CHEMICO-BIOLOGICAL INTERACTIONS
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2020
·
IF 3.723
Meihui Chen,Dan Luo,Jiheng Zhan,Yu Hou,Shudong Chen,Xing Li,Dingkun Lin
Bone mesenchymal stem cells (BMSCs) are a well-known donor graft source due to their potential for self-renewal and differentiation into multi-lineage cell types, including osteoblasts that are critical for fracture healing. Fasudil (FAS), a Rho kinase inhibitor, has been proven to induce the differentiation of bone marrow stem cells (BMSCs) into neuron-like cells. However, its role in the osteogenesis of BMSCs remain uncertain. Herein, we for the first time studied the effects of FAS on osteogenic differentiation in a mouse fracture model and further explored the involved mechanisms in mouse BMSCs. The results showed that FAS stimulated bone formation in the fracture mouse model. Additionally, at 30 μM, FAS significantly promotes alkaline phosphatase activity, mineralization, and the expression of osteogenic markers COL-1, RUNX2 and OCN in murine BMSCs. Blocking of P38 by SB202190 significantly reversed the effects of FAS, in vitro, suggesting that P38, but not ERK or JNK activation is required for FAS-induced osteogenesis. Collectively, our results indicate that FAS may be a promising agent for promoting fracture healing.
研究领域:
干细胞生物学
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药理学
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骨科学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 47
·9300-9311
·
IF 4.543
Zhao-Hui Huang,Peng-Fei Wei,Le Jin,Xiao-Qing Hu,Qing Cai,Xiao-Ping Yang
Nanomedicines have found promising applications in regulating the biological behaviors of cells because of the cell endocytosis effect. To enhance the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs), which is one of the key issues in relation to bone regeneration, a biodegradable simvastatin-bearing polyphosphazene prodrug was synthesized and made into nanoparticles (NPs). At the same time, photoluminescent tryptophan ethyl ester and hydrolyzable glycine ethyl ester were introduced as co-substituted side groups onto the polyphosphazene backbone. The resultant polymer, poly(simvastatin-co-ethyl tryptophanato-co-ethyl glycinato)phosphazene (PTGP-SIM), displayed the expected features of photoluminescence, degradability and sustained SIM release. Endocytosis of PTGP-SIM NPs by BMSCs and the location of internalized NPs, were visualized via the inherent photoluminescence features of PTGP-SIM. Thus, simvastatin was released inside the cells directly along with polymer degradation and could play a role in promoting osteogenic differentiation efficiently at quite a low local concentration. From the results, the present study suggested a very promising biomaterial for use as a flexible and functional carrier for bioactive components, which could find wide applications in relation to tissue regeneration.
研究领域:
纳米技术
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生物材料
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组织工程
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药学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2022
·
IF 3.682
Lei Fu,Wenwen Zhao,Liwen Zhang,Chenyuan Gao,Xin Zhang,Xiaoping Yang,Qing Cai
The heterogeneous nature of osteochondral tissue requires the construction of implant with biomimetic gradients. Electrospun fibrous meshes with different designs provide the feasibility in arranging such a kind of gradient structure via layer-by-layer stacking. In this study, a kind of triphasic implant was constructed by layering pre-differentiated cell sheets, which were hold by electrospun poly(L-lactide)/gelatin (PLLA/Gel) fibrous meshes containing hyaluronic acid and chondroitin sulfate for the cartilage layer or hydroxyapatite for the bone layer. As for the calcified interlayer, the bone marrow mesenchymal stromal cells (BMSCs) seeded on PLLA/Gel fibrous mesh was pre-differentiated with a mixed osteoinductive/chondroinductive (1:1) medium. With this gradient construct being implanted in rabbit knee osteochondral defect, it was found that both the cartilage and subchondral bone were regenerated effectively with reproduced tidal line structure. The importance of implants with biomimetic gradients for osteochondral defect repair was confirmed, and cell sheets on electrospun fibrous meshes were flexible for gradient structure construction via the layer-by-layer stacking technology. HighlightsComposite fibrous meshes with tissue-specific components are electrospun.Confluent BMSCs on fibrous meshes are chondrogenically or osteogenically induced.BMSCs hypertrophy is induced with the mixture of chondroinductive and osteoinductive medium.The pre-differentiated cell/mesh complexes are stacked layer-by-layer to form gradient construct.The gradient construct efficiently promotes osteochondral regeneration in rabbit joint.
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DOI
PubMed
高影响因子
Theranostics
·
2026
·Vol. 16
·期 9
·4521
·
IF 14.9
Zhe Liu,Qinzhou Zheng,Dong Zhou,Anqi Lin,Lan Xiao,Haifeng Liu,Keqin Ji,Huifen Qiang,Xinxin Sui,Yulin Li,Yan Wu,Jie Gao,Lan Liao,Xiaohuan Yuan
Background The process of healing wounds in diabetic patients is intricate and is notably obstructed by a disordered wound microenvironment, characterized by chronic inflammation and elevated blood glucose. The combination of stem cell therapy and drug treatment is seen as a promising application in future. However, the limited proliferative capacity of stem cells and inadequate drug availability present significant challenges for achieving optimal therapeutic outcomes. Methods In this study, open porous poly (lactic‒coglycolic acid) (PLGA) microspheres were designed and synthesized via gas-assisted volatilization microemulsion technology. These microspheres encapsulate curcumin and allow its slow release, thereby enhancing wound repair. The large pores in the microspheres provide ample support for bone marrow stem cells (BMSCs), enabling continuous drug release over a period of 35 days. Results The sustained release of curcumin promoted stem cell proliferation and maintained stem cell activity. Additionally, it facilitates remodeling of the wound immune microenvironment. Additionally, the microspheres can activate mitochondrial autophagy in cells, effectively alleviating wound inflammation. Conclusions The combined actions of curcumin and stem cells aid in regenerating blood vessels and revitalizing the collagen network where the injury occurred, thus improving wound healing capabilities. Consequently, integrating drugs with stem cells and microspheres holds significant potential for diabetic wound treatment.
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DOI
PubMed
高影响因子
Genes & Diseases
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2026
·
IF 14.6
Xinhang Li,Yi Xie,Wenyan Ren,Qing Liu,Qiming Pang,Wenting Liu,Xin Li,Bin He,Dongmei He,Xinyue Wan,Jia Liu,Jie Cai,Baicheng He,Wei Huang,Fang He
Renal osteodystrophy is a debilitating complication of chronic kidney disease characterized by deteriorated bone microarchitecture and impaired bone formation, leading to increased fracture risk. Despite the pressing need for anabolic therapies, the cellular mechanisms by which uremic stress compromises osteoprogenitor function remain poorly defined. Here, metabolomic profiling of renal osteodystrophy patient cohorts revealed a profound depletion of circulating betaine. We show that betaine supplementation not only rescued the osteogenic differentiation of bone marrow-derived mesenchymal stem cells challenged with the uremic toxin indoxyl sulfate but also ameliorated skeletal deterioration in a rat model of chronic kidney disease. Mechanistically, we demonstrated that indoxyl sulfate triggered ferroptosis in bone marrow-derived mesenchymal stem cells—characterized by iron-dependent lipid peroxidation and aberrant HMOX1 up-regulation—thereby arresting osteogenesis. Betaine mitigates this ferroptotic stress through a novel post-transcriptional mechanism. Specifically, betaine down-regulated the RNA-binding protein hnRNP A1, preventing the recruitment of the CNOT1 deadenylase complex. This inhibition stabilized Abcg1 mRNA, leading to restored ABCG1 expression. Functional perturbation studies confirmed that the ABCG1–HMOX1 axis was indispensable for the anti-ferroptotic and osteoprotective effects of betaine. Collectively, our findings delineate a Betaine–hnRNP A1/CNOT1–ABCG1–HMOX1 signaling cascade that links metabolic deficiency to ferroptosis-driven osteogenic failure, positioning betaine as a promising anabolic therapeutic strategy for renal osteodystrophy.
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DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Liang-xu Wei,Yan Cui,Yan-lan Lv,Qian-yun Ye,Jian-bing Chen,Xiao-yao Zhan,Zi-jun Zhu,Xiao-feng Zhu,Bei Zhou
Cadmium (Cd), a heavy metal pollutant that accumulates in organisms, is osteotoxic and contributing to the development of osteoporosis. Lycium barbarum polysaccharide (LBP), a polysaccharide obtained from the Chinese medicinal plant Lycium barbarum, exhibits protective effects against oxidative stress and cellular damage. However, it is unclear whether LBP can effectively inhibit Cd-induced osteotoxicity. This study investigated whether LBP alleviates Cd-induced osteogenic suppression in bone marrow mesenchymal stem cells (BMSCs) via autophagy modulation. Cell viability, osteogenic markers (ALP, BMP2, COL1, RUNX2), and mineralization were assessed using CCK-8, qPCR, Western blot, and alizarin red staining. Autophagy flux was evaluated via GFP-mCherry-LC3B transfection and protein markers (LC3-II, P62, BECN). We confirmed that Cd inhibited the formation of cellular autophagosomes while adversely affecting BMSCs. However, LBP mitigated the Cd-induced osteogenic inhibitory effect by stimulating the autophagy processes and facilitating the formation of autophagosomes and autolysosomes. In conclusion, LBP is a potential bone-enhancing agent that can improve cell viability and osteogenic differentiation while mitigating the detrimental effects of Cd on BMSCs through the activation of autophagy.
研究领域:
毒理学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
·
IF 16.744
Chengwei Wu,Xuzhao He,Wenjian Weng,Tianfang Zhang,Donghua Huang,Kui Cheng,Zuobing Chen
Bone marrow mesenchymal stem cells (BMSCs) could be regulated through their microenvironment, which includes biological cues of extracellular matrix (ECM) and other endogenous physical cues. In this work, cell-derived ECM was used as a framework to prepare extracellular matrix/polypyrrole composite films by chemical polymerization of polypyrrole (Ppy). The composite film retained the microstructure of ECM, while the microscopic surface exhibited dual-exposure of ECM and Ppy. The content of Ppy had a decisive influence on the protein exposure area and electrochemical performance to generate different biological or electrical microenvironment. It was worth noting that the ECM/Ppy composite films with appropriate Ppy content had unique biological microenvironments that could promote the osteogenic differentiation of BMSCs. In addition, the electrochemical performance of ECM/Ppy composite films had been significantly improved compared with ECM, which meant that they were electroactive. When BMSCs were simultaneously affected by biological microenvironment and electrical microenvironment, this new composite electroactive film showed the best ability to promote osteogenic differentiation. Correspondingly, the microenvironment provided by ECM/Ppy composite films significantly up-regulated the expression of genes related to osteogenic differentiation of ALP, Col-I, and RunX-2. Furthermore, the electrical microenvironment had been shown to regulate the osteogenic differentiation of BMSCs through the influence on the intracellular calcium ion (Ca 2+ ) concentration and related signal pathways. This new composite electroactive biomaterial has unique biochemical properties and good electrochemical properties to construct biological and electrical microenvironment, having great potential in research and application of bone tissue regeneration and regenerative medicine.
研究领域:
生物材料学
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再生医学
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组织工程学
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DOI
高影响因子
MATERIALS & DESIGN
·
2025
·
IF 7.9
Jun Hu,Xiqiang Zhong,Jiacheng Wang,Minghai Dai,Liangle Liu,Xiaofu Pan
The clinical repair of spinal cord injury (SCI) has long been constrained by the twin challenges of a persistent hypoxic microenvironment at the injury site and the low survival rate of transplanted cells. This study innovatively constructs a three-dimensional (3D) oxygen-releasing scaffold Poly(lactic-co-glycolic acid (PLGA)-Calcium Peroxide (CPO)/Gelatin Methacryloyl (PLGA-CPO/GelMA) featuring a core–shell structure achieved via emulsification-photocrosslinking technology. PLGA-CPO microspheres provide sustained oxygen release for over 14 days, while the GelMA hydrogel establishes a biomimetic microenvironment. In vitro experiments confirmed that under hypoxic conditions, the hydrogel composite scaffold maintained the proliferative activity of the bone marrow mesenchymal stem cells during 3D co-culture. Furthermore, when co-cultured with neurons in a 2D system simulating the in vivo SCI environment, the scaffold significantly promoted neuronal survival and proliferation. In a T9 complete transection SCI rat model, the scaffold transplantation group exhibited significantly improved Basso, Beattie, Bresnahan locomotor scores compared to control groups. Histological analysis revealed increased axonal regeneration, reduced glial scarring, and high survival rates of transplanted mesenchymal stem cells at the implantation site in the scaffold-treated group. Mechanistic studies demonstrated that the composite scaffold exerted a triple synergistic effect, encompassing promotion of angiogenesis and neural regeneration, alongside suppression of apoptotic responses. The developed Organic/Inorganic Composite scaffold sustainably ameliorates the injury microenvironment and synergistically enhances stem cell-mediated repair efficacy, providing a promising tissue engineering solution with significant potential for clinical translation in spinal cord injury.
研究领域:
生物医学工程
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组织工程
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神经再生
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干细胞治疗
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生物材料学
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转化医学
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创伤修复
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DOI
高影响因子
Materials Advances
·
2025
·
IF 4.7
Shengjie Wang,Wei Liu,Chao Yang,Xianlong Zhang,Chunming Lyu
This study aimed to develop a novel artificial joint prosthesis material with osteogenic properties. Deferoxamine mesylate (DFO) was immobilized on the porous surface of sulfonated polyetheretherketone (SPEEK) through polydopamine (PDA), resulting in a novel material designated as DFO-PDA@SPEEK (Abbrev. DFO-PS). DFO-PS induced macrophage M2 phenotype polarization, reduced inflammatory factor expression, promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and enhanced implant osseointegration and osteogenic capacity. In vitro evaluation demonstrated that DFO-PS significantly modulated immune and inflammatory responses, promoted angiogenesis, and enhanced osteogenic differentiation. In the rat model with femoral bone defect, in comparison to the control group, the DFO-PS group exhibited a 1.22-fold increase in trabecular thickness and a 1.51-fold enhancement in maximum pull-out force. This work demonstrates that DFO-PS represents a promising strategy for constructing multifunctional implants with biomineralization and immunomodulation properties for bone joint replacement.
研究领域:
生物材料学
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免疫学
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骨科医学
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DOI
高影响因子
Nanoscale
·
2023
·Vol. 15
·期 11
·5379-5390
·
IF 6.7
Chengwei Wu,Yuan Sun,Xuzhao He,Wenjian Weng,Kui Cheng,Zuobing Chen
Mild thermal stimulation in vivo could induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, nano-functionalized photothermal extracellular matrix (ECM) nanocomposite films were obtained through adding graphene during cell culture, so that graphene could directly integrate with the ECM secreted by cells. Owing to the similarity of the ECM to the in vivo microenvironment and the apparent photothermal effect of graphene nanoflakes, heat could be generated and transferred at the material–cell interface in a biomimetic way. It was demonstrated that such nanocomposite films achieved an interface temperature rise with light illumination. This could be easily sensed by BMSCs through the ECM. According to alkaline phosphatase, osteogenic related gene expression, mineral deposition, and upregulated expression of heat shock protein (HSP70) and p-ERK, composite films with proper illumination significantly promoted the differentiation of BMSCs into osteoblasts. This work endeavors to study the thermal regulation of BMSC differentiation and provide a new perspective on biocompatible osteo-implant materials which can be remotely controlled.
研究领域:
生物材料
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组织工程
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干细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8.2
Lili Hao,Wenjie Zhang,Xiaoting Peng,Yujia Bai,Cheng Tian,Yiwen Zhang,Di Li,Zhihui Feng,Baoshan Xu,Qiong Xu
Disordered osteogenic potential in bone marrow mesenchymal stem cells (BMSCs) is a hallmark of inflammatory jaw diseases. Recent studies suggest that inflammatory stimulating disrupts energy metabolism during BMSC osteogenesis. However, the impact of key metabolites on BMSC ossification remains unclear. In this study, a comprehensive targeted metabolomic analysis was performed during BMSC osteogenic differentiation, with and without inflammatory stimulation induced by lipopolysaccharide (LPS). We identified a significant downregulation of spermidine (SPD), along with methylated purines and pyrimidines, in the inflammatory environment. Exogenous SPD supplementation enhanced BMSC osteogenesis and increased N6-methyladenosine (m 6 A) methylation. Mechanistically, SPD elevated S-adenosylmethionine (SAM) levels and upregulated the methyltransferases METTL3 and METTL14. Similarly, betaine, a promoter of SAM synthesis, increased m 6 A methylation and improved BMSC osteogenic potential. In contrast, the METTL3/METTL14 inhibitor S-adenosylhomocysteine (SAH) reduced m 6 A methylation and negated SPD's osteogenic effects. This suggests that SPD enhances BMSC osteogenesis through m 6 A methylation regulation. Furthermore, SPD activated autophagy in BMSCs, while SAH inhibited SPD-induced autophagy. Notably, treatment with rapamycin (Rap), an autophagy inducer, restored both autophagy and osteogenic differentiation impaired by SAH. In vivo , SPD supplementation enhanced m 6 A methylation and facilitated bone regeneration in a rat model of inflammatory mandibular defects. In conclusion, this study demonstrates that SPD promotes the osteogenic potential of BMSCs through an m 6 A methylation–autophagy axis under inflammatory conditions, providing a novel therapeutic approach for inflammatory jaw diseases.
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DOI
PubMed
高影响因子
PeerJ
·
2023
·
IF 2.7
Yuanchun Liu,Wanyi Huang,Huiyang Wang,Wei Lu,Jiayu Guo,Li Yu,Lina Wang
Bone marrow-derived mesenchymal stem cells (BMSCs) are increasingly being used in bone marrow transplantation (BMT) to enable homing of the allogeneic hematopoietic stem cells and suppress acute graft versus host disease (aGVHD). The aim of this study was to optimize the labelling of BMSCs with superparamagnetic iron oxide particles (SPIOs), and evaluate the impact of the SPIOs on the biological characteristics, gene expression profile and chemotaxis function of the BMSCs. The viability and proliferation rates of the SPIO-labeled BMSCs were analyzed by trypan blue staining and CCK-8 assay respectively, and the chemotaxis function was evaluated by the transwell assay. The expression levels of chemokine receptors were measured by RT-PCR and flow cytometry. The SPIOs had no effect on the viability of the BMSCs regardless of the labelling concentration and culture duration. The labelling rate of the cells was higher when cultured for 48 h with the SPIOs. Furthermore, cells labeled with 25 µg/ml SPIOs for 48 h had the highest proliferation rates, along with increased expression of chemokine receptor genes and proteins. However, there was no significant difference between the chemotaxis function of the labeled and unlabeled BMSCs. To summarize, labelling BMSCs with 25 µg/ml SPIOs for 48h did not affect their biological characteristics and chemotaxis function, which can be of significance for in vivo applications.
研究领域:
干细胞研究
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）