PLATELETS
·
2026
·
IF 3.1
Shaochuan Wang,Debin Guo,Shidan Li,Ruohui Tang,Hao Jiang,Xiaoming Li,Youbin Li,Jing Yang,Lei Li,Jun Fei
Bone maintains a dynamic and stable state through the orchestration of osteoclasts and osteoblasts. Osteoblasts are derived mainly from mesenchymal stem cell (MSC) and are responsible for bone formation. The inhibition of osteoblast proliferation and differentiation is involved in many diseases, including osteoporosis, osteoarthritis, infected bone defects, and inflammatory aseptic loosening of implants. Given the currently limited treatment options, exploring new methods to promote bone formation is an important focus significant for orthopedists. Platelet-rich plasma (PRP), an autologous substance that is rich in various growth factors, is widely used in regenerative medicine. However, the effect of PRP on inflammatory bone destruction remains unclear. We investigated the effects of PRP on the viability of MSC, and the impact of different concentrations of PRP (1% and 3%, respectively) on cell death, proliferation, and differentiation. Furthermore, we tested the therapeutic effect of different concentrations of PRP (1% and 3%) on LPS-induced inflammatory bone destruction in vivo. PRP enhanced the cellular activity of MSC and promoted osteogenesis. A higher concentration of PRP (3%) primarily reduced the death and increased the proliferation of in LPS-treated MSC via the PI3K/AKT pathway, while a lower concentration of PRP (1%) promoted MSC differentiation into osteoblasts through the MAPK pathway. Consistent with in vitro experiments, we validated the protective effect of PRP against LPS-induced bone loss by increasing bone formation in vivo. These results suggest that different concentrations of PRP can ameliorate LPS-induced inflammatory bone loss through distinct mechanisms.
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Qingge Ma,Chenghao Song,Zhengmin Zhang,Feifei Li,Peng Yu,Ling Ye
The osteogenic differentiation of mesenchymal stem cells (MSCs) requires dynamic remodeling of the extracellular matrix (ECM) microenvironment. Biomimetic mineralization (BM) can recapitulate key features of the native bone microenvironment and thereby promote MSC osteogenesis. However, the development of artificial scaffolds capable of providing dynamically evolving mineralized niches for MSCs remains challenging, and the underlying osteogenic mechanisms are still poorly understood. In this study, a hierarchical graphene-doped polymethyl methacrylate (PMMA) scaffold was fabricated via vapor-induced phase separation. An organic-inorganic framework with continuous self-mineralization capability—composed of ovalbumin (OVA), tannins (TA), Ca 2+ , and PO 4 3- —was engineered on the graphene surface through a simple two-step immersion process. This bone tissue mimetic architecture, combined with sustained in situ mineralization, establishes an optimal dynamic niche that supports MSC adhesion and drives robust osteogenic differentiation. Furthermore, the self-mineralized calcium nodules synergize with MSC-mediated calcium deposition during osteogenesis, leading to accelerated scaffold remodeling and a significantly shortened bone repair timeline. Collectively, the hierarchical scaffold featuring a self-mineralizing MSC niche exhibits strong potential for the regeneration of critical-sized bone defects.
研究领域:
组织工程
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再生医学
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生物医学材料
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干细胞生物学
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骨生物学
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DOI
PubMed
高影响因子
Frontiers in Genetics
·
2021
·
IF 4.599
Zhang Jing,Gao Juan,Lin Dengna,Xiong Jing,Wang Jialei,Chen Junfeng,Lin Bingliang,Gao Zhiliang
Acute-on-chronic liver failure (ACLF) is a severe syndrome associated with high mortality. Alterations in the liver microenvironment are one of the vital causes of immune damage and liver dysfunction. Human bone marrow mesenchymal stem cells (hBMSCs) have been reported to alleviate liver injury via exosome-mediated signaling; of note, miRNAs are one of the most important cargoes in exosomes. Importantly, the miRNAs within exosomes in the hepatic microenvironment may mediate the mesenchymal stem cell (MSC)-derived regulation of liver function. This study investigated the hepatocyte exosomal miRNAs which are regulated by MSCs and the target genes which have potential in the treatment of liver failure. Briefly, ACLF was induced in mice using carbon tetrachloride and primary hepatocytes were isolated and co-cultured (or not) with MSCs under serum-free conditions. Exosomes were then collected, and the expression of exosomal miRNAs was assessed using next-generation sequencing; a comparison was performed between liver cells from healthy versus ACLF animals. Additionally, to identify the intracellular targets of exosomal miRNAs in humans, we focused on previously published data, i.e., microarray data and mass spectrometry data in liver samples from ACLF patients. The biological functions and signaling pathways associated with differentially expressed genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomics enrichment analyses; hub genes were also screened based on pathway analysis and the prediction of protein-protein interaction networks. Finally, we constructed the hub gene-miRNA network and performed correlation analysis and qPCR validation. Importantly, our data revealed that MSCs could regulate the miRNA content within exosomes in the hepatic microenvironment. MiR-20a-5p was down-regulated in ACLF hepatocytes and their exosomes, while the levels of chemokine C-X-C Motif Chemokine Ligand 8 (CXCL8; interleukin 8) were increased in hepatocytes. Importantly, co-culture with hBMSCs resulted in up-regulated expression of miR-20a-5p in exosomes and hepatocytes, and down-regulated expression of CXCL8 in hepatocytes. Altogether, our data suggest that the exosomal miR-20a-5p/intracellular CXCL8 axis may play an important role in the reduction of liver inflammation in ACLF in the context of MSC-based therapies and highlights CXCL8 as a potential target for alleviating liver injury.
研究领域:
肝病学
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干细胞生物学
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分子生物学
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基因组学
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DOI
PubMed
高影响因子
Genes & Diseases
·
2024
·
IF 6.9
Nan Wang,Xiaoyu Shen,Huakun Huang,Runhan Zhao,Habu Jiwa,Zongxin Li,Pei Li,Jixing Ye,Qiang Zhou
Amyloid precursor protein (APP), especially Swedish mutant APP (APPswe), is recognized as a significant pathogenic protein in Alzheimer's disease, but limited research has been conducted on the correlation between APPswe and the osteogenic differentiation of mesenchymal stem cells (MSCs). The effects of APPswe and its intracellular and extracellular segments on the osteogenic differentiation of bone morphogenetic protein 2 (BMP2)-induced MSCs were analyzed in this study. Our analysis of an existing database revealed that APP was positively correlated with the osteogenic differentiation of MSCs but negatively correlated with their proliferation and migration. Furthermore, APPswe promoted BMP2-induced osteogenic differentiation of MSCs, while APPswe-C (APPswe without an intracellular segment) had the opposite effect; thus, the intracellular domain of APPswe may be a key factor in promoting the osteogenic differentiation of MSCs. Additionally, both APPswe and APPswe-C inhibited the proliferation and migration of MSCs. Furthermore, the intracellular domain of APPswe inhibited the activity of the Notch pathway by regulating the expression of the Notch intracellular domain to promote the osteogenic differentiation of MSCs. Finally, APPswe-treated primary rat bone marrow MSCs exhibited the most favorable bone repair effect when a GelMA hydrogel loaded with BMP2 was used for in vivo experiments, while APPswe-C had the opposite effect. These findings demonstrate that APPswe promotes the osteogenic differentiation of MSCs by regulating the Notch pathway, but its extracellular segment blocks the self-renewal, proliferation, and migration of MSCs, ultimately leading to a gradual decrease in the storage capacity of MSCs and affecting long-term bone formation.
研究领域:
生物医学
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细胞生物学
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分子生物学
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DOI
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 10
·4248-4259
·
IF 5.251
Ruiying Huang,Jian Wang,Haoxiang Chen,Xuelei Shi,Xiaocheng Wang,Yonghua Zhu,Zhikai Tan
Injuries to the skin are common in daily life, and a certain type or size of defect is not easily restored using conventional dressings or naturally. The repair of these defects requires restoration of function in regenerated tissues. In this study, a tissue engineered skin was designed and fabricated using a bio-3D printing system. Polycaprolactone and bacterial cellulose comprised the scaffold, due to their excellent biocompatibility and multifunctionality. Adipose-derived mesenchymal stem cells (Ad-MSCs) were seeded onto the scaffold to functionalize it as an artificial skin. The finished artificial skin had mechanical properties similar to that of natural skin, and its fibrous structure providing a unique micro-environment that could regulate the paracrine function of the Ad-MSCs. This effect could be greatly increased by changes in the characteristics of the biomaterials. The artificial skin exhibited high biological activity, strong induction of cell recruitment, migration, growth and up-regulation of gene expression of relevant factors, resulting in excellent wound healing characteristics. This study clarified novel design aspects of cell-material interactions in which the topographical characteristics of materials can be further developed to establish cell signaling or communication networks that take advantage of the paracrine actions of Ad-MSCs to promote specific tissue regeneration or repair characteristics.
研究领域:
组织工程
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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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材料科学
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DOI
PubMed
高影响因子
Regenerative Therapy
·
2026
·
IF 4
Xianghui Mei,Dongchao Li,Li Sun,Zhen Wang,Houjian Ren,Hui Zhang,Min Ge,Defeng Wang,Qizhi Shuai
Introduction Mesenchymal stem cells (MSCs) hold significant potential for tissue repair and cell therapy. A primary obstacle in their application is the loss of stemness and onset of senescence during in vitro expansion, which compromises therapeutic efficacy. Plant-derived bioactive compounds like quercetin (Que) offer promise for enhancing MSC-based therapies; however, its poor aqueous solubility due to high lipophilicity and phenolic hydroxyl groups limits pharmaceutical utility. Methods To address this, we engineered homogeneous poly(lactic-co-glycolic acid) (PLGA) microspheres (hPLGA-Ms) using microfluidic technology to encapsulate hydrophobic Que, enabling its sustained release in physiological aqueous environments. Results The results showed the hPLGA-Ms loaded Que (Que/hPLGA-Ms) were uniform, well dispersed. The size of the hPLGA-Ms can be precisely controlled by adjusting the flow rates of two phases. Gene expression analysis demonstrated the hPLGA-Ms delivery of Que enhanced MSCs cellular viability, stemness, anti-senescence, secretion and migration abilities of cells. Conclusions In summary, the scalable and reproducible Que/hPLGA-Ms provide controlled release kinetics and significantly potentiate MSCs bioactivities. This delivery system represents a promising strategy for tissue engineering and regenerative therapies.
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高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Tengling Wu,Xiaoping Zhang,Yang Liu,Chunyan Cui,Yage Sun,Wenguang Liu
Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction (MI). However, the low retention of cells and drugs limits their therapeutic efficacies. Here, we propose a prefixed sponge carpet strategy, that is, aldehyde-dextran sponge (ODS) loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β [email protected] (HP-β [email protected] ) is first bonded to the rat's heart via capillary removal of interfacial water from the tissue surface, and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue. Then, an aqueous biocompatible hydrazided hyaluronic acid (HHA) solution encapsulating mesenchymal stem cells (MSCs) is impregnated into the anchored carpet to form [email protected] @HP-β [email protected] hydrogel in situ via click reaction, thus prolonging the in vivo retention time of therapeutic drug and cells. Importantly, the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface, avoiding adhesion to other tissues. The embedded HP-β [email protected] molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment, reduce cardiomyocyte apoptosis, and enhance the survival of transplanted MSCs, thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.
研究领域:
生物医学工程
·
心脏病学
·
干细胞生物学
·
药物递送系统
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 17
·2202904
·
IF 10
Yizuo Song,Xin Shou,Bo Sheng,Jie Mei,Keqing Shi,Luoran Shang,Xueqiong Zhu
Nanoparticles (NPs)-based drug carriers are effective in reducing systemic toxicity and drug resistance for chemotherapy, and an emerging trend focuses on integrating cell membranes with nanomedicines for tumor targeting. Mesenchymal stem cells (MSCs) are promising candidates due to their unique tropism toward cancer cells, yet the tumor-tropic abilities can differ for MSCs sourced from different tissues. Here, a multichannel microfluidic chip to screen different sourced MSCs with the greatest tropism toward cervical cancer cells is developed. Based on this, the cell membranes from the chorionic plate-derived MSC are isolated and membrane-camouflaged platinum prodrug composite NPs for cervical cancer treatment are prepared. Results demonstrate that the composite NPs can effectively target tumor sites and have a therapeutic effect both in vitro and in vivo. It is believed that the present microfluidic platform is a powerful tool for cell screening and tumor-on-a-chip studies, and the derived nanodelivery system represents the great value of cell membrane-camouflaged nanomedicine for targeted cancer therapy.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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干细胞生物学
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药学
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微流控技术
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DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Ze Lin,Yuan Xiong,Weilin Meng,Yiqiang Hu,Lili Chen,Lang Chen,Hang Xue,Adriana C. Panayi,Wu Zhou,Yun Sun,Faqi Cao,Guodong Liu,Liangcong Hu,Chenchen Yan,Xudong Xie,Chuanchuan Lin,Kaiyong Cai,Qian Feng,Bobin Mi,Guohui Liu
A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation. Over-active and continuous inflammation, however, impairs fracture healing and leads to excessive tissue damage. Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site. In the present study, we achieved an enriched concentration of PD-L1 from exosomes (Exos) of a genetically engineered Human Umbilical Vein Endothelial Cell (HUVECs), and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface, suppressing the activation of T cells. Furthermore, exosomal PD-L1 induced Mesenchymal Stem Cells (MSCs) towards osteogenic differentiation when pre-cultured with T cells. Moreover, embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner. Additionally, exosomal PD-L1, embedded in a hydrogel, markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase. Importantly, our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites, while T cells in distant immune organs such as the spleen were not affected. In summary, this study provides the first example of using PD-L1-enriched Exos for bone fracture repair, and highlights the potential of [email protected] systems for bone fracture therapy through immune inhibitory effects.
研究领域:
骨科
·
免疫学
·
再生医学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Qiuling Guo,Jingjing Chen,Qiqi Bu,Jinling Zhang,Minjie Ruan,Xiaoyu Chen,Mingming Zhao,Xiaolin Tu,Chengzhu Zhao
Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significance Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo . This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.
研究领域:
干细胞生物学
·
组织工程
·
再生医学
·
生物打印
·
骨再生
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Chuan Li,Liru Tian,Yihai Wang,Huan Luo,Jia Zeng,Peiqiang Su,Shulin Chen,Zhiheng Liao,Weimin Guo,Xiangjiu He,Shuqing Chen,Caixia Xu
Background Morinda officinalis (MO) is a herb used in Traditional Chinese Medicine (TCM) for the treatment of osteoporosis. M13, a MO-based anthraquinone compound is known to suppress osteoclast activity. However, whether M13 promotes MSCs osteogenic differentiation and its potential mechanism remains unknown. Purpose To examine the influence of M13 on MSCs proliferation and osteogenic differentiation and elucidate the underlying mechanism. Methods/Study designs The effect of M13 exposure on MSCs proliferation was assessed via CCK8 assay, clone formation assay, immunofluorescence, RT-qPCR, and Western blot. The M13-mediated osteogenesis in vitro and ex vivo were evaluated via ALP and Alizarin red S staining, osteogenesis-associated gene (Runx2, Col1a1 and Opn) expression, and fetal limb explants culture. Molecular docking was employed for target signal pathway screening. The potential signaling mechanisms of M13-promoted MSCs osteogenic differentiation were analyzed by introducing XAV939 (Wnt/β-catenin signaling inhibitor). Results M13 induced certain obvious positive effects on MSCs proliferation and osteogenic differentiation. Treatment with M13 enhanced MSCs viability and clone numbers. Meanwhile, M13 promoted osteogenic gene expression, enhanced ALP intensity and Alizarin red S staining in MSCs. In terms of mechanism, M13 strongly interacted with the docking site of the WNT signaling complex, thereby activating the Wnt/β-catenin pathway. Furthermore, the M13-mediated osteogenic effect was partially inhibited by XAV939 both in vitro and ex vivo , which confirmed that the Wnt/β-catenin axis is a critical regulator of M13-induced osteogenic differentiation of MSCs. Conclusion Our study elucidated for the first time that M13 significantly promoted osteogenic differentiation of MSCs via stimulation of the Wnt/β-catenin pathway in vitro and ex vivo .Our findings offered new additional evidence to support the MO or M13-based therapy of osteoporosis.
研究领域:
药理学
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细胞生物学
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分子生物学
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传统中药
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骨生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Jianchao Li,Ziyuan Guo,Zhenxv Wu,Yu Wang,Zongliang Wang,Min Guo,Peibiao Zhang
Microcarriers for large-scale cell culture have a broader prospect in cell screening compared with the traditional high cost, low efficiency, and cell damaging methods. However, the equal biological affinity to cells has hindered its application. Therefore, based on the antifouling strategy of zwitterionic polymer, we developed a cell-specific microcarrier (CSMC) for shielding non-target cells and capturing mesenchymal stem cells (MSCs), which has characteristics of high biocompatibility, low background noise and high precision. Briefly, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide and glycidyl methacrylate were grafted onto polygalacturonic acid, respectively. The former built a hydration layer through solvation to provide an excellent antifouling surface, while the latter provided active sites for the click reaction with sulfhydryl-modified cell-specific peptides, resulting in rapid immobilization of peptides. This method is applicable to the vast majority of polysaccharide materials. The accurate capture ratio of MSCs by CSMC in a mixed multicellular environment is >95 % and the proliferation rate of MSCs on microcarriers is satisfactory. In summary, this grafting strategy of bioactive components lays a foundation for the application of polysaccharide materials in the biomedical field, and the specific adhesive microcarriers also open up new ideas for the development of stem cell screening as well.
研究领域:
生物医学工程
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细胞生物学
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材料科学
·
干细胞研究
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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）