Regenerative Biomaterials
·
2025
·
IF 8.1
Yan Xin,Li Xiangdong,Zhang Qi,He Xinlin,Chen Qi,Mai Sui
Human dental pulp stem cells (hDPSCs) exhibit replicative senescence during in vitro expansion, leading to a reduction in osteogenic differentiation capacity and thereby limiting their potential for bone defect regeneration. Magnesium ion (Mg2+), one of the most abundant divalent cations in the human body, is involved in numerous physiological processes. Mg2+ deficiency has been closely associated with bone fragility and various systemic aging-related diseases, underscoring its critical role in aging and bone metabolism. However, the effects of Mg2+ on mesenchymal stem cell (MSCs) replicative senescence remain poorly understood. In this study, we developed magnesium-doped bioactive glass (Mg-BG) powder with a graded magnesium doping ratio through the sol-gel method, and characterized the pore structure and ion release profiles of each Mg-BG group. We demonstrated that 20 Mg-BG (Mg-BG containing 20 mol% MgO) can effectively reverse the replicative senescence of hDPSCs, improve mitochondrial function, reduce ROS levels, and enhance the expression of surface markers associated with differentiation, migration, and adhesion in replicatively senescent hDPSCs, thereby enhancing their osteogenic differentiation potential. Furthermore, in vivo experiments using a rat calvarial defect model also confirmed that 20 Mg-BG significantly enhances bone defect repair mediated by replicatively senescent hDPSCs. Mechanistically, we found that the IKBKGP1-mediated NF-κB pathway may play a key role in this process, as revealed by transcriptome sequencing. These findings indicate that Mg-BG could serve as an effective, innovative approach to reverse replicative senescence in hDPSCs and enhance their bone defect repair capabilities.
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DOI
PubMed
高影响因子
American Journal of Translational Research
·
2025
·Vol. 17
·期 10
·7749
·
IF 1.6
Xiaowen Li,Ruikang Guo,Lingling Liang,Hao Liang,Guangqi Zhou,Qinglan Lu,Yonghui Huang,Zhen Qi,Xiaojie Li
Objective: Periodontitis, a prevalent oral disease leading to alveolar bone defects, remains a primary cause of tooth loss in adults. The biologic mechanisms driving bone loss in periodontitis are still poorly understood, limiting the development of genetic treatment. This study investigates potential therapeutic targets for alveolar bone loss by analyzing transcriptomic data related to the osteogenic differentiation of induced pluripotent stem cells (iPSCs). Methods: Using in vitro and in vivo models, we examined the role of neuropeptide Y receptor Y1 (NPY1R) and the PI3K-AKT-mTOR (PAM) signaling pathway in osteogenic differentiation and bone loss. A combination of bioinformatics, molecular biology, and histologic techniques was employed to pinpoint key signaling events that influence bone remodeling in periodontitis and to identify potential intervention points. Results: Transcriptomic profiling during iPSC osteogenic differentiation revealed significant upregulation of neuropeptide Y (NPY) and NPY1R. Suppression of NPY1R reduced the osteogenic capacity of iPSCs. Activation of the PAM pathway was observed during osteogenesis, and treatment with LY294002, a PAM pathway inhibitor, led to decreased osteogenic activity. In vivo experiments using a rat periodontitis model confirmed increased expression of NPY1R and activation of the PAM pathway, suggesting a role in bone repair processes. Conclusion: The NPY/NPY1R axis and the PAM signaling pathway appear to regulate bone regeneration and may be involved in preventing alveolar bone loss in periodontitis. These findings provide a new direction for therapy targeting bone defects associated with periodontal disease.
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高影响因子
American Journal of Translational Research
·
2019
·
IF 3.266
Zhao Wang,Hong-Wei Bao
Our aim was to study the osteogenic effect of cnidium lactone for bone marrow mesenchymal stem cells (BMSCs) and its potential mechanism. BMSCs were isolated and identified by flow cytometry and multidirectional differentiation capacity. Cell Counting Kit-8 (CCK-8) was used to identify the optimal concentration of cnidium lactone. Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) was performed to identify whether cnidium lactone has effect on osteogenesis at early and late phase respectively. Moreover, we used estrogen receptor antagonist, ICI182780, to identify the receptor of cnidium lactone. The expression of Runt-related transcription factor 2 (RUNX2), Osterix (OSX), osteopontin (OPN), estrogen receptor (ER), Smad4, p-Smad1, Smad1 and bone morphogenetic protein 2 (BMP-2) protein were measured by PCR and western blot. Cnidium lactone (2 μM) demonstrated increased osteogenesis after osteogenic inducible medium (OIM) induction, as evidenced by more ALP activity and mineralization. When blocked with ICI182780, osteogenesis capacity was decreased. Moreover, the polymerase chain reaction (PCR) and western blotting results indicated that cnidium lactone enhanced ER, BMP2, Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Cnidium lactone can effectively stimulates osteogenic differentiation of BMSCs via BMP-2/Smad-Signaling cascades mediated by ER.
研究领域:
药理学
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干细胞生物学
·
骨骼再生
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PubMed
高影响因子
CELL AND TISSUE RESEARCH
·
2023
·
IF 3.6
Yuan Haojie,Yu Junbo,Liu Chun,Zhao Heyan,Xue Jianhua,Liu Jiajia,Yang Yang
This study aims to discuss the role of exosomes KCNQ10T1 derived from bone marrow mesenchymal stem cells (BMMSCs) in sepsis and to further investigate its potential molecular mechanisms. Exosomes extracted from BMMSCs are identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Fluorescence labeling is applied to detect the internalization of exosomes in receptors. The proliferation ability, migration ability, and invasion ability of HUVECs are determined by CCK-8, EdU, wound healing, and Transwell. The levels of inflammatory cytokines in sepsis cells are quantitatively detected by ELISA. Kaplan–Meier survival curve is used to describe the overall survival. RT-qPCR is used to detect mRNA expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-154-3p and the interaction is verified by luciferase reporter assay. Exosomes derived from BMMSCs alleviated the toxicity in sepsis cell models and animal models. In mice with septic cell models, exosomal KCNQ10T1 was down-regulated and associated with lower survival. Overexpression of KCNQ10T1 inhibited the proliferation and metastasis of LPS-induced HUVECs. Further research illustrated that miR-154-3p was the downstream target gene of KCNQ1OT1 and RNF19A was the downstream target gene of miR-154-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated sepsis progression by targeting miR-154-3p/RNF19A axis. Our study demonstrates that the exosomal KCNQ1OT1 suppresses sepsis via mediating miR-154-3p/RNF19A, which provides a latent target for sepsis treatment.
研究领域:
分子生物学
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干细胞研究
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免疫学
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细胞生物学
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医学遗传学
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PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Yantao Zheng,Gang Wu,Limei Chen,Ying Zhang,Yuwei Luo,Yong Zheng,Fengjun Hu,Tymor Forouzanfar,Haiyan Lin,Bin Liu
Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with [email protected] α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.
研究领域:
神经科学
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干细胞疗法
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生物材料
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再生医学
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PubMed
高影响因子
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-15
·
IF 5.116
Shen Ying-Shan,Chen Xiao-Jun,Wuri Sha-Na,Yang Fan,Pang Feng-Xiang,Xu Liang-Liang,He Wei,Wei Qiu-Shi
Objectives Polydatin (PD), extracted from Polygonum cuspidatum , has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/β-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. Materials and methods hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. Results In vitro, 30 μM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2 , Osteopontin , DLX5 , β-catenin , TAZ , and Osteocalcin ( OCN ). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/β-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. Conclusion Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/β-catenin pathway.
研究领域:
药理学
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干细胞生物学
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骨骼生物学
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分子生物学
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PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Jiankun Guan,Yuxin Wu,Xin Liu,Huimin Wang,Ningbing Ye,Zheng Li,Chen Xiao,Zhijie Zhang,Zifu Li,Xiangliang Yang
Cancer stem cells (CSCs) present grand challenges for triple-negative breast cancer (TNBC). Conventional chemotherapy drugs, including Camptothecin (CPT), not only cannot eradicate CSCs but also foster a suppressive immune microenvironment for the initiation and proliferation of CSCs. Herein, we report a novel prodrug CPT–SS–NLG919 (CN) and its nanoformulation [email protected] ( [email protected] ), which potently suppress CSCs by regulating CSCs niche in murine TNBC 4T1 tumors. Via inducing immunogenic cell death (ICD) and simultaneous inhibiting indoleamine 2, 3-dioxygenase (IDO), CN and [email protected] promote DC maturation, decrease Treg cells, mitigate tryptophan consumption, and reduce the amount of IL-6, IL-13, and TGF-β, converting CSCs niche to a hostile condition for CSCs to live in and eliminating CSCs efficiently, thereby inducing efficient tumor inhibition in 4T1 tumor models. Our work represents a new paradigm of eliminating CSCs by regulating tumor immune microenvironment and suggests that CN and its nanoformulation [email protected] are promising candidates for the treatment of intractable TNBC.
研究领域:
肿瘤学
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药理学
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免疫学
·
纳米技术
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PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 41
·19579-19585
·
IF 7.233
Zheng Guo,Xiaohua Zhu,Shigong Wang,Chunyang Lei,Yan Huang,Zhou Nie,Shouzhuo Yao
As an emerging two-dimensional material, MXenes have attracted much attention due to their unique physicochemical properties, but their application in biosensing has been lagging far behind because of their poor salt tolerance. Herein, a titanium carbide MXene quantum dot (Ti3C2 QD)-based fluorescent probe for the alkaline phosphatase (ALP) activity assay and embryonic stem cell (ESC) identification was developed by taking advantage of the inner filter effect (IFE). Ti3C2 QDs with ∼4.2 nm in diameter were prepared from Ti3C2 MXenes by hydrothermal treatment, exhibiting excellent salt tolerance, anti-photobleaching and dispersion stability in aqueous solution. Owing to the remarkable overlap between the absorption spectrum of p-nitrophenol (p-NP) and the excitation and emission spectrum of Ti3C2 QDs, p-NP generated from ALP-catalyzed dephosphorylation of the substrate, p-nitrophenyl phosphate (p-NPP), can effectively quench the fluorescence of Ti3C2 QDs through the IFE. As a result, sensitive fluorometric analysis of ALP activity was achieved without complicating the conventional colorimetric ALP detection system. The proposed assay was successfully applied to determine ALP activity with a low limit of detection (0.02 U L−1) as well as monitoring the enzyme activity in real time. Finally, accurate analysis of ALP, the biomarker of ESC, in ESC lysates was also achieved using this IFE-based method, affording an alternative method for ESC identification.
研究领域:
生物传感
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分析化学
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细胞生物学
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2014
·Vol. 8
·期 3
·935-942
·
IF 0.941
Wei Zhang,Jiabo Hu,Quanhui Ma,Sanqiang Hu,Yanyan Wang,Xiangmei Wen,Yongbin Ma,Hong Xu,Hui Qian,Wenrong Xu
An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70˚C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 µg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 µg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at -70˚C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70˚C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70˚C short-term or liquid nitrogen cryopreservation.
研究领域:
干细胞生物学
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细胞培养
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低温生物学
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PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 3.7
Bai Qiufang,Li Zhe,Chen Jing,Liu Man,Shao Xiaodan,Chen Xiaochi,Piao Fengyuan,Fang Linlin
N-hexane is a widely used aliphatic hydrocarbon solvent that can cause central–peripheral neuropathy. Compared to peripheral nerve tissue, spinal nerve tissue is more vulnerable and typically non-regenerable. However, no effective treatments are currently available. Stem cells are attractive therapeutic cells because of their extensive self-renewal and pluripotent differentiation abilities. Accordingly, numerous studies are focused on their restorative potential. In the present study, we investigated the effects and mechanisms of stem cell therapy on spinal nerves damaged by 2,5-HD (a proximate toxic metabolite of n-hexane). Our results showed that spinal axonopathy induced by 2,5-HD was alleviated by bone mesenchymal stem cell (BMSC) transplantation. Further, by examining the expression of molecules associated with axonal outgrowth, NGF signaling was found to be involved in the regeneration of spinal axons. Moreover, intervention experiments showed that PTEN was also an essential component of BMSC therapy. Conclusively, our data suggested that BMSC transplantation can alleviate spinal injury induced by 2,5-HD through AKT/mTOR/CREB by NGF-dependent and -independent pathways.
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Xiangyu Sun,Jing Yan,Fengti Guo,Hao Sun,Xiaoqi Xie,Nan Su,Jingxuan Sun,Yumei Niu,Lin Zhang,Lina He
Stem cell transplantation holds great promise for facial nerve repair, yet its efficacy is largely constrained by the excessive accumulation of reactive oxygen species (ROS) and the highly inflammatory microenvironment. Thus, developing bioactive scaffolds with robust antioxidant capacity for stem cell transplantation remains a challenge. In this study, an injectable and self-healing composite hydrogel composed of chitosan, graphene oxide, and cerium oxide nanoparticles (CeNPs) was developed to provide structural support for the neural conduit, create a favorable microenvironment for human dental pulp stem cells (hDPSCs), and effectively promote facial nerve regeneration. The hydrogel exhibited intrinsic shear-thinning, self-recovery, and self-healing properties, ensuring its adaptability to irregular nerve defects and suitability for minimally invasive delivery, while its ROS-scavenging activity effectively reshaped the injury microenvironment to mitigate oxidative stress and inflammatory responses in the transplanted cells. In vitro, the composite hydrogel promoted the specific migration of hDPSCs, while alleviating cellular oxidative damage by modulating the PI3K/AKT signaling pathway to facilitate M2 polarization of macrophages. In a facial nerve defect model, treatment with the hydrogel in combination with hDPSCs significantly improved neurological function and tissue regeneration, achieving morphological and functional outcomes comparable to those of autologous nerve grafts. Collectively, this CeNPs-integrated hydrogel provides adaptive structural support, modulates the injury microenvironment, and promotes stem cell migration, representing a promising bioactive platform with clinical translational potential for facial nerve repair.
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PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2026
·
IF 5.8
Sicheng Deng,Xiaona Wu,Shaoyong Chen,Yulu Xie,Lingsan Ran,Haiyan Xue,Qiuling Pang,Kuangdi Xin,Yuehua You,Rongmin Qiu
Objective This study aims to provide experimental basis that underpins the potential application of graphene quantum dots (GQDs) as a therapeutic strategy for periodontitis. Methods and Materials An inflammatory circumstance was established by Porphyromonas gingivalis lipopolysaccharide (P.g-LPS). The effects of GQDs on human periodontal ligament stem cells (hPDLSCs) proliferation, migration and osteogenic differentiation in vitro were assessed using Cell Counting Kit-8 (CCK-8), Transwell assay, alkaline phosphatase (ALP) and alizarin red S (ARS) staining, ALP activity and ARS semi-quantification. The anti-inflammatory activity was evaluated by Enzyme-linked immunosorbent assay (Elisa). The underlying osteogenic mechanism was initially explored by mRNA sequencing (mRNA-Seq) and further correlated with gene and protein expression changes via quantitative real-time PCR (RT-qPCR) and Western blot (WB) analysis. Furthermore, the in vivo efficacy and biosafety of GQDs were evaluated in a rat periodontitis model using micro computed tomography (Micro-CT) and histomorphometric analysis. Result In vitro , GQDs exhibited favorable cytocompatibility and enhanced the viability, migration, osteogenesis of hPDLSCs under normal conditions. In inflammatory microenvironment, GQDs significantly counteracted the suppression of P.g-LPS on hPDLSCs proliferation, migration, osteogenic differentiation, and notably reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Mechanistically, mRNA-Seq identified the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways as potentially associated in the osteogenic modulation of GQDs on hPDLSCs in both normal and inflammatory settings. Subsequent validation showed that GQDs upregulated the mRNA and total protein levels of p38, PI3K, and Akt. In vivo , local administration of GQDs attenuated alveolar bone resorption, suppressed osteoclast activity and formation, and reduced inflammatory infiltration with no observable systemic toxicity. Conclusion GQDs possess the capacity to counteract inflammation-induced damage and promote osteogenic restoration both in vitro and in vivo , highlighting their potential dual functionality in periodontal regeneration.
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高影响因子
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