yan-Yan Zheng,Ze-Nan Hu,Chao Huang,Nan-Jing Zhong,Guang-Hong Zhou
Cell cultured meat (CCM) has become a research hotspot in the field of meat substitutes because of its environmental friendliness. Improving the overall flavor of CCM and further enhancing consumer acceptance is the key to its entry into the market for sale. Therefore, this study aimed to develop differential medium with higher food safety for adipose precursor cells (APCs) and optimize the co-differentiation conditions of APCs and muscle stem cells (MuSCs) on this basis. Then, using co-differentiated APCs and MuSCs as 3D printed bioinks to produce CCM. The results of this study indicate that food grade soybean oil and l-Ascorbic acid 2-phosphate (Asc-2P) can significantly promote lipid droplet generation in APCs and shorten APCs differentiation time ( P <0.05). Simultaneous differentiation of MuSCs and APCs was achieved using a 7:3 inoculation ratio combined with optimization of the co-differentiation medium. And the 3D-printed CCM has a similar appearance to traditional meat and similar flavor profiles in volatile flavor substances such as alkanes, alcohols and aliphatic compounds. Ultimately, this study provides a theoretical support for the production of higher safety and better flavored CCM.
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高影响因子
危险品化学品经营许可证（带存储）