JOURNAL OF ENDODONTICS
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2019
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IF 2.833
Jing Zhang,Cheng Fei Zhang,Quan Li Li,Chun Hung Chu
Introduction Stem cells from the apical papilla (SCAPs) possess strong odonto/osteogenic differentiation potential. This study investigated the effect of cyclic adenosine monophosphate (cAMP) on odonto/osteogenic differentiation of SCAPs and the underlining interplay between cAMP and transforming growth factor beta 1 (TGF-β1). Methods SCAPs were stimulated with an activator of cAMP (forskolin) in the presence of either TGF-β1 or a TGF-β1 inhibitor. The amounts of calcium mineral deposition and alkaline phosphatase activity were determined. Quantitative real-time polymerase chain reaction was performed to elucidate cAMP on the TGF-β1–mediated odonto/osteogenic differentiation of SCAPs. The effect of cAMP on the phosphorylation of Smad2/Smad3 and extracellular-regulated kinase (ERK)/P38 induced by TGF-β1 was analyzed by Western blotting . Results Cotreatment with forskolin and a TGF-β1 inhibitor enhanced alkaline phosphatase activity and deposition of calcium minerals in SCAPs. Moreover, the TGF-β1 inhibitor synergized the effect of forskolin on the expression of type I collagen and runt-related transcription factor 2. The results of Western blotting revealed that forskolin attenuated the unregulated expression of the phosphorylation of Smad3 and ERK induced by TGF-β1, and a cAMP inhibitor (H89) antagonized this effect. Conclusions This study showed that cAMP signaling exerts its up-regulating effects on the odonto/osteogenic differentiation of SCAPs by interfering with TGF-β1 signaling via inhibiting Smad3 and ERK phosphorylation.
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JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2019
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IF 2.895
Yiming Li,Guanhui Chen,Yi He,Xiliu Zhang,Binghui Zeng,Chao Wang,Chen Yi,Dongsheng Yu
Background Patients with metabolic bone diseases often have high risk of titanium implant failure due to compromised bone regeneration ability. Clinical evidence indicates that the poor osteogenic ability is partly because of excessive oxidative stress. To date, specific treatments for these patients are urgently needed. Ebselen, a non-toxic organoselenium compound, is reported to be a potent antioxidant agent. In this study, we hypothesized that ebselen exerted protective effects on osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. Methods BMSCs were isolated from SD rats, and their morphology and multiple differentiation abilities were characterized. Proliferation rates of BMSCs treated with different concentrations of ebselen were analyzed. Then BMSCs were pretreated by hydrogen peroxide (H 2 O 2 ), after which ebselen at different concentrations (0, 1, 5, 10 μM) was added, alkaline phosphatase (ALP) activity, mineralization and osteogenic-related protein levels were evaluated and an optimum concentration of ebselen was selected. Subsequently, intracellular reactive oxygen species (ROS) generation and the role of the PI3K/AKT pathway were also investigated. Results Ebselen within a proper range could promote the proliferation of BMSCs. H 2 O 2 -induced oxidative stress suppressed osteogenic differentiation of BMSCs, which was verified by the decrease in ALP activity, calcium deposition, Runx2 and β-catenin expression. However, ebselen could alleviate osteogenic dysfunction of BMSCs. We also observed that ebselen reduced ROS accumulation in H 2 O 2 -pretreated BMSCs. Moreover, the pro-osteogenic effects afforded by ebselen were almost abolished by the Akt inhibitor. Conclusion We concluded that ebselen could attenuate osteogenic dysfunction of BMSCs induced by H 2 O 2 through an antioxidant effect and the activation of the PI3K/Akt pathway, suggesting that ebselen has a potential therapeutic effect for patients with metabolic bone diseases.
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Stem Cell Research & Therapy
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2019
·Vol. 10
·期 1
·1-11
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IF 4.627
Liao Naishun,Shi Yingjun,Zhang Cuilin,Zheng Youshi,Wang Yingchao,Zhao Bixing,Zeng Yongyi,Liu Xiaolong,Liu Jingfeng
Background Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising candidates for regenerative medicine. However, long-term in vitro passaging leads to stemness loss and cell senescence of ADSCs, resulting in failure of ADSC-based therapy. Methods In this study, ADSCs were treated with low dose of antioxidants (reduced glutathione and melatonin) with anti-aging and stem cell protection properties in the in vitro passaging, and the cell functions including stem cell senescence, cell migration, cell multidirectional differentiation potential, and ROS content were carefully analyzed. Results We found that GSH and melatonin could maintain ADSC cell functions through reducing cell senescence and promoting cell migration, as well as by preserving stemness and multidirectional differentiation potential, through inhibiting ROS generation during long-term expansion of ADSCs. Conclusions Our results suggested that antioxidant treatment could efficiently prevent the dysfunction and preserve cell functions of ADSCs after long-term passaging, providing a practical strategy to facilitate ADSC-based therapy.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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2018
·Vol. 46
·期 4
·389-397
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IF 2.092
Hao Yuan,Hongyan Zhao,Jiafeng Wang,Hong Zhang,Lihua Hong,He Li,Hongze Che,Zhimin Zhang
Summary Pulpitis suppressed the level of let-7c-5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let-7c-5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let-7c-5p in DPSCs was up-regulated, and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let-7c-5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected. The administration of LPS suppressed the cell proliferation of DPSCs and suppressed calcium deposition, activity of alkaline phosphatase (ALP), and levels of OCN, OPN, OSX, MSX2, and RUNX2 in inflamed DPSCs. The impaired osteogenic differentiation of inflamed DPSCs was associated with the increased levels of HMGA2, p-PI3K, and p-Akt. In let-7c-5p-overexpressed inflamed DPSCs, the proliferation and osteogenic differentiation potential of DPSCs were restored, and the activation of HMGA2/PI3K/Akt signalling was inhibited. In rat pulpitis models, the injection of let-7c-5p agomir restored the osteogenic differentiation potential of dental pulp cells and inhibited HMGA2/PI3K/Akt signalling. The findings demonstrated the anti-inflammation and pro-osteogenesis effect of let-7c-5p during the attack of pulpitis, which depended on the inhibition of HMGA2/PI3K/Akt signalling.
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International Journal of Nanomedicine
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2018
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IF 4.37
Shuying Hu,Hanbang Chen,Xuefeng Zhou,Gang Chen,Ke Hu,Yi Cheng,Lili Wang,Feimin Zhang
Introduction Scaffold structure plays a vital role in cell behaviors. Compared with two-dimensional structure, 3D scaffolds can mimic natural extracellular matrix (ECM) and promote cell–cell and cell–matrix interactions. The combination of osteoconductive scaffolds and osteoinductive growth factors is considered to have synergistic effects on bone regeneration. Materials and methods In this study, core–shell poly(lactide-co-glycolide) (PLGA)/polycaprolactone (PCL)–BMP-2 (PP–B) fibrous scaffolds were prepared through coaxial electrospinning. Next, we fabricated 3D scaffolds based on PP–B fibers with thermally induced self-agglomeration (TISA) method and compared with conventional PLGA/PCL scaffolds in terms of scaffold morphology and BMP-2 release behaviors. Then, rat adipose-derived stem cells (rADSCs) were seeded on the scaffolds, and the effects on cell proliferation, cell morphology, and osteogenic differentiation of rADSCs were detected. Results The results demonstrated that 3D scaffold incorporated with BMP-2 significantly increased proliferation and osteogenic differentiation of rADSCs, followed by PP–B group. Conclusion Our findings indicate that scaffolds with 3D structure and osteoinductive growth factors have great potential in bone tissue engineering.
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Stem Cells Translational Medicine
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2019
·Vol. 8
·期 9
·971-982
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IF 5.962
Lu Wei,Xu Jian,Dong Shikui,Xie Guoming,Yang Shuanghui,Huangfu Xiaoqiao,Li Xiaoxi,Zhang Yang,Shen Peng,Yan Zhaowen,Liu Haifeng,Deng Zhenhan,Zhao Jinzhong
As a regular adoptable material for anterior cruciate ligament (ACL) reconstruction, free tendon allograft exhibits unsatisfactory outcomes, such as retarded ligamentization and tendon–bone integration. The application of bone marrow-derived mesenchymal stem cells (BMSCs), as well as a decellularized free tendon allograft developed by our group, was proven to be effective in improving ACL reconstruction results. This study aimed to investigate the efficacy and feasibility of decellularized allogenic semitendinous tendon (ST) combined with autologous BMSCs used as a substitute to free tendon allograft in a rabbit model. This study finally shows that the decellularized allogenic ST combined with autologous BMSCs could significantly improve ACL reconstruction results compared with allograft. Stem Cells Translational Medicine 2019;8:971–982Significance StatementFree tendon allograft exhibits unsatisfactory outcomes, such as retarded ligamentization and tendon–bone integration. The application of bone marrow-derived mesenchymal stem cells, as well as a decellularized free tendon allograft developed by the authors, was proven to be effective in improving anterior cruciate ligament reconstruction results.
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JOURNAL OF CONTROLLED RELEASE
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2015
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IF 7.705
Tian-Yuan Zhang,Bing Huang,Hai-Bin Wu,Jia-He Wu,Li-Ming Li,Yan-Xin Li,Yu-Lan Hu,Min Han,You-Qing Shen,Yasuhiko Tabata,Jian-Qing Gao
The success of conventional suicide gene therapy for cancer treatment is still limited because of lack of efficient delivery methods, as well as poor penetration into tumor tissues. Mesenchymal stem cells (MSCs) have recently emerged as potential vehicles in improving delivery issues. However, these stem cells are usually genetically modified using viral gene vectors for suicide gene overexpression to induce sufficient therapeutic efficacy. This approach may result in safety risks for clinical translation. Therefore, we designed a novel strategy that uses non-viral gene vector in modifying MSCs with suicide genes to reduce risks. In addition, these cells were co-administrated with prodrug-encapsulated liposomes for synergistic anti-tumor effects. Results demonstrate that this strategy is effective for gene and prodrug delivery, which co-target tumor tissues, to achieve a significant decrease in tumor colonization and a subsequent increase in survival in a murine melanoma lung metastasis model. Moreover, for the first time, we demonstrated the permeability of MSCs within tumor nests by using an in vitro 3D tumor spheroid model. Thus, the present study provides a new strategy to improve the delivery problem in conventional suicide gene therapy and enhance the therapeutic efficacy. Furthermore, this study also presents new findings to improve our understanding of MSCs in tumor-targeted gene delivery.
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MATERIALS LETTERS
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2016
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IF 2.437
Peng Zou,Hairong Liu,Yongsheng Li,Jiying Huang,Yao Dai
The proliferation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro is a key challenge for cartilage tissue engineering and their clinical applications. In this study, novel dextran grafting PHBV (PHBV-DEX) fibrous scaffolds were fabricated via surface modification. Compared with the electrospun PHBV fibrous scaffolds, dextran modified ones exhibited significantly enhanced surface hydrophilicity and bioactivity. The water contact angle (WCA) of those scaffolds was reduced from 117.3±4.30° to 56.03±1.13° after dextran modification. PHBV-DEX scaffold significantly promoted the growth of BMSCs compared with unmodified one, suggesting that it can be potentially applied in tissue engineering.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Yue Zhang,Hui Zhao,Qianxi Feng,Rui Guo,Li Zhong,Shengxian Liang
Benzotriazole ultraviolet stabilizers (BUVSs) are pervasive environmental contaminants that pose significant risks to human health. This study evaluated the effects of three typical BUVSs (UV-328, UV-329, and UV-P) on human mesenchymal stem cells (hMSCs), which play crucial roles in tissue maintenance and repair. hMSCs were exposed to BUVSs across a range of concentrations, and their maintenance and differentiation capacities were assessed. At concentrations below 50 μM, no significant cytotoxicity was observed. However, at non-cytotoxic doses, UV-P exhibited stronger effects on the differentiation of hMSCs compared to UV-328 and UV-329, significantly inhibiting adipogenesis and enhancing osteogenesis. Mechanistically, UV-P was found to significantly enrich the PPAR signaling pathway during both differentiation processes. Dual-luciferase reporter assays confirmed UV-P's interaction with PPARγ_LBD at an alternate binding site outside the canonical pocket. These findings raise concerns about the health impacts of BUVSs, particularly UV-P, and underscore the need for further investigation into their toxicological profiles.
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JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-20
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IF 10.6
An Na,Yan Xiaoyuan,Qiu Qiujing,Zhang Zeying,Zhang Xiyue,Zheng Bowen,Zhao Zhenjin,Guo Jiajie,Liu Yi
Background Bone defects in the maxillofacial region restrict the integrity of dental function, posing challenges in clinical treatment. Bone tissue engineering (BTE) with stem cell implants is an effective method. Nanobiomaterials can effectively enhance the resistance of implanted stem cells to the harsh microenvironment of bone defect areas by promoting cell differentiation. Graphene oxide quantum dots (GOQDs) are zero-dimensional nanoscale derivatives of graphene oxide with excellent biological activity. In the present study, we aimed to explore the effects of GOQDs prepared by two methods (Y-GOQDs and B-GOQDs) on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), as well as the effect of gelatin methacryloyl (GelMA)-encapsulated GOQD-induced hPDLSC sheets on the repair of mandibular periodontal defects in rats. We also explored the molecular biological mechanism through which GOQD promotes bone differentiation.Results There were significant differences in oxygen-containing functional groups, particle size and morphology between Y-GOQDs and B-GOQDs. Y-GOQDs promoted the osteogenic differentiation of hPDLSCs more effectively than did B-GOQDs. In addition, GelMA hydrogel-encapsulated Y-GOQD-induced hPDLSC cell sheet fragments not only exhibited good growth and osteogenic differentiation in vitro but also promoted the repair of mandibular periodontal bone defects in vivo. Furthermore, the greater effectiveness of Y-GOQDs than B-GOQDs in promoting osteogenic differentiation is due to the regulation of hPDLSC mitochondrial dynamics, namely, the promotion of fusion and inhibition of fission.Conclusion sOverall, Y-GOQDs are more effective than B-GOQDs at promoting the osteogenic differentiation of hPDLSCs by regulating mitochondrial dynamics, which ultimately contributes to bone regeneration via the aid of the GelMA hydrogels in vivo.Graphical Abstract
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Neural Regeneration Research
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2024
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IF 5.9
Li Shiming,Li Jianfeng,Chen Guoliang,Lin Tao,Zhang Penghui,Tong Kuileung,Chen Ningning,Liu Shaoyu
We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single–cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 ( Tsc2 ), solute carrier family 16 member 3 ( Slc16a3 ), and forkhead box protein P1 ( Foxpl ). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone. Furthermore, in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition, Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.
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Bioactive Materials
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2025
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IF 20.3
Jiabin Zhang,Xiaodie Chen,Yurong Chai,Yuanyuan Jin,Fenfang Li,Chenya Zhuo,Yanteng Xu,Haixia Wang,Enguo Ju,Yeh-Hsing Lao,Xi Xie,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low in-vivo integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.
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